56 results on '"Nasheed Hossain"'
Search Results
2. Impact of cytogenetic abnormalities on outcomes of adult Philadelphia-negative acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation: a study by the Acute Leukemia Working Committee of the Center for International Blood and Marrow Transplant Research
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Aleksandr Lazaryan, Michelle Dolan, Mei-Jie Zhang, Hai-Lin Wang, Mohamed A. Kharfan-Dabaja, David I. Marks, Nelli Bejanyan, Edward Copelan, Navneet S. Majhail, Edmund K. Waller, Nelson Chao, Tim Prestidge, Taiga Nishihori, Partow Kebriaei, Yoshihiro Inamoto, Betty Hamilton, Shahrukh K. Hashmi, Rammurti T. Kamble, Ulrike Bacher, Gerhard C. Hildebrandt, Patrick J. Stiff, Joseph McGuirk, Ibrahim Aldoss, Amer M. Beitinjaneh, Lori Muffly, Ravi Vij, Richard F. Olsson, Michael Byrne, Kirk R. Schultz, Mahmoud Aljurf, Matthew Seftel, Mary Lynn Savoie, Bipin N. Savani, Leo F. Verdonck, Mitchell S. Cairo, Nasheed Hossain, Vijaya Raj Bhatt, Haydar A. Frangoul, Hisham Abdel-Azim, Monzr Al Malki, Reinhold Munker, David Rizzieri, Nandita Khera, Ryotaro Nakamura, Olle Ringdén, Marjolein van der Poel, Hemant S. Murthy, Hongtao Liu, Shahram Mori, Satiro De Oliveira, Javier Bolaños-Meade, Mahmoud Elsawy, Pere Barba, Sunita Nathan, Biju George, Attaphol Pawarode, Michael Grunwald, Vaibhav Agrawal, Youjin Wang, Amer Assal, Paul Castillo Caro, Yachiyo Kuwatsuka, Sachiko Seo, Celalettin Ustun, Ioannis Politikos, Hillard M. Lazarus, Wael Saber, Brenda M. Sandmaier, Marcos De Lima, Mark Litzow, Veronika Bachanova, Daniel Weisdorf, and Acute Leukemia Committee of the CIBMTR
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Cytogenetic risk stratification at diagnosis has long been one of the most useful tools to assess prognosis in acute lymphoblastic leukemia (ALL). To examine the prognostic impact of cytogenetic abnormalities on outcomes after allogeneic hematopoietic cell transplantation, we studied 1731 adults with Philadelphia-negative ALL in complete remission who underwent myeloablative or reduced intensity/non-myeloablative conditioning transplant from unrelated or matched sibling donors reported to the Center for International Blood and Marrow Transplant Research. A total of 632 patients had abnormal conventional metaphase cytogenetics. The leukemia-free survival and overall survival rates at 5 years after transplantation in patients with abnormal cytogenetics were 40% and 42%, respectively, which were similar to those in patients with a normal karyotype. Of the previously established cytogenetic risk classifications, modified Medical Research Council-Eastern Cooperative Oncology Group score was the only independent prognosticator of leukemia-free survival (P=0.03). In the multivariable analysis, monosomy 7 predicted post-transplant relapse [hazard ratio (HR)=2.11; 95% confidence interval (95% CI): 1.04-4.27] and treatment failure (HR=1.97; 95% CI: 1.20-3.24). Complex karyotype was prognostic for relapse (HR=1.69; 95% CI: 1.06-2.69), whereas t(8;14) predicted treatment failure (HR=2.85; 95% CI: 1.35-6.02) and overall mortality (HR=3.03; 95% CI: 1.44-6.41). This large study suggested a novel transplant-specific cytogenetic scheme with adverse [monosomy 7, complex karyotype, del(7q), t(8;14), t(11;19), del(11q), tetraploidy/near triploidy], intermediate (normal karyotype and all other abnormalities), and favorable (high hyperdiploidy) risks to prognosticate leukemia-free survival (P=0.02). Although some previously established high-risk Philadelphia-negative cytogenetic abnormalities in ALL can be overcome by transplantation, monosomy 7, complex karyotype, and t(8;14) continue to pose significant risks and yield inferior outcomes.
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- 2020
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3. Older patients with primary central nervous system lymphoma: Survival and prognostication across 20 <scp>U.S.</scp> cancer centers
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Kevin A. David, Suchitra Sundaram, Seo‐Hyun Kim, Ryan Vaca, Yong Lin, Samuel Singer, Mary‐Kate Malecek, Jordan Carter, Adam Zayac, Myung Sun Kim, Nishitha Reddy, Douglas Ney, Alma Habib, Christopher Strouse, Jerome Graber, Veronika Bachanova, Sidra Salman, Jean Alyxa Vendiola, Nasheed Hossain, Mazie Tsang, Ajay Major, David A. Bond, Prashasti Agrawal, Angel Mier‐Hicks, Pallawi Torka, Priya Rajakumar, Parameswaran Venugopal, Stephanie Berg, Michael Glantz, Samuel A. Goldlust, Matthew Folstad, Pallavi Kumar, Thomas A. Ollila, Johnny Cai, Stephen Spurgeon, Alex Sieg, Joseph Cleveland, Julie Chang, Narendranath Epperla, Reem Karmali, Seema Naik, Peter Martin, Sonali M. Smith, James Rubenstein, Brad Kahl, and Andrew M. Evens
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Hematology - Published
- 2023
4. EBV-positive PCNSL in older patients: incidence, characteristics, tumor pathology, and outcomes across a large multicenter cohort
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Prashasti Agrawal, Kevin A. David, Zhengming Chen, Suchitra Sundaram, Seo-Hyun Kim, Ryan Vaca, Yong Lin, Samuel Singer, Mary-Kate Malecek, Jordan Carter, Adam Zayac, Myung Sun Kim, Nishitha Reddy, Douglas Ney, Alma Habib, Christopher Strouse, Jerome Graber, Veronika Bachanova, Sidra Salman, Jean A. Vendiola, Nasheed Hossain, Mazie Tsang, Ajay Major, Maher K. Gandhi, Colm Keane, David A. Bond, Matthew Folstad, Julie Chang, Angel Mier-Hicks, Pallawi Torka, Priya Rajakumar, Parameswaran Venugopal, Stephanie Berg, Michael Glantz, Samuel A. Goldlust, Rahul Matnani, Pallavi Kumar, Thomas A. Ollila, Johnny Cai, Stephen E. Spurgeon, Alex G. Sieg, Joseph Cleveland, Narendranath Epperla, Reem Karmali, Seema Naik, Sonali M. Smith, James L. Rubenstein, Brad S. Kahl, Amy Chadburn, Andrew M. Evens, and Peter Martin
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Cancer Research ,Oncology ,Hematology - Published
- 2023
5. Maintenance therapy after second autologous hematopoietic cell transplantation for multiple myeloma. A CIBMTR analysis
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Liat Shargian-Alon, Moshe Yeshurun, Hira S. Mian, Hillard M. Lazarus, Shaji Kumar, Baldeep Wirk, Sagar S. Patel, Patrick Hagen, Sunita Nathan, Ricardo D. Parrondo, Naresh Bumma, Leona Holmberg, Mark A. Schroeder, Cindy Lee, Oren Pasvolsky, Nina Shah, Uri Rozovski, Saad Z. Usmani, Noel Estrada-Merly, Arnon Nagler, Trent P Wang, Taiga Nishihori, Muzaffar H. Qazilbash, Rahul Banerjee, Kevin C. Miller, Robert Peter Gale, Nasheed Hossain, Raphael Fraser, Amer Assal, and Anita D'Souza
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Oncology ,medicine.medical_specialty ,Transplantation, Autologous ,Article ,Bortezomib ,Maintenance therapy ,Median follow-up ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Autologous transplantation ,Lenalidomide ,Multiple myeloma ,Transplantation ,Univariate analysis ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,medicine.disease ,Pomalidomide ,Neoplasm Recurrence, Local ,Multiple Myeloma ,business ,medicine.drug - Abstract
The role of maintenance therapy after high-dose chemotherapy and first autologous transplantation in multiple myeloma (MM) is well established. We explored the effect of maintenance therapy on outcomes after salvage second autologous hematopoietic cell transplant (AHCT2) using the Center for International Blood and Marrow Transplant Research registry. Outcomes of interest included non-relapse mortality (NRM), relapse/progression (REL), progression-free and overall survival (PFS, OS). Of 522 patients who underwent AHCT2 between 2010 and 2018, 342 received maintenance therapy and 180 did not. Maintenance regimens included lenalidomide (42%), pomalidomide (13%), and bortezomib (13%). Median follow up was 58 months in the maintenance group and 61.5 months in the no-maintenance group. Univariate analysis showed superior outcomes at 5 years in maintenance compared to the no-maintenance group: NRM 2 (0.7-3.9)% vs 9.9 (5.9-14.9)%, (p < 0.01), REL 70.2 (64.4-75.8)% vs 80.3 (73.6-86.3)% (p < 0.01), PFS 27.8 (22.4-33.5)% vs. 9.8 (5.5-15.2)% (p < 0.01), and OS 54 (47.5-60.5)% vs 30.9 (23.2-39.2)% (p < 0.01), respectively. Use of maintenance therapy retained its association with improved outcomes in multivariate analysis. There was no difference in second cancers in the two groups (p = 0.39). We conclude that maintenance after AHCT2 is associated with improved 5-year outcomes.
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- 2021
6. Monitoring of Circulating Tumor DNA Improves Early Relapse Detection After Axicabtagene Ciloleucel Infusion in Large B-Cell Lymphoma: Results of a Prospective Multi-Institutional Trial
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Ilan R. Kirsch, Juliana Craig, Frederick L. Locke, Michael D. Jain, Allison P. Jacob, Lik Wee Lee, Jay Y. Spiegel, Matthew J. Frank, Ali Bukhari, Gursharan K. Claire, David B. Miklos, Katherine A. Kong, Aaron P. Rapoport, Erin Dean, Nasheed Hossain, Chelsea D. Mullins, Crystal L. Mackall, and Saurabh Dahiya
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Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,MEDLINE ,Early Relapse ,Circulating Tumor DNA ,Young Adult ,Text mining ,Refractory ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Young adult ,B-cell lymphoma ,Prospective cohort study ,Aged ,Biological Products ,business.industry ,ORIGINAL REPORTS ,Middle Aged ,medicine.disease ,Lymphoma ,Female ,Lymphoma, Large B-Cell, Diffuse ,Neoplasm Recurrence, Local ,business - Abstract
PURPOSE Although the majority of patients with relapsed or refractory large B-cell lymphoma respond to axicabtagene ciloleucel (axi-cel), only a minority of patients have durable remissions. This prospective multicenter study explored the prognostic value of circulating tumor DNA (ctDNA) before and after standard-of-care axi-cel for predicting patient outcomes. METHODS Lymphoma-specific variable, diversity, and joining gene segments (VDJ) clonotype ctDNA sequences were frequently monitored via next-generation sequencing from the time of starting lymphodepleting chemotherapy until progression or 1 year after axi-cel infusion. We assessed the prognostic value of ctDNA to predict outcomes and axi-cel–related toxicity. RESULTS A tumor clonotype was successfully detected in 69 of 72 (96%) enrolled patients. Higher pretreatment ctDNA concentrations were associated with progression after axi-cel infusion and developing cytokine release syndrome and/or immune effector cell–associated neurotoxicity syndrome. Twenty-three of 33 (70%) durably responding patients versus 4 of 31 (13%) progressing patients demonstrated nondetectable ctDNA 1 week after axi-cel infusion ( P < .0001). At day 28, patients with detectable ctDNA compared with those with undetectable ctDNA had a median progression-free survival and OS of 3 months versus not reached ( P < .0001) and 19 months versus not reached ( P = .0080), respectively. In patients with a radiographic partial response or stable disease on day 28, 1 of 10 patients with concurrently undetectable ctDNA relapsed; by contrast, 15 of 17 patients with concurrently detectable ctDNA relapsed ( P = .0001). ctDNA was detected at or before radiographic relapse in 29 of 30 (94%) patients. All durably responding patients had undetectable ctDNA at or before 3 months after axi-cel infusion. CONCLUSION Noninvasive ctDNA assessments can risk stratify and predict outcomes of patients undergoing axi-cel for the treatment of large B-cell lymphoma. These results provide a rationale for designing ctDNA-based risk-adaptive chimeric antigen receptor T-cell clinical trials.
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- 2021
7. Diffuse large B‐cell lymphoma with primary treatment failure: Ultra‐high risk features and benchmarking for experimental therapies
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Costa, Luciano J., Maddocks, Kami, Epperla, Narendranath, Reddy, Nishitha M., Karmali, Reem, Umyarova, Elvira, Bachanova, Veronika, Costa, Cristiana, Glenn, Martha J., Chavez, Julio C., Calzada, Oscar, Lansigan, Frederick, Nasheed, Hossain, Barta, Stefan K., Zhou, Zheng, Jaglal, Michael, Chhabra, Saurabh, HernandezIlizaliturri, Francisco, Xavier, Ana C., Mehta, Amitkumar, Peker, Deniz, ForeroTorres, Andreas, AlMansour, Zeina, Evens, Andrew M., Cohen, Jonathon B., Flowers, Christopher R., Fenske, Timothy S., and Hamadani, Mehdi
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- 2017
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8. Expanding the Toolbox of Adoptive Cell Immunotherapy
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Patrick J. Stiff and Nasheed Hossain
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Adoptive Cell Immunotherapy ,Internal medicine ,MEDLINE ,Medicine ,business ,Toolbox - Published
- 2021
9. COVID-19 thromboembolism incidence, risk factors, and anticoagulation practices from a Chicago metropolitan US population
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Stephanie Berg, Seo‐Hyun Kim, Amy Wozniak, Oluwatobi Odetola, Saad Arain, Ahmed Aleem, James Coggan, Ami Dave, Elizabeth Elliott, Ryan Guerrettaz, Hina Dalal, Raymond Lee, Abhigna Kodali, Patrick Moore, Sonam Patel, Priya Rajakumar, Shuai Qin, Glenda Delgado Ramos, Candice Schwartz, Fatema Esmail, Rebecca Feltman Frank, Ellen Murchie, Laura Pax, Nicole Yun, Yanyu Zhang, Kevin Barton, Patrick Hagen, Nasheed Hossain, Melissa L. Larson, Hanh Mai, Sucha Nand, Kathleen Phelan, Parameswawran Venugopal, Patrick Stiff, and Santosh Saraf
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Chicago ,Risk Factors ,Incidence ,Thromboembolism ,Anticoagulants ,COVID-19 ,Humans ,Hematology ,Venous Thromboembolism - Published
- 2022
10. Reduced intensity conditioning for acute myeloid leukemia using melphalan- vs busulfan-based regimens: a CIBMTR report
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Michael Byrne, Jane L. Liesveld, Richard F. Olsson, Sagar S. Patel, Hongtao Liu, Eric Wong, Brenda M. Sandmaier, Bipin N. Savani, Hannah Choe, Partow Kebriaei, Gulrayz Ahmed, Tania Jain, Moussab Damlaj, Rebecca L. Olin, Mehdi Hamadani, Uday R. Popat, Neil Palmisiano, Rajneesh Nath, Mei-Jie Zhang, Mark R. Litzow, Attaphol Pawarode, Mark P. Hertzberg, Taiga Nishihori, Arnon Nagler, Jean A. Yared, Mitchell S. Cairo, Ioannis Politikos, Michael R. Grunwald, Hisham Abdel-Azim, Usama Gergis, David A. Rizzieri, Baldeep Wirk, Ashish Bajel, Rammurti T. Kamble, Hemant S. Murthy, Jean-Yves Cahn, Corey Cutler, Mahmoud Aljurf, A. Samer Al-Homsi, Geoffrey L. Uy, Miguel-Angel Perales, Muhammad Waqas Khan, Miguel Angel Diaz, Minocher Battiwalla, Mohamed A. Kharfan-Dabaja, Nosha Farhadfar, Natasha Kekre, Vaibhav Agrawal, Hillard M. Lazarus, Jan Cerny, Rodrigo Martino, Nandita Khera, Youjin Wang, Asmita Mishra, Nasheed Hossain, Luis Isola, Leo F. Verdonck, Nirav N. Shah, Vijaya Raj Bhatt, Zachariah DeFilipp, Daniel J. Weisdorf, Vikram Mathews, Edward A. Copelan, Aaron T. Gerds, C. Esar O. Freytes, David Valc A. Arcel, Shahrukh K. Hashmi, Mrinal M. Patnaik, Sunita Nathan, Sachiko Seo, Marcos de Lima, Qaiser Bashir, David I. Marks, Zheng Zhou, Yoshihiro Inamoto, Ryotaro Nakamura, Hai-Lin Wang, Edmund K. Waller, James M. Foran, Gerhard C. Hildebrandt, Amer Assal, Zartash Gul, Hassan B. Alkhateeb, Ulrike Bacher, and Wael Saber
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Adult ,Melphalan ,medicine.medical_specialty ,Transplantation Conditioning ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Gastroenterology ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,610 Medicine & health ,Busulfan ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Total body irradiation ,medicine.disease ,Fludarabine ,Transplantation ,Leukemia, Myeloid, Acute ,Leukemia ,Alemtuzumab ,Erratum ,business ,medicine.drug - Abstract
There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival model was used with adjustment for patient, leukemia, and transplant-related factors. A total of 622 patients received FM and 791 received FB RIC. Compared with FB, the FM group had fewer transplant in complete remission (CR), fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab. More patients in the FM group received marrow grafts and had transplantation before 2005. OS was significantly lower within the first 3 months posttransplant in the FM group (hazard ratio [HR] = 1.82, P < .001), but was marginally superior beyond 3 months (HR = 0.87, P = .05). LFS was better with FM compared with FB (HR = 0.89, P = .05). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR = 3.85, P < .001). Long-term relapse was lower with FM (HR = 0.65, P < .001). Analysis restricted to patients with CR showed comparable results. In conclusion, compared with FB, the FM RIC showed a marginally superior long-term OS and LFS and a lower relapse rate. A lower OS early posttransplant within 3 months was largely the result of a higher early NRM.
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- 2020
11. Timing of allogeneic hematopoietic cell transplantation (alloHCT) for chronic myeloid leukemia (CML) patients
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Ayman Saad, Gregory A. Hale, Richard F. Olsson, Guillermo Garcia-Manero, Jane L. Liesveld, Farhad Ravandi, Kwang Woo Ahn, Sachiko Seo, Jan Cerny, Aaron T. Gerds, Michael R. Grunwald, Rammuriti T. Kamble, Taiga Nishihori, Melhem Solh, Xiao Lin, Srdan Verstovsek, Richard E. Champlin, Bipin N. Savani, Ronald Sobecks, Gorgun Akpek, Edwin P. Alyea, Mark R. Litzow, Celalettin Ustun, Hans C. Lee, Xuelin Huang, Andrew Daly, Mahmoud Aljurf, Ulrike Bacher, Hagop M. Kantarjian, Zachariah DeFilipp, Wael Saber, Jorge E. Cortes, Bei Hu, Tamila L. Kindwall-Keller, Bart L. Scott, Marcos de Lima, Nasheed Hossain, Uday R. Popat, Zhen-Huan Hu, Yoshihiro Inamoto, Mohamed A. Kharfan-Dabaja, David I. Marks, Jack W. Hsu, Rebecca S. S. Tidwell, Baldeep Wirk, and Elias Jabbour
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Oncology ,Cancer Research ,medicine.medical_specialty ,Hematopoietic cell ,business.industry ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Hematology ,respiratory tract diseases ,Transplantation ,03 medical and health sciences ,0302 clinical medicine ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,030220 oncology & carcinogenesis ,Internal medicine ,Leukemia, Myeloid, Chronic-Phase ,Humans ,Transplantation, Homologous ,Medicine ,Blast Crisis ,business ,030215 immunology - Abstract
While TKI are the preferred first-line treatment for chronic phase (CP) CML, alloHCT remains an important consideration. The aim is to estimate residual life expectancy (RLE) for patients initially diagnosed with CP CML based on timing of alloHCT or continuation of TKI in various settings: CP1 CML, CP2 + [after transformation to accelerated phase (AP) or blast phase (BP)], AP, or BP. Non-transplant cohort included single-institution patients initiating TKI and switched TKI due to failure. CIBMTR transplant cohort included CML patients who underwent HLA sibling matched (MRD) or unrelated donor (MUD) alloHCT. AlloHCT appeared to shorten survival in CP1 CML with overall mortality hazard ratio (HR) for alloHCT of 2.4 (95% CI 1.2-4.9
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- 2020
12. Maintenance Tyrosine Kinase Inhibitors Following Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Myelogenous Leukemia
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Ulrike Bacher, Wael Saber, Uday R. Popat, Amer Beitinjaneh, Richard Gopez Ancheta, Shahinaz M. Gadalla, Jean-Yves Cahn, Ying Liu, Michael R. Grunwald, Hillard M. Lazarus, Jeff Szer, Naeem Chaudhri, Hisham Abdel-Azim, Nasheed Hossain, Richard F. Olsson, Gerhard C. Hildebrandt, Melhem Solh, Ronald Sobecks, Jacob M. Rowe, Shahrukh K. Hashmi, Zhen-Huan Hu, Jack W. Hsu, Yoshihiro Inamoto, Aaron T. Gerds, Harry C. Schouten, Mohamed A. Kharfan-Dabaja, Muthalagu Ramanathan, Matt Kalaycio, Jane L. Liesveld, Jan Cerny, David S. Snyder, Zachariah DeFilipp, Taiga Nishihori, Mark B. Juckett, Celalettin Ustun, Andrew Daly, Ashish Bajel, Mahmoud Aljurf, Bipin N. Savani, Rammurti T. Kamble, Mehdi Hamadani, Kirk R. Schultz, Mark R. Litzow, Mary Lynn Savoie, Ran Reshef, Jean A. Yared, Siddhartha Ganguly, Robert Peter Gale, Sachiko Seo, Edwin P. Alyea, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, MUMC+: MA Hematologie (9), and Interne Geneeskunde
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Oncology ,Adult ,medicine.medical_specialty ,medicine.drug_class ,Maintenance ,medicine.medical_treatment ,Graft vs Host Disease ,Tyrosine kinase inhibitor ,Hematopoietic stem cell transplantation ,IMATINIB ,Tyrosine-kinase inhibitor ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,hemic and lymphatic diseases ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Medicine ,Humans ,Protein Kinase Inhibitors ,Transplantation ,chronic myeloid-leukemia ,therapy ,OUTCOMES ,Hematology ,allogeneic hematopoietic cell transplantation ,business.industry ,nilotinib prophylaxis ,Hematopoietic Stem Cell Transplantation ,Imatinib ,medicine.disease ,respiratory tract diseases ,Dasatinib ,chronic myelogenous leukemia ,Nilotinib ,030220 oncology & carcinogenesis ,Imatinib Mesylate ,business ,030215 immunology ,medicine.drug ,Chronic myelogenous leukemia - Abstract
It remains unknown whether the administration of tyrosine kinase inhibitors (TKIs) targeting BCR-ABL1 after allogeneic hematopoietic cell transplantation (HCT) is associated with improved outcomes for patients with chronic myelogenous leukemia (CML). In this registry study, we analyzed clinical outcomes of 390 adult patients with CML who underwent transplantation between 2007 and 2014 and received maintenance TKI following HCT (n = 89) compared with no TKI maintenance (n = 301), as reported to the Center for International Blood and Marrow Transplant Research. All patients received TKI therapy before HCT. The majority of patients had a disease status of first chronic phase at HCT (n = 240; 62%). The study was conducted as a landmark analysis, excluding patients who died, relapsed, had chronic graft-versus-host disease, or were censored before day +100 following HCT. Of the 89 patients who received TKI maintenance, 77 (87%) received a single TKI and the other 12 (13%) received multiple sequential TKIs. The most common TKIs used for maintenance were dasatinib (n = 50), imatinib (n = 27), and nilotinib (n = 27). As measured from day +100, the adjusted estimates for 5-year relapse (maintenance, 35% versus no maintenance, 26%; P = .11), leukemia-free survival (maintenance, 42% versus no maintenance, 44%; P = .65), or overall survival (maintenance, 61% versus no maintenance, 57%; P = .61) did not differ significantly between patients receiving TKI maintenance or no maintenance. These results remained unchanged in multivariate analysis and were not modified by disease status before transplantation. In conclusion, our data from this day +100 landmark analysis do not demonstrate a significant impact of maintenance TKI therapy on clinical outcomes. The optimal approach to TKI administration in the post-transplantation setting in patients with CML remains undetermined. (C) 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
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- 2020
13. First Late Effect in Pediatric Survivors with Chronic Graft-Versus-Host Disease Following Hematopoietic Cell Transplantation for Hematologic Malignancy
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Peiman Hematti, Daniel R. Couriel, Sagar S. Patel, Minoo Battiwalla, Lazaros J. Lekakis, Sanghee Hong, Catherine J. Lee, Jeffery J. Auletta, Scott R. Solomon, Leo F. Verdonck, Mukta Arora, Joseph Pidala, Margaret L. MacMillan, Shahinaz M. Gadalla, Shahrukh K. Hashmi, Hasan Hashem, Karen Chen, Stephen R. Spellman, Yoshihiro Inamoto, Sherif M. Badawy, Zachariah DeFilipp, Vijaya Raj Bhatt, Nasheed Hossain, Anita J. Kumar, Rammurti T. Kamble, Tao Wang, Miguel Angel Diaz, Carrie L. Kitko, Robert Peter Gale, Nosha Farhadfar, David Buchbinder, Bipin N. Savani, Dipenkumar Modi, Akshay Sharma, and Jean-Yves Cahn
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Oncology ,Transplantation ,medicine.medical_specialty ,Hematopoietic cell ,business.industry ,Late effect ,Cell Biology ,Hematology ,medicine.disease ,Graft-versus-host disease ,Internal medicine ,Hematologic malignancy ,medicine ,Molecular Medicine ,Immunology and Allergy ,medicine.symptom ,business - Published
- 2021
14. Umbilical Cord Blood as an Alternate Donor Sources for High Risk Elderly Patients Undergoing Allogeneic Stem Cell Transplantation for Hematological Malignancies
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Patrick Hagen, Shuai Qin, Scott Smith, William H. Adams, Patrick J. Stiff, Nasheed Hossain, Stephanie B. Tsai, Loredana Campo, and Shruti Singh
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education.field_of_study ,medicine.medical_specialty ,business.industry ,Population ,medicine.disease ,Umbilical cord ,Gastroenterology ,Transplantation ,Leukemia ,medicine.anatomical_structure ,Graft-versus-host disease ,Cord blood ,Internal medicine ,Cohort ,medicine ,Progression-free survival ,business ,education - Abstract
Allogeneic stem cell transplantation remains the only curative option for many hematological malignancies. Umbilical cord blood (UCB) is an alternate donor source with potentially increased morbidity in elderly patients. We evaluated outcomes in alternate donor sources, prior to the initiation of haploidentical transplantation at our institution, of matched unrelated donor (MUD) and UCB in elderly patients (mean age 64, range 60-75). One hundred and eighty-four patients were included (MRD: 57; MUD: 69; UCB: 58). There was no difference in acute or chronic graft versus host disease among donor sources (all p > .05). In this high-risk population, 128 (70%) had either a high disease risk index or high (>2) comorbidity index. Median progression free survival (PFS) was lowest among UCB (5.5 months; 95% CI 2.8-9.4) and MUD (5.6 months; 95% CI 3.7-17.7) as compared to MRD (18.3 months; 95% CI 8.4-64.8). On multivariable analysis, the rate of mortality was higher for UCB than MRD patients (1.88, 95% CI 1.04 – 3.37), but there was no difference between UCB and MUD (p = .61) or between MUD and MRD (p = .25). Conclusions were similar for PFS. Our experience shows that even in this high-risk elderly cohort, UCB continues to be a viable alternate donor source.
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- 2021
15. Real World Outcomes of Sars-Cov-2 Thrombosis Rates across Three University Health Systems in the Chicago Metropolitan Area
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Diana Kreppel, Stephanie Berg, Katie W. Phelan, Sonam Patel, Yanyu Zhang, Patrick J. Stiff, Kevin Barton, Hanh P. Mai, Elizabeth Elliott, Shuai Qin, Glenda Delgado-Ramos, Nicholas Torgerson, Candice Schwartz, Abhigna Kodali, Erin M. Lowery, Priya Rajakumar, Santosh L. Saraf, Patrick Hagen, Melissa L. Larson, Oluwatobi Odetola, Amy Wozniak, Tracie Watson, Seo-Hyun Kim, James Coggan, Laura Pax, Ahmed Aleem, Rebecca Feltman Frank, Nasheed Hossain, Raymond W. Lee, Patrick Moore, Sucha Nand, Ryan Guerrettaz, Fatema Esmail, Hina Dalal, Ellen Murchie, Saad Arain, Daulath Singh, and Anthi Katsouli
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medicine.medical_specialty ,education.field_of_study ,Multivariate analysis ,business.industry ,Deep vein ,Incidence (epidemiology) ,Immunology ,Population ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Thrombosis ,Pulmonary embolism ,Exact test ,medicine.anatomical_structure ,904.Outcomes Research-Non-Malignant Conditions ,Internal medicine ,Cohort ,Medicine ,business ,education - Abstract
Introduction: Initial studies from Wuhan, China reported patients infected with SARS-CoV-2 have uncontrolled coagulopathy and an increased risk for thrombotic complications, including pulmonary embolism (PE), deep vein thrombosis (DVT), and arterial thrombosis.1 The incidence of thrombosis attributed to coronavirus disease 2019 (COVID-19) ranged from 9.5% in all hospital-admitted patients to 31% in the critically ill.2,3 COVID-19 has had a major impact on the Chicago metropolitan area with over 121,000 confirmed cases as of August 2020, Cook county being the 4th highest affected county after Maricopa, Miami-Dade and Los Angeles counties.4 The primary goal of this study is to describe the rate of thrombotic events in the Chicago metropolitan area, highlighting an ethnically diverse population, and identify new risk factors for thrombosis between three university health systems. Methods: We conducted a retrospective analysis between three university health systems in the Chicago metropolitan area: Loyola University Health System (LUHS): comprised of one tertiary and two community hospitals, Rush University System for Health (RUSH): comprised of one tertiary and two community hospitals, and University of Illinois-Chicago (UIC): a tertiary hospital. All patients had positive SARS-CoV-2 testing and were hospitalized for COVID-19. PE, DVT or arterial thrombosis were confirmed by supportive imaging modalities. Wilcoxon rank sum test were used to test the associations of continuous variables; Chi-square test or Fisher's exact test were used to test the associations of categorical variables. All analyses were performed with SAS 9.4 and two-sided p-value < .05 were deemed statistically significant. Results: Between March and May 2020, 2,180 patients from LUHS, RUSH and UIC were hospitalized for COVID-19 and were included in our analysis. Baseline patient demographics are described in Table 1. Race/ethnicity demographics are as follows: Hispanics (H)/ African Americans (AA) represented 47%/17% of LUHS patients, 32%/42% of RUSH patients, and 36%/51% of UIC patients, respectively (Figure 1). Intensive care admissions were needed in 33% of all patients. Documented total thrombotic events are as follows: LUHS = 5.4% (41 VTE/PE, 10 arterial and 5 with both venous and arterial); RUSH = 9.7% (70 VTE/PE, 7 arterial and 4 with both venous/arterial); UIC = 6% (14 VTE/PE, 4 arterial and 0 with both venous/arterial). Patients that developed a thrombotic event were similar by age, sex, and BMI to those without a thrombotic event. Anticoagulation prophylaxis was given to 82% of pts at LUHS and UIC at time of admission. Collectively, those with thrombotic events (N=156) had higher incidence of intensive care admission, elevated white blood cell (WBC) count and a d-dimer >5X upper limit normal (ULN) at presentation. Furthermore, a higher proportion of pts that had a thrombotic event were diabetic at LUHS and RUSH (Table 2). Mortality in COVID-19 patients was 13-16% and patients that had a thrombotic event had a higher risk of death in the RUSH and UIC cohorts. Conclusions: In a racially diverse, multi-institutional cohort of patients, we demonstrate that 7.2% of COVID-19 patients had a thrombotic event. Consistent risk factors for thrombosis across the different centers included an initial d-dimer levels >5X ULN, elevated initial WBC count, diabetes, and being critically ill. Mortality differences and anticoagulation practices between the institutions as well as race/ethnicity differences regarding thrombosis will be explored in future combined multivariate analyses. Finally, based off these risk factors, identification of patients at most risk for thrombosis is needed to reduce the morbidity and mortality when diagnosed with COVID-19. References -Tang et. al. J Thromb Haemost. 2020;18:844-847. -Klock et. Al. Thrombosis Research 2020;191:145-147. -Al-Samkari H, Laef RS, Dzik WH et. Al. COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection. Blood. 2020;136(4):489-500. -https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/county-map.html; accessed 8/7/20. Disclosures Arain: Astellas: Other: Spouse is employed. Stiff:Macrogenics: Research Funding; Delta-Fly: Research Funding; Unum: Research Funding; Atara: Research Funding; Kite, a Gilead Company: Research Funding; Amgen: Research Funding; Gamida Cell: Research Funding. Saraf:Novartis, Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other: Advisory Boards, Speakers Bureau; Pfizer, Global Blood Therapeutics, Novartis: Research Funding.
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- 2021
16. CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial
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Steven A. Feldman, Kara L. Davis, John H. Baird, Robert Lowsky, Rachel C. Lynn, Magali Bazzano, Judith A. Shizuru, Matthew J. Frank, Surbhi Sidana, Maria Caterina Rotiroti, Maria Iglesias, Sean Mackay, Sally Arai, Bita Sahaf, Shabnum Patel, Nirali N. Shah, Laura Johnston, Jay Y. Spiegel, Jing Zhou, Juliana Craig, Robert S. Negrin, Robbie G. Majzner, Andrew R. Rezvani, Zach Ehlinger, Ilan R. Kirsch, Parveen Shiraz, Chelsea D. Mullins, Michael G. Ozawa, Nikolaos Gkitsas, Crystal L. Mackall, Terry J. Fry, Warren D. Reynolds, Yasodha Natkunam, Sneha Ramakrishna, Scott J. Bornheimer, Allison P. Jacob, Lori Muffly, Jean Oak, Haiying Qin, Katherine A. Kong, Wen-Kai Weng, Everett Meyer, Nasheed Hossain, John S. Tamaresis, Sheren F. Younes, David B. Miklos, Liora M. Schultz, Eric J Yang, and Harshini Chinnasamy
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0301 basic medicine ,Oncology ,Adult ,medicine.medical_specialty ,Lymphoma, B-Cell ,Lymphoma ,medicine.medical_treatment ,Sialic Acid Binding Ig-like Lectin 2 ,Antigens, CD19 ,Cancer immunotherapy ,Immunotherapy, Adoptive ,General Biochemistry, Genetics and Molecular Biology ,CD19 ,Article ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,immune system diseases ,Recurrence ,Phase I trials ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Humans ,B-cell lymphoma ,B cell ,Aged ,Acute lymphocytic leukaemia ,biology ,business.industry ,General Medicine ,Immunotherapy ,Middle Aged ,medicine.disease ,Chimeric antigen receptor ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,biology.protein ,Disease Progression ,business ,Progressive disease - Abstract
Despite impressive progress, more than 50% of patients treated with CD19-targeting chimeric antigen receptor T cells (CAR19) experience progressive disease. Ten of 16 patients with large B cell lymphoma (LBCL) with progressive disease after CAR19 treatment had absent or low CD19. Lower surface CD19 density pretreatment was associated with progressive disease. To prevent relapse with CD19− or CD19lo disease, we tested a bispecific CAR targeting CD19 and/or CD22 (CD19-22.BB.z-CAR) in a phase I clinical trial (NCT03233854) of adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) and LBCL. The primary end points were manufacturing feasibility and safety with a secondary efficacy end point. Primary end points were met; 97% of products met protocol-specified dose and no dose-limiting toxicities occurred during dose escalation. In B-ALL (n = 17), 100% of patients responded with 88% minimal residual disease-negative complete remission (CR); in LBCL (n = 21), 62% of patients responded with 29% CR. Relapses were CD19−/lo in 50% (5 out of 10) of patients with B-ALL and 29% (4 out of 14) of patients with LBCL but were not associated with CD22−/lo disease. CD19/22-CAR products demonstrated reduced cytokine production when stimulated with CD22 versus CD19. Our results further implicate antigen loss as a major cause of CAR T cell resistance, highlight the challenge of engineering multi-specific CAR T cells with equivalent potency across targets and identify cytokine production as an important quality indicator for CAR T cell potency., Bispecific CAR T cells targeting CD19 and CD22 exhibit clinical activity and low toxicity in patients with large B cell lymphoma and B cell acute lymphoblastic leukemia, with relapses associated with loss of CD19 but not CD22.
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- 2020
17. Myeloablative Conditioning for Allogeneic Transplantation Results in Superior Disease-Free Survival for Acute Myelogenous Leukemia and Myelodysplastic Syndromes with Low/Intermediate but not High Disease Risk Index: A Center for International Blood and Marrow Transplant Research Study
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Neil Palmisiano, Reinhold Munker, Siddhartha Ganguly, Wael Saber, Hillard M. Lazarus, Miguel Angel Diaz, Attaphol Pawarode, Taiga Nishihori, Partow Kebriaei, Jan Cerny, Jean-Yves Cahn, Nasheed Hossain, Sunita Nathan, Baldeep Wirk, Sachiko Seo, Melhem Solh, Brenda M. Sandmaier, Christopher Bredeson, Nelli Bejanyan, Gregory A. Hale, Jakob Passweg, Edward A. Copelan, Harry C. Schouten, Cesar O. Freytes, Hai-Lin Wang, David A. Rizzieri, Biju George, Daniel J. Weisdorf, Natasha Kekre, Michael R. Grunwald, Stefan O. Ciurea, Marcos de Lima, Sergio Giralt, Vera Ulrike Bacher, Marjolein van der Poel, Richard F. Olsson, Michael Byrne, Rodrigo Martino, Mark R. Litzow, Khalid Bo-Subait, Jean A. Yared, Mei-Jie Zhang, Christopher S. Hourigan, Christopher G. Kanakry, Bipin N. Savani, Mitchell S. Cairo, Gerhard C. Hildebrandt, Erica D. Warlick, Robert Peter Gale, Mohamed A. Kharfan-Dabaja, Steven D. Gore, Claudio G. Brunstein, Leo F. Verdonck, Ajoy Dias, Mahmoud Aljurf, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, MUMC+: MA Hematologie (9), and Interne Geneeskunde
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Oncology ,Transplantation Conditioning ,IMPACT ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,0302 clinical medicine ,AML ,hemic and lymphatic diseases ,MDS ,Immunology and Allergy ,Medicine ,610 Medicine & health ,Myeloablative ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Leukemia ,Leukemia, Myeloid, Acute ,030220 oncology & carcinogenesis ,WORKING PARTY ,Molecular Medicine ,REDUCED-INTENSITY ,Adult ,medicine.medical_specialty ,Allogeneic transplantation ,ACUTE MYELOID-LEUKEMIA ,REGIMENS ,Disease-Free Survival ,Article ,03 medical and health sciences ,Myelogenous ,Internal medicine ,Humans ,Transplantation, Homologous ,TERM-FOLLOW-UP ,Aged ,Retrospective Studies ,Transplantation ,MUTATIONS ,business.industry ,Myelodysplastic syndromes ,RIC ,STEM-CELL TRANSPLANTATION ,Cell Biology ,medicine.disease ,UNRELATED DONOR TRANSPLANTATION ,Myelodysplastic Syndromes ,DRI ,business ,030215 immunology - Abstract
Compared with reduced-intensity conditioning (RIC), myeloablative conditioning (MAC) is generally associated with lower relapse risk after allogeneic hematopoietic cell transplantation (HCT) for acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). However, disease-specific risk factors in AML/MDS can further inform when MAC and RIC may yield differential outcomes. We analyzed HCT outcomes stratified by the Disease Risk Index (DRI) in 4387 adults (age 40 to 65 years) to identify the impact of conditioning intensity. In the low/ intermediate-risk DRI cohort, RIC was associated with lower nonrelapse mortality (NRM) (hazard ratio [HR],.74; 95% confidence interval [CI],.62 to.88; P
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- 2020
18. Outcomes of rituximab-BEAM vs BEAM conditioning regimen in patients with diffuse large B-cell lymphoma undergoing autologous transplantation
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Taiga Nishihori, Yizeng He, Ulrike Bacher, Timothy S. Fenske, Kwang Woo Ahn, Navneet S. Majhail, Deepa Jagadeesh, Narendranath Epperla, Nosha Farhadfar, Mohamed A. Kharfan-Dabaja, Praveen Ramakrishnan Geethakumari, Mehdi Hamadani, Jan Cerny, Rammurti T. Kamble, Sherif M. Badawy, Carlos Litovich, Bradley M. Haverkos, Robert Peter Gale, Nasheed Hossain, Alberto Mussetti, Sairah Ahmed, Jean A. Yared, Sunita Nathan, Mahmoud Aljurf, Richard F. Olsson, Hillard M. Lazarus, Hemant S. Murthy, Anna Sureda, Bipin N. Savani, David J. Inwards, Lazaros J. Lekakis, Matthew Mei, Vaishalee P. Kenkre, Cesar O. Freytes, Aleksandr Lazaryan, Mitchell S. Cairo, and Nelli Bejanyan
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Male ,Melphalan ,Oncology ,Cancer Research ,Transplantation Conditioning ,Cohort Studies ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Registries ,Treatment Failure ,030212 general & internal medicine ,610 Medicine & health ,Etoposide ,Aged, 80 and over ,Cytarabine ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,Treatment Outcome ,030220 oncology & carcinogenesis ,Female ,Rituximab ,Lymphoma, Large B-Cell, Diffuse ,medicine.drug ,Adult ,medicine.medical_specialty ,Transplantation, Autologous ,Article ,Young Adult ,03 medical and health sciences ,Chemoimmunotherapy ,Internal medicine ,Humans ,Autologous transplantation ,Aged ,business.industry ,medicine.disease ,Carmustine ,Survival Analysis ,Transplantation ,Multivariate Analysis ,business ,Diffuse large B-cell lymphoma - Abstract
BACKGROUND Although rituximab-based high-dose therapy is frequently used in diffuse large B cell lymphoma (DLBCL) patients undergoing autologous hematopoietic cell transplantation (auto-HCT), data supporting the benefits are not available. Herein, we report the impact of rituximab-based conditioning on auto-HCT outcomes in patients who have DLBCL. METHODS Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, 862 adult DLBCL patients undergoing auto-HCT between 2003 and 2017 using BEAM (BCNU, etoposide, cytarabine, melphalan) conditioning regimen were included. All patients received frontline rituximab-containing chemoimmunotherapy and had chemosensitive disease pre-HCT. Early chemoimmunotherapy failure was defined as not achieving complete remission (CR) after frontline chemoimmunotherapy or relapse within 1 year of initial diagnosis. The primary outcome was overall survival (OS). RESULTS The study cohort was divided into 2 groups: BEAM (n = 667) and R-BEAM (n = 195). On multivariate analysis, no significant difference was seen in OS (P = .83) or progression-free survival (PFS) (P = .61) across the 2 cohorts. No significant association between the use of rituximab and risk of relapse (P = .15) or nonrelapse mortality (P = .12) was observed. Variables independently associated with lower OS included older age at auto-HCT (P
- Published
- 2020
19. Circulating tumor DNA assessment in patients with diffuse large B-cell lymphoma following CAR T-cell therapy
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Katherine A. Kong, Saurabh Dahiya, Armen M. Abramian, Ryan Le, David B. Miklos, Nasheed Hossain, and Lori Muffly
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Cancer Research ,medicine.medical_treatment ,Immunotherapy, Adoptive ,CD19 ,Circulating Tumor DNA ,03 medical and health sciences ,0302 clinical medicine ,Positron Emission Tomography Computed Tomography ,Biomarkers, Tumor ,Humans ,Medicine ,In patient ,biology ,business.industry ,Hematology ,Immunotherapy ,medicine.disease ,Chimeric antigen receptor ,Lymphoma ,Treatment Outcome ,Oncology ,Circulating tumor DNA ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,CAR T-cell therapy ,Lymphoma, Large B-Cell, Diffuse ,business ,Diffuse large B-cell lymphoma ,030215 immunology - Abstract
With the recent FDA approval of Kite Pharmaceuticals CD19 targeting Chimeric Antigen Receptor (CAR) T-cell therapy (KTE-C19, Axicabtagene ciloleucel, Yescarta, Kite Pharma—a subsidiary of Gilead, F...
- Published
- 2018
20. Outcomes of Medicare-age eligible NHL patients receiving RIC allogeneic transplantation: a CIBMTR analysis
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Sairah Ahmed, Nelli Bejanyan, Veronika Bachanova, Andy I. Chen, Stefan O. Ciurea, Kwang Woo Ahn, Zachariah DeFilipp, Andrew R. Rezvani, Timothy S. Fenske, Alex F. Herrera, Minoo Battiwalla, Mehdi Hamadani, Hillard M. Lazarus, Hemant S. Murthy, Leona Holmberg, Javier Bolaños-Meade, Anita D'Souza, Nirav N. Shah, Edmund K. Waller, Anna Sureda, Bipin N. Savani, Parastoo B. Dahi, Matthew L. Ulrickson, Nasheed Hossain, Narendranath Epperla, Nosha Farhadfar, Mohamed A. Kharfan-Dabaja, Carlos Litovich, Sonali M. Smith, Vaishalee P. Kenkre, Bradley M. Haverkos, and Taiga Nishihori
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medicine.medical_specialty ,Transplantation Conditioning ,Cancer cells ,Multivariate analysis ,Allogeneic transplantation ,Databases, Factual ,Medicare ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Survival analysis ,Aged ,Transplantation ,business.industry ,Lymphoma, Non-Hodgkin ,Age Factors ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,medicine.disease ,Survival Analysis ,United States ,Malaltia de Hodgkin ,Lymphoma ,030220 oncology & carcinogenesis ,Cord blood ,Cohort ,Cèl·lules canceroses ,Hodgkin's disease ,business ,DISEASE RELAPSE ,030215 immunology - Abstract
The application of allogeneic hematopoietic cell transplantation (allo-HCT) in non-Hodgkin lymphoma (NHL) patients ≥65 years in the United States is limited by lack of Medicare coverage for this indication. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we report allo-HCT outcomes of NHL patients aged ≥65 years (older cohort; n = 446) compared with a cohort of younger NHL patients aged 55-64 years (n = 1183). We identified 1629 NHL patients undergoing a first reduced-intensity conditioning (RIC) or nonmyeloablative conditioning allo-HCT from 2008 to 2015 in the United States. Cord blood or haploidentical transplants were excluded. The median age was 68 years (range 65-77) for the older cohort vs 60 years (range 55-64) in the younger cohort. The 4-year adjusted probabilities of nonrelapse mortality (NRM), relapse/progression (R/P), progression-free survival (PFS), and overall survival (OS) of the younger and older groups were 24% vs 30% (P = .03), 41% vs 42% (P = .82), 37% vs 31% (P = .03), and 51% vs 46% (P = .07), respectively. Using multivariate analysis, compared with the younger group, the older cohort was associated with increased NRM, but there was no difference between the 2 cohorts in terms of R/P, PFS, or OS. The most common cause of death was disease relapse in both groups. In NHL patients eligible for allo-HCT, there was no difference in OS between the 2 cohorts. Age alone should not determine allo-HCT eligibility in NHL, and Medicare should expand allo-HCT coverage to older adults.
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- 2018
21. Impact of Chronic Graft-Versus-Host Disease on First Late Effect Among Adult Survivors of Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research (CIBMTR) Analysis
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Lazaros J. Lekakis, Nosha Farhadfar, Sanghee Hong, Stephen R. Spellman, Dipenkumar Modi, Carrie L. Kitko, Joseph Pidala, Vijaya Raj Bhatt, Miguel Angel Diaz, Shahrukh K. Hashmi, Akshay Sharma, Tao Wang, Robert Peter Gale, Minoo Battiwalla, Nasheed Hossain, Shahinaz M. Gadalla, Anita J. Kumar, Catherine J. Lee, Mukta Arora, Sherif M. Badawy, Zachariah DeFilipp, Rammurti T. Kamble, Margaret L. MacMillan, Karen Chen, Yoshihiro Inamoto, Jeffery J. Auletta, Peiman Hematti, David Buchbinder, Hasan Hashem, Leo F. Verdonck, Jean-Yves Cahn, Daniel R. Couriel, Sagar S. Patel, Bipin B. Savani, and Scott R. Solomon
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Oncology ,Transplantation ,medicine.medical_specialty ,Hematopoietic cell ,business.industry ,Late effect ,Cell Biology ,Hematology ,medicine.disease ,Graft-versus-host disease ,Bone transplantation ,Internal medicine ,Molecular Medicine ,Immunology and Allergy ,Medicine ,medicine.symptom ,business - Published
- 2021
22. Time to Complete Response after Defibrotide Initiation in Hepatic Veno-Occlusive Disease: Is Less Actually More?
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Patrick Hagen and Nasheed Hossain
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Veno-occlusive ,medicine.medical_specialty ,Hepatic veno-occlusive disease ,Defibrotide ,Hepatic Veno-Occlusive Disease ,Article ,obstruction syndrome ,Polydeoxyribonucleotides ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Complete response ,Transplantation ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematopoietic cell ,Cell Biology ,Hematology ,medicine.disease ,Cardiology ,Molecular Medicine ,disease/sinusoidal ,business ,medicine.drug - Abstract
Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication that occurs after hematopoietic cell transplantation (HCT). The mortality associated with untreated VOD/SOS with multiorgan dysfunction (MOD) has been reported to be >80%. The recommended dose of defibrotide is 6.25 mg/kg every 6 hours, administered as a 2-hour i.v. infusion, for a minimum of 21 days or until resolution of VOD/SOS signs and symptoms. The objective of this analysis was to evaluate the time to complete response (CR) in patients with post-HCT VOD/SOS treated with defibrotide. The time to defibrotide discontinuation due to a CR served as a surrogate for time to CR in an expanded access study (T-IND; ClinicalTrials.gov NCT00628498; n = 1000), and was analyzed separately from the time to CR data pooled from a phase 2 randomized dose-finding study (NCT00003966; n = 74 patients who received 25 mg/kg/day) and a phase 3 historically controlled study (NCT00358501; n = 102). For all studies, a CR was defined as total serum bilirubin 21 days). Taken together, these results highlight the importance of continued defibrotide therapy until resolution of VOD/SOS signs and symptoms, as currently indicated in the approved product labels, which may occur beyond the recommended minimum of 21 days.
- Published
- 2021
23. Correction to: Impact of depth of clinical response on outcomes of acute myeloid leukemia patients in first complete remission who undergo allogeneic hematopoietic cell transplantation
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Amer Beitinjaneh, Nelson J. Chao, Jakob Passweg, Ajoy Dias, Nosha Farhadfar, Robert Peter Gale, Jong Wook Lee, Miguel Angel Diaz, Partow Kebriaei, Corey Cutler, Tim Prestidge, Taiga Nishihori, Neil Palmisiano, Reinhold Munker, Haydar Frangoul, Witold B. Rybka, Michael Byrne, Lohith Gowda, Hemant S. Murthy, Cesar O. Freytes, Mahmoud Aljurf, Hai-Lin Wang, Elihu H. Estey, Jane L. Liesveld, Rammurti T. Kamble, Sherif M. Badawy, Mohamed A. Kharfan-Dabaja, Christopher G. Kanakry, Nasheed Hossain, Ankit Kansagra, Sunita Nathan, Kirk R. Schultz, Saurabh Chhabra, Kehinde Adekola, Richard F. Olsson, Siddhartha Ganguly, Hongtao Liu, David A. Rizzieri, Sachiko Seo, Leo F. Verdonck, Mark R. Litzow, O Ringdén, Mei-Jie Zhang, Brenda M. Sandmaier, Marjolein van der Poel, Joseph P. McGuirk, Daniel J. Weisdorf, Jean A. Yared, Marcos de Lima, Roger Strair, Vijaya Raj Bhatt, Mary Lynn Savoie, Richard J. Lin, Michael R. Grunwald, Paul Castillo, Mary Elizabeth Percival, Jean-Yves Cahn, Zachariah DeFilipp, Akshay Sharma, Melhem Solh, Maxwell M. Krem, Edward A. Copelan, Nelli Bejanyan, Hisham Abdel-Azim, Hillard M. Lazarus, Ulrike Bacher, Wael Saber, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, and MUMC+: MA Hematologie (9)
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Oncology ,medicine.medical_specialty ,Neoplasm, Residual ,Bone marrow transplantation ,Disease ,Article ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,610 Medicine & health ,Retrospective Studies ,Transplantation ,Hematopoietic cell ,Marrow transplantation ,business.industry ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,Complete remission ,Myeloid leukemia ,Hematology ,Prognosis ,Confidence interval ,Leukemia, Myeloid, Acute ,Cohort ,business - Abstract
Acute myeloid leukemia (AML) patients often undergo allogeneic hematopoietic cell transplantation (alloHCT) in first complete remission (CR). We examined the effect of depth of clinical response, including incomplete count recovery (CRi) and/or measurable residual disease (MRD), in patients from the Center for International Blood and Marrow Transplantation Research (CIBMTR) registry. We identified 2492 adult patients (1799 CR and 693 CRi) who underwent alloHCT between January 1, 2007 and December 31, 2015. The primary outcome was overall survival (OS). Multivariable analysis was performed to adjust for patient-, disease-, and transplant-related factors. Baseline characteristics were similar. Patients in CRi compared to those in CR had an increased likelihood of death (HR: 1.27; 95% confidence interval: 1.13-1.43). Compared to CR, CRi was significantly associated with increased non-relapse mortality (NRM), shorter disease-free survival (DFS), and a trend toward increased relapse. Detectable MRD was associated with shorter OS, shorter DFS, higher NRM, and increased relapse compared to absence of MRD. The deleterious effects of CRi and MRD were independent. In this large CIBMTR cohort, survival outcomes differ among AML patients based on depth of CR and presence of MRD at the time of alloHCT. Further studies should focus on optimizing post-alloHCT outcomes for patients with responses less than CR.
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- 2021
24. C-MYC-positive relapsed and refractory, diffuse large B-cell lymphoma: Impact of additional 'hits' and outcomes with subsequent therapy
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Michael Jaglal, Nishitha Reddy, Luciano J. Costa, Narendranath Epperla, Jonathon B. Cohen, Mehdi Hamadani, Cristiana A Costa, Elvira Umyarova, Andrew J. Evans, Frederick Lansigan, Nasheed Hossain, Martha Glenn, Veronika Bachanova, Stefan K. Barta, Mohammed Salhab, Ana C. Xavier, Zheng Zhou, Francisco J. Hernandez-Ilizaliturri, Saurabh Chhabra, Reem Karmali, Christopher R. Flowers, Amitkumar Mehta, Julio C. Chavez, Kami J. Maddocks, Timothy S. Fenske, Zeina Al-Mansour, and Oscar Calzada
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Hazard ratio ,Salvage therapy ,Cancer ,Retrospective cohort study ,medicine.disease ,Lymphoma ,Surgery ,Transplantation ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,Chemoimmunotherapy ,hemic and lymphatic diseases ,030220 oncology & carcinogenesis ,Internal medicine ,Cohort ,medicine ,business ,030215 immunology - Abstract
BACKGROUND The impact of MYC proto-oncogene, basic helix-loop-helix (MYC) translocations (with or without additional rearrangements involving the B-cell lymphoma 2 [BCL2] or BCL6 genes) on the response to salvage therapy and survival in patients with diffuse large B-cell lymphoma (DLBCL) who experience primary treatment failure is not well defined. METHODS This was a multicenter, retrospective study of the impact of MYC, BCL2, and BCL6 rearrangements in patients with DLBCL who failed to achieve complete remission or relapsed within 6 months after they completed upfront chemoimmunotherapy. RESULTS The authors examined response to salvage therapy, receipt of hematopoietic cell transplantation (HCT), and survival outcomes in MYC-negative (n = 120), MYC-positive single hit (SH) (n = 20), and MYC-positive double hit/triple hit (DH/TH) (n = 35) cohorts. The overall response rate in these cohorts to first salvage therapy (51%, 50%, and 54%, respectively) and receipt of HCT (52%, 40%, and 43%, respectively) were comparable between the 3 cohorts. The 2-year overall survival rate was 29.9% in the MYC-negative cohort, 0% in the MYC-positive SH cohort, and 9.9% in the MYC-positive DH/TH cohort (P < .001), and no difference was observed between the SH and DH/TH cohorts (P = .8). The higher risk of death for patients with MYC-positive SH DLBCL (hazard ratio, 1.70; 95% confidence interval, 0.98-2.96; P = .06) and those with MYC-positive DH/TH DLBCL (hazard ratio, 2.22; 95% confidence interval, 1.41-3.50; P = .001) persisted after adjusting for covariates. For patients who underwent autologous HCT, the 2-year overall survival rate was 55.4% in the MYC-negative cohort, 0% in the MYC-positive SH cohort, and 19.4% in the MYC-positive DH/TH cohort (P < .001). All 4 MYC-positive patients who underwent allogeneic HCT relapsed in
- Published
- 2017
25. A Single-Center, Retrospective Study, of Risk Factors for Clostridium Difficile Infection Among Allogeneic Hematopoietic Stem Cell Transplant Recipients
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Cara Joyce, Patrick Hagen, Christine M. Thomas, Scott E. Smith, Stephanie B. Tsai, Sonam Patel, Stephanie Berg, Patrick J. Stiff, Zahra Ismail, and Nasheed Hossain
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Transplantation ,education.field_of_study ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Incidence (epidemiology) ,Population ,Immunosuppression ,Retrospective cohort study ,Hematology ,Odds ratio ,Single Center ,Cord blood ,Internal medicine ,Medicine ,Infection control ,business ,education - Abstract
Introduction Clostridium difficile infection (CDI) is a leading cause of hospital-acquired infection. Allogeneic hematopoietic stem cell transplant (aHSCT) recipients in the peri-transplant periods represent an especially vulnerable population due to chronic immunosuppression, prolonged hospital stays, and routine use of antibiotics (abx). Previous attempts to identify potential risk factors (RF) for CDI are inconsistent in the literature. Objectives Our study goals are to describe CDI incidence, associated risk factors, and CDI characteristics in our own aHSCT population. Study results will be utilized in designing future infection prevention strategies and to promote abx stewardship. Methods We retrospectively evaluated all aHSCT recipients between Jan 2011-May 2017 at Loyola University Cardinal Bernardin Cancer Center. Inclusion criteria included age >18, 1st aHSCT, and hematological malignancy. Both myeloablative and non-myeloablative conditioning regimens were included. Disease risk was defined by the ASBMT classification. RF for CDI included comorbid conditions, proton pump inhibitor (PPI) and abx use during the 1st 100 days after aHSCT, and development of acute (aGVHD) and chronic (cGVHD) graft vs host disease. Data pertaining to CDI classification was collected. aGVHD was graded based on the International BMT Registry System and cGVHD per the NIH consensus criteria. The peri-transplant period evaluated included 6 months prior to 2 years following aHSCT. Logistic regression analysis was performed to estimate adjusted odds ratios for factors associated with development of CDI. Results A total of 322 patients (pt) met our inclusion criteria, of which 89 (27.6%) developed CDI, 55 pts were classified as severe or severe-complicated per ACG criteria and 18 (20.2%) had recurrence within 60 days. Graft type consisted of 109 (33.9%) allogeneic matched related, 124 (38.5%) matched unrelated and 89 (27.6%) cord blood. This was a high risk group with most pts having either intermediate (60.1%) or high/very high (31.5%) disease risk. Infections were common, as 225 (69.9%) pts developing an infection during the 1st 100 days after aHSCT. In multivariable analysis, cord blood graft source (OR=1.99, 95% CI: 1.05-3.8, p = 0.036), PPI use (OR=2.02, 95% CI: 1.08-3.8 p = 0.028), and chronic GI GVHD (OR =5.86, 95% CI: 1.64-20.98, p = 0.018) were associated with increased odds of CDI. Lastly, female sex (OR=0.4, 95% CI: 0.25-0.78, p = 0.005) and GI tract infection (including hepatobiliary source) in first 100 days after HSCT (OR=0.41, 95% CI: 0.17-0.98 p=0.045) were associated with decreased odds of CDI. Of note, rates of II-IV aGVHD were low (N=49, 15%). Conclusion Our population had 27% incidence of CDI and we note that cord blood graft, PPI use, GI cGVHD were associated with increased risk for CDI. These findings may have important implications for the supportive care plans for aHSCT pts.
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- 2020
26. Liposomal Daunorubicin/Cytarabine As a Bridge to Second Allogeneic Transplant for Early Relapses after First Allograft for Acute Myelogenous Leukemia/Myelodysplastic Syndrome
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Stephanie B. Tsai, Patrick Hagen, Scott E. Smith, Nasheed Hossain, Daulath Singh, and Patrick J. Stiff
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Melphalan ,Transplantation ,medicine.medical_specialty ,Allogeneic transplantation ,business.industry ,Hematology ,medicine.disease ,Gastroenterology ,Tacrolimus ,Fludarabine ,Liposomal daunorubicin ,Leukemia ,Internal medicine ,medicine ,Cytarabine ,business ,Busulfan ,medicine.drug - Abstract
Introduction Liposomal daunorubicin/cytarabine (Vyxeos® or lipo-CD) is a dual drug liposomal encapsulation, delivering these drugs at a fixed 1:5 synergistic ratio for a longer therapeutic period. Compared to standard 7+3, lipo-CD pts had improved survival and remission rates in a pivotal phase III study, with more reaching allogeneic transplantation (HCT), with lower post-HCT mortality and improved survival. With its enhanced pharmacokinetics, lipo-CD may provide a potent bridge to second transplant for early relapses after HCT. Here, we report our experience. Methods We retrospectively reviewed recipients of lipo-CD at our institution since FDA approval 8/2017. Of 23 pts, 8 relapsed Results Median age was 60 yrs. They received 1-4 lines of therapy (median 2) prior to first HCT with 5/8 pts having received 7+3 (cytarabine 100-200mg/m2 × 7 days + dauno 60-90mg/m2 × 3 days). 6 had adverse cytogenetics/genomic profiles. 7/8 had AML and 1 high grade MDS. Pts relapsed at 2 to 7 mo (median 4 mo) after first HCT, and all 8 received full lipo-CD induction (dauno 44 mg/m2 and cytarabine 100 mg/m2 on Days 1, 3, and 5) as outpatient therapy. [Table] 7/8 had Day 14 bone marrow biopsies: 3 were clear, 2 had >80% cytoreduction, and 2 had similar blast count. 3 with persistent disease underwent re-induction with lipo-CD (Days 1 and 3). All successfully proceeded to second transplant at 15-70 days after lipo-CD: 7 with same donor after melphalan 140mg/m2, and 1 from a different donor after busulfan/fludarabine. Tacrolimus was started on day + 7 and discontinued at day + 28 if no GVHD. 4/8 remain alive. 2 relapsed at 3 and 6 months post-HCT and are remarkably in CR at 19 and 16 mo after second transplant despite isolated CNS relapses, which were successfully treated. The other two relapsed at 2 and 3 mo post-HCT and are alive after second transplant. Conclusion Outpatient lipo-CD as a bridge to second transplant is feasible and effective in treating AML/MDS with early relapse after first HCT. While preliminary, survival appears favorable to that reported (14-23% at 1 year) in this very poor risk group, including those with adverse cytogenetics. Prospective multi-center trials are planned.
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- 2020
27. Late Events After CD-19 CAR-T Treatment
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Nasheed Hossain and Michael I. Nishimura
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Oncology ,Transplantation ,medicine.medical_specialty ,Receptors, Chimeric Antigen ,business.industry ,T-Lymphocytes ,Antigens, CD19 ,MEDLINE ,Hematology ,Immunotherapy, Adoptive ,Text mining ,Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ,Internal medicine ,medicine ,Humans ,Lymphoma, Large B-Cell, Diffuse ,Car t cells ,business - Published
- 2020
28. Outcomes of haploidentical vs matched sibling transplantation for acute myeloid leukemia in first complete remission
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Hisham Abdel-Azim, Reinhold Munker, Wael Saber, Jean-Yves Cahn, Melhem Solh, Gerhard C. Hildebrandt, Joseph Pidala, Taiga Nishihori, Robert Peter Gale, Richard F. Olsson, Brian C. Shaffer, Hillard M. Lazarus, Sachiko Seo, Miguel Angel Diaz, Yener Koc, O Ringdén, Mahmoud Aljurf, Hemant S. Murthy, Mark R. Litzow, Neil Palmisiano, Brenda M. Sandmaier, Corey Cutler, John L. Wagner, Andrew Daly, Jacob M. Rowe, Sagar S. Patel, Anurag K. Singh, Keith Stockerl-Goldstein, Nasheed Hossain, Amer Beitinjaneh, Shahrukh K. Hashmi, Mohamed A. Kharfan-Dabaja, Nandita Khera, Javier Bolaños-Meade, Leo F. Verdonck, Nelli Bejanyan, Nosha Farhadfar, Asad Bashey, Michael R. Grunwald, Theresa Hahn, Sunita Nathan, Marcos de Lima, Edward A. Copelan, David A. Rizzieri, Betul Oran, Daniel J. Weisdorf, Rebecca L. Olin, Mehdi Hamadani, Ryotaro Nakamura, Ashish Bajel, Michael Byrne, Kirk R. Schultz, Jong Wook Lee, Siddhartha Ganguly, Armin Rashidi, Christopher G. Kanakry, Hai-Lin Wang, Edmund K. Waller, Amer Assal, Stefan O. Ciurea, Mei-Jie Zhang, Mitchell S. Cairo, Minoo Battiwalla, Rodrigo Martino, Vijaya Raj Bhatt, Joseph P. McGuirk, Mary Lynn Savoie, H. Kent Holland, Johan Maertens, and Rizwan Romee
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Male ,Transplantation Conditioning ,Myeloid ,Graft vs Host Disease ,Blood Donors ,Gastroenterology ,Recurrence ,immune system diseases ,QUALITY-OF-LIFE ,hemic and lymphatic diseases ,POSTTRANSPLANTATION CYCLOPHOSPHAMIDE ,Bone Marrow Transplantation ,Incidence ,Remission Induction ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Hematology ,Middle Aged ,EUROPEAN-SOCIETY ,Leukemia, Myeloid, Acute ,Leukemia ,medicine.anatomical_structure ,surgical procedures, operative ,WORKING PARTY ,SURVIVAL ,Female ,Life Sciences & Biomedicine ,STEM-CELLS ,Immunosuppressive Agents ,medicine.drug ,Adult ,medicine.medical_specialty ,endocrine system ,Adolescent ,Cyclophosphamide ,BONE-MARROW ,Calcineurin Inhibitors ,Disease-Free Survival ,HEMATOPOIETIC-CELL TRANSPLANTATION ,Young Adult ,Internal medicine ,medicine ,Humans ,Survival analysis ,Aged ,Retrospective Studies ,CORD-BLOOD TRANSPLANTATION ,Transplantation ,Science & Technology ,business.industry ,Siblings ,medicine.disease ,Survival Analysis ,UNRELATED DONOR TRANSPLANTATION ,Graft-versus-host disease ,Chronic Disease ,Transplantation, Haploidentical ,business - Abstract
HLA-haploidentical hematopoietic cell transplantation (Haplo-HCT) using posttransplantation cyclophosphamide (PT-Cy) has improved donor availability. However, a matched sibling donor (MSD) is still considered the optimal donor. Using the Center for International Blood and Marrow Transplant Research database, we compared outcomes after Haplo-HCT vs MSD in patients with acute myeloid leukemia (AML) in first complete remission (CR1). Data from 1205 adult CR1 AML patients (2008-2015) were analyzed. A total of 336 patients underwent PT-Cy-based Haplo-HCT and 869 underwent MSD using calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis. The Haplo-HCT group included more reduced-intensity conditioning (65% vs 30%) and bone marrow grafts (62% vs 7%), consistent with current practice. In multivariable analysis, Haplo-HCT and MSD groups were not different with regard to overall survival (P = .15), leukemia-free survival (P = .50), nonrelapse mortality (P = .16), relapse (P = .90), or grade II-IV acute GVHD (P = .98). However, the Haplo-HCT group had a significantly lower rate of chronic GVHD (hazard ratio, 0.38; 95% confidence interval, 0.30-0.48; P < .001). Results of subgroup analyses by conditioning intensity and graft source suggested that the reduced incidence of chronic GVHD in Haplo-HCT is not limited to a specific graft source or conditioning intensity. Center effect and minimal residual disease-donor type interaction were not predictors of outcome. Our results indicate a lower rate of chronic GVHD after PT-Cy-based Haplo-HCT vs MSD using calcineurin inhibitor-based GVHD prophylaxis, but similar other outcomes, in patients with AML in CR1. Haplo-HCT is a viable alternative to MSD in these patients. ispartof: BLOOD ADVANCES vol:3 issue:12 pages:1826-1836 ispartof: location:United States status: published
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- 2019
29. Lower Graft-versus-Host Disease and Relapse Risk in Post-Transplant Cyclophosphamide-Based Haploidentical versus Matched Sibling Donor Reduced-Intensity Conditioning Transplant for Hodgkin Lymphoma
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Kwang Woo Ahn, Baldeep Wirk, Miguel-Angel Perales, Alex F. Herrera, Hemant S. Murthy, Javier Bolaños-Meade, Pashna N. Munshi, Rodrigo Martino, Abraham S. Kanate, Nasheed Hossain, Ana Sureda, Yago Nieto, Umar Farooq, Nilanjan Ghosh, Vera Ulrike Bacher, Nelli Bejanyan, Sairah Ahmed, Jennifer A. Kanakry, Timothy S. Fenske, Hisham Abdel-Azim, Alberto Mussetti, Sachiko Seo, Mahmoud Aljurf, David J. Inwards, Rizwan Romee, Jonathon B. Cohen, Jean A. Yared, Carlos Litovich, Mehdi Hamadani, Ephraim J. Fuchs, and Bipin N. Savani
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Oncology ,Adult ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,Cyclophosphamide ,Adolescent ,Graft vs Host Disease ,Disease-Free Survival ,Article ,immune system diseases ,Recurrence ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Clinical endpoint ,Humans ,610 Medicine & health ,Aged ,Transplantation ,business.industry ,Siblings ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Hematology ,Odds ratio ,Middle Aged ,medicine.disease ,Allografts ,Hodgkin Disease ,Confidence interval ,Tissue Donors ,Calcineurin ,Survival Rate ,Graft-versus-host disease ,Female ,business ,medicine.drug - Abstract
Classic Hodgkin lymphoma (cHL) patients with relapsed or refractory disease may benefit from allogeneic hematopoietic cell transplantation (allo-HCT), but many lack a matched sibling donor (MSD). Herein, we compare outcomes of 2 reduced-intensity conditioning (RIC) HCT platforms in cHL: T cell-replete related donor haploidentical (haplo) HCT with a post-transplant cyclophosphamide (PTCy)-based approach versus an MSD/calcineurin inhibitor (CNI)-based approach. The study included 596 adult patients who underwent a first RIC allo-HCT for cHL between 2008 and 2016 using either a haplo-PTCy (n = 139) or MSD/CNI-based (n = 457) approach. Overall survival (OS) was the primary endpoint. Secondary endpoints included acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD), nonrelapse mortality (NRM), relapse/progression, and progression-free survival (PFS). On multivariate analysis, there was no significant difference between haplo/PTCy and MDS/CNI-based approaches in terms of OS (hazard ratio [HR], 1.07; 95% confidence interval [CI], .79 to 1.45; P = .66) or PFS (HR, .86; 95% CI, .68 to 1.10; P = .22). Haplo/PTCy was associated with a significantly higher risk of grades II to IV aGVHD (odds ratio [OR], 1.73, 95% CI, 1.16 to 2.59; P = .007), but the risk of grades III to IV aGVHD was not significantly different between the 2 cohorts (OR, .61; 95% CI, .29 to 1.27; P = .19). The haplo/PTCy platform provided a significant reduction in cGVHD risk (HR, .45; 95% CI, .32 to .64; P < .001), and a significant reduction in relapse risk (HR, .74; 95% CI, .56 to .97; P = .03). There was a statistically nonsignificant trend toward higher NRM with a haplo/PTCy approach (HR, 1.65; 95% CI, .99 to 2.77; P = .06). Haplo/PTCy-based approaches are associated with lower incidences of cGVHD and relapse, with PFS and OS outcomes comparable with MSD/CNI-based approaches. There was a leaning toward higher NRM with a haplo/PTCy-based platform. These data show that haplo/PTCy allo-HCT in cHL results in survival comparable with MSD/CNI-based allo-HCT.
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- 2019
30. The Use of a Fitbit Physical Activity Monitor Device Among Patients Undergoing Hematopoietic Stem Cell Transplantation (HSCT)
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Michael Wesolowski, Patrick J. Stiff, Sarah Mooney, Stephanie B. Tsai, Nancy Porter, Elizabeth Simmons, Patricia B. Mumby, Scott Smith, Sarah Thilges, Allison Davis, Patrick Hagen, and Nasheed Hossain
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Oncology ,Transplantation ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Physical activity ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,Internal medicine ,medicine ,Molecular Medicine ,Immunology and Allergy ,business - Published
- 2021
31. Impact of immunoparesis on clinical outcomes following bone marrow transplantation
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Nicholas Torgerson, Patrick Hagen, Oluwatobi Odetola, Stephanie B. Tsai, Scott E. Smith, Nasheed Hossain, and Patrick J. Stiff
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Oncology ,Cancer Research ,medicine.medical_specialty ,Bone marrow transplantation ,business.industry ,Internal medicine ,medicine ,In patient ,Newly diagnosed ,medicine.disease ,business ,Multiple myeloma - Abstract
e20505 Background: Immunoparesis (hypogammaglobinemia) has been shown to impact outcomes in patients with newly diagnosed multiple myeloma (MM). Its impact in the post-transplant setting and potential risk of both infections and immune dysregulation impacting relapse is less clear. We sought to assess the role of immunoparesis both pre and post autologous stem cell transplant (ASCT) in newly diagnosed MM patients. Our primary outcome was the impact of immunoparesis on progression free survival (PFS) post-ASCT controlling for maintenance therapy. Methods: We evaluated all MM patients between 2008 and 2017 at Loyola University who underwent ASCT. Inclusion criteria included first ASCT and age > 18 years. We evaluated both the presence of and number of impacted immunoglobulin (Ig) classes pre-transplant and day 100, 6-months, and 12 months post-ASCT. Results: The most common MM isotype was IgG Kappa (41.01%). Immunoparesis pre-ASCT and post-ASCT at day 100, 6 months, and 12 months was seen in 75%, 89.5%, 80%, and 58.5% respectively. Median time from diagnosis to transplant was 7.75 months (5.98 – 13.73). When adjusting for pre-transplant response, conditioning regimen, and post-transplant maintenance, neither the absolute presence of or number of Ig-classes impacting was predictive of hazard of disease progression or death (OS) while ISS-stage, best response post ASCT, and time from diagnosis to transplant were (table). Conclusions: Contrary to studies in the pre-transplant setting, our analysis indicates that immunoparesis is not predictive of relapse or survival in the post-transplant setting, suggesting modification of disease process with treatment and ASCT. When controlled for maintenance therapy, immunoparesis does not increase risk of progression or decrease overall survival alleviating the concern for increased morbidity/mortality secondary to infections in the face of immunoparesis in the era of maintenance therapy. [Table: see text]
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- 2020
32. Liposomal Daunorubicin/Cytarabine As a Bridge to Donor Lymphocyte Infusion or Allogeneic Stem Cell Transplantation for High-Risk Acute Myelogenous Leukemia
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Patrick Hagen, Patrick J. Stiff, Scott E. Smith, Daulath Singh, Stephanie B. Tsai, and Nasheed Hossain
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Oncology ,medicine.medical_specialty ,business.industry ,Daunorubicin ,Immunology ,Cell Biology ,Hematology ,ThioTEPA ,Biochemistry ,Donor lymphocyte infusion ,Liposomal daunorubicin ,Fludarabine ,Transplantation ,Internal medicine ,medicine ,Cytarabine ,business ,Busulfan ,medicine.drug - Abstract
Introduction: Liposomal daunorubicin/cytarabine (Vyxeos®) is a dual drug liposomal encapsulation of cytarabine and daunorubicin, delivering drugs at a fixed 5:1 synergistic ratio for a longer therapeutic period. Compared to standard 7+3, liposomal cytarabine/daunorubicin (lipo-cytara/dauno) patients had improved survival and remission rates in a pivotal phase III study of elder adults with high-risk acute myelogenous leukemia (AML). Furthermore, more lipo-cytara/dauno patients went to allogeneic stem cell transplantation (HCT), with lower mortality and improved survival compared to those induced with 7+3. With its enhanced pharmacokinetics, lipo-cytara/dauno may provide a potent bridge to transplant. We report our experience using lipo-cytara/dauno as a bridge to same donor lymphocyte infusion (DLI) or different donor HCT in high-risk AML. Methods: We retrospectively reviewed all patients who received lipo-cytara/dauno at our institution since the FDA approval in August 2017. Of the 21 patients who have been treated, 9 received it as a bridge to cell therapy. All patients received the drug by usual means under the FDA label. Results: The median age of the 9 patients who received lipo-cytara/dauno as a bridge to cell therapy was 59 years. Seven were male, and two were female. Patients had had 1-4 prior lines of chemotherapy (median 2) with 7 of 9 patients having received prior standard 7+3 induction (cytarabine 100-200 mg/m2 x 7 days infusion and daunorubicin 60-90 mg/m2 x 3 days). Most had adverse cytogenetics, and all 9 patients received full lipo-cytara/dauno induction (daunorubicin 44 mg/m2 and cytarabine 100 mg/m2 on Days 1, 3, and 5) as outpatient therapy [Table]. Of the 9 patients, 6 had AML with very early relapse after HCT, with median time to relapse of 4 months (range 3 to 7 months). All 6 successfully proceeded to their planned cell infusion: 5 received same donor DLI after melphalan at 140 mg/m2, and 1 underwent second HCT from a different donor with busulfan/fludarabine conditioning at Days 15-40 after lipo-cytara/dauno. Of the remaining 3, two had relapsed AML after an initial remission (one was in first complete remission (CR1) for 3 months after 7+3/midostaurin induction and the other was in CR1 for 7 months after 7+3 induction/high dose cytarabine consolidation) and one had primary refractory disease (PREF) after 7+3 and azacitidine/venetoclax induction regimens. All 3 successfully underwent first HCT at Days 15-100 days after lipo-cytara/dauno bridge. The PREF patient received fludarabine/cyclophosphamide/TBI conditioning followed by matched unrelated donor transplant. Of the 2 with relapsed AML after initial remission, one received busulfan/fludarabine/thiotepa conditioning followed by umbilical cord stem cell transplantation and the other patient received fludarabine/cyclophosphamide/TBI conditioning prior to matched related donor transplant. Six of 9 had Day 14 bone marrow biopsies after lipo-cytara/dauno: 2 were in CR, 2 had >80% cytoreduction, and 2 had similar blast count. Three with persistent disease underwent reinduction with lipo-cytara/dauno (Days 1 and 3) and proceeded straight to cell therapy after. Median days to hospitalization after outpatient lipo-cytara/dauno was 6 days (range 3 to 14 days). Four out of 9 patients remain alive. Two were very early post HCT relapses (relapsed at 3 and 6 months post-HCT), both of which are remarkably in CR at 14 and 17 months after second cell therapy. Interestingly, both had CNS relapse, which were successfully treated, and both remain alive and in remission today. The other two had relapsed AML and PREF AML and underwent first HCT after lipo-cytara/dauno bridge. They remain alive and in remission at 1 and 8 months. Conclusion: In this retrospective study, outpatient lipo-cytara/dauno as a bridge to cell therapy is feasible and effective in very high-risk AML with no other viable options. While preliminary, survival appears favorable to that reported elsewhere at 14-23% at 1 year in this poor risk group, including those with adverse cytogenetic and/or very early post-HCT relapse. Prospective multi-center trials are planned to further evaluate lipo-cytara/dauno as a bridge to DLI/HCT in those with early relapse post-HCT and in those with refractory disease, with therapy to include CNS prophylaxis. Disclosures Stiff: Gilead/Kite Pharma: Consultancy, Honoraria, Research Funding; Amgen: Research Funding; Gamida-Cell: Research Funding; Incyte: Research Funding; Cellectar: Research Funding; Unum: Research Funding. Tsai:Jazz pharmaceuticals: Speakers Bureau; Jazz pharmaceuticals: Consultancy.
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- 2019
33. Phase I Trial Using CD19/CD22 Bispecific CAR T Cells in Pediatric and Adult Acute Lymphoblastic Leukemia (ALL)
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Anne Cunniffe Marcy, Terry J. Fry, Bita Sahaf, Kara L. Davis, Crystal L. Mackall, Juliana Craig, Michelle Fujimoto, Lori Muffly, Haiying Qin, Katherine A. Kong, Nasheed Hossain, Jay Y. Spiegel, Jenny Sumin Yoon, David B. Miklos, Robbie G. Majzner, Liora M. Schultz, Emily Egeler, Neehar Bhatia, Sneha Ramakrishna, Meena Kadapakkam, Christina Baggott, Courtney Erickson, Sharon Mavroukakis, Everett Meyer, Matthew J. Frank, Shabnum Patel, and Steven A. Feldman
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Oncology ,medicine.medical_specialty ,Cyclophosphamide ,business.industry ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Fludarabine ,Leukemia ,medicine.anatomical_structure ,Internal medicine ,Acute lymphocytic leukemia ,medicine ,Adult Acute Lymphoblastic Leukemia ,Blinatumomab ,Bone marrow ,business ,medicine.drug - Abstract
Introduction: Chimeric antigen receptor (CAR) T cells targeting either CD19 or CD22 have yielded striking complete remission (CR) rates of 70%-90% in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL), but CD19 negative and CD22 low relapse limits the curative potential of these single-antigen CAR T cell approaches. We hypothesized that a bivalent CAR-T construct that can target CD19 and/or CD22 would prevent antigen negative/low relapse. Here we present the combined single institution experience to date of pediatric and adult patients with R/R ALL treated with this novel bispecific CAR. Methods: We conducted parallel Phase I clinical trials of CD19/CD22 bispecific CAR T cells in pediatric and adult patients with relapsed/refractory ALL. We utilized lentiviral transduction of a bivalent CAR construct incorporating the fmc63 CD19 and m971 CD22 single chain variable fragments (scFvs) and a 41BB costimulatory endodomain. After lymphodepletion with fludarabine and cyclophosphamide, patients were infused with fresh or cryopreserved CAR T cells manufactured using a 7-11 day process. Two dose levels were tested during dose escalation: Dose level 1 was 1x106 CAR T cells/kg and dose level 2 was 3x106 cells/kg. Primary objectives assessed the ability to successfully manufacture CAR19/22 CAR T cells and safety while response at Day 28 post-infusion was a secondary objective. Blood, bone marrow and cerebrospinal fluid samples were obtained at protocol defined intervals for correlative biology studies. Results: Nineteen patients have been enrolled (10 pediatric; 9 adult) with a median age of 23 years (range, 2-68) and median of 4 (range, 2-11) prior lines of leukemia-directed therapy. Ten patients received prior HCT, 9 were treated with prior Blinatumomab, 3 with prior CD19 directed CAR T cells and 4 with prior Inotuzumab. Fourteen patients (8 pediatric, 6 adult) have been infused to date with CD19/CD22 bispecific CAR T cells; 7 were treated at dose level 1 (DL1) and 7 at dose level 2 (DL2). Successful manufacturing of cells at target dose levels was achieved in all patients. Twelve patients have reached day 28 and are included in the safety and response analysis presented here. Nine of 12 (75%) experienced cytokine release syndrome (CRS) and 2/12 (17%) developed immune-effector cell neurotoxicity syndrome (ICANS). The CRS and ICANS were all grade 1 or 2 across both dose levels and across pediatric and adult patients except for one adult with high disease burden who experienced grade 4 CRS and grade 4 ICANS, both of which were reversible. No differences in toxicities were seen across the patient age spectrum and there were no cases of treatment-related mortality within 28 days following CAR T infusion. Eleven of 12 (92%) patients achieved a CR, 10 of whom achieved CR at day 28 and one with a PR of extramedullary disease at day 28 which improved to CR by day 180 without further leukemia-directed intervention. One patient had primary progressive disease prior to day 28. Peak CAR expansion as detected by peripheral blood flow cytometry reached a median level of 11.13% (DL1) and 29.1% (DL2) CAR T of CD3+ cells with a range of 0.7-22.54% and 3.8-86.96%, respectively. To date, 3 patients (1 pediatric and 2 adult patients) have relapsed, all with retention of CD19. Post-remission practice differed across pediatric and adult patients; Six pediatric patients reaching day 28 underwent consolidative hematopoietic cell transplantation (HCT) whereas no adult patients received subsequent HCT. One patient died from complications post HCT while in remission. Therefore, the overall survival for all infused patients was 92% with a median follow-up of 9.5 months from time of infusion (range, 1-20). Conclusion: The combined pediatric and adult phase I trials of bispecific CD19/CD22 targeting CAR T cells in relapsed/refractory ALL demonstrates safety and tolerability at two dose levels. Expanded accrual at dose level 2 is ongoing and clinical outcomes will be updated. This work additionally demonstrates feasibility of delivering unified B-ALL CAR T cell therapy across age boundaries. Multi-parametric CyTOF studies permitting CAR T cell phenotyping in conjunction with single cell TCR tracking, proteomics, epigenomics and cytokine profiling are ongoing and will be used to further characterize persisting CAR T cells and define inter-product and inter-patient variability. Disclosures Muffly: Pfizer: Consultancy; KITE: Consultancy; Adaptive: Research Funding. Majzner:Xyphos Inc.: Consultancy; Lyell Immunopharma: Consultancy. Feldman:Octane Biotech, Inc.: Employment; Personalized Medicine Initiative Science: Membership on an entity's Board of Directors or advisory committees. Miklos:Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Kite-Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Juno: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Becton Dickinson: Research Funding; Miltenyi Biotech: Membership on an entity's Board of Directors or advisory committees; Precision Bioscience: Membership on an entity's Board of Directors or advisory committees; AlloGene: Membership on an entity's Board of Directors or advisory committees. Mackall:Obsidian: Research Funding; Lyell: Consultancy, Equity Ownership, Other: Founder, Research Funding; Nektar: Other: Scientific Advisory Board; PACT: Other: Scientific Advisory Board; Bryologyx: Other: Scientific Advisory Board; Vor: Other: Scientific Advisory Board; Roche: Other: Scientific Advisory Board; Adaptimmune LLC: Other: Scientific Advisory Board; Glaxo-Smith-Kline: Other: Scientific Advisory Board; Allogene: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Apricity Health: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Unum Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees.
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- 2019
34. Detectable Circulating Tumor DNA 28 Days after the CD19 CAR T-Cell Therapy, Axicabtagene Ciloleucel, Is Associated with Poor Outcomes in Patients with Diffuse Large B-Cell Lymphoma
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Erin Dean, Nasheed Hossain, Frederick L. Locke, Lik Wee Lee, Saurabh Dahiya, Katherine A. Kong, Ilan M. Kirsch, Aaron P. Rapoport, Ali Bukhari, Allison P. Jacob, Jay Y. Spiegel, David B. Miklos, Chelsea D. Mullins, Crystal L. Mackall, Gursharan K. Claire, Juliana Craig, and Matthew J. Frank
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0301 basic medicine ,medicine.medical_specialty ,business.industry ,Immunology ,Becton dickinson ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Minimal residual disease ,Clinical trial ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Circulating tumor DNA ,Family medicine ,medicine ,CAR T-cell therapy ,In patient ,Prospective cohort study ,business ,Diffuse large B-cell lymphoma ,030215 immunology - Abstract
Introduction: The autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, axicabtagene ciloleucel (Axi-cel) improved long-term survival of patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). Long-term analysis of the pivotal ZUMA-1 trial indicates a 2-year PFS of ~40% (Locke, Lancet Oncology 2018). Early identification of patients with increased relapse risk may allow for early intervention and improved outcomes. In a pilot study of 6 ZUMA-1 patients, minimal residual disease (MRD) evaluation via a next-generation sequencing MRD assay (Adaptive Biotechnologies, Seattle, WA) to assess for circulating tumor (ct)DNA, mirrored clinical outcome as assessed by PET-CT (Hossain et. al. Leukemia & Lymphoma 2019). Based on these promising results, a multi-institutional prospective study utilizing cell-free MRD assessments to predict outcomes in r/r DLBCL patients after Axi-cel therapy was initiated. Methods: To identify tumor clonotype(s), tumor DNA extracted from archival paraffin-embedded tissue underwent PCR amplification of IgH-VDJ, IgH-DJ and IgKappa/Lambda regions using universal consensus primers. CtDNA levels were measured pre-LD, 0, 7, 14, 21, 28, 56, 90, 180, 270, and 365 days following Axi-cel infusion. PET-CT scans were obtained at baseline, Day 28, Month 3, 6, and 12 with response assessed per Lugano criteria. Deauville 1-3 was considered PET-negative. The protocol prespecified that patients with less than Day 28 follow-up be excluded from analysis. Any detectable ctDNA was considered MRD positive. Results: Here we report on the pre-planned analysis of the first 50 study patients with at least a Day 28 MRD assessment and 3 months of follow up. An additional 4 patients with at least 3 months of follow-up but who did not have a Day 28 MRD assessment were also included. Baseline characteristics and clinical outcomes of patients were similar to ZUMA-1 and a real-world analysis of 295 patient who received Axi-cel (Nastoupil et al ASH 2018). The median age was 61 years old (range 19-76) (53.7% male, 46.3% female) and 59% of patients received 3 or more prior lines of therapy (range 1-6). After a median follow-up of 7.5 months, the best overall response rate was 87% (47 of 54) and complete response rate was 57% (31 of 54). The median OS was not reached and median PFS was 4.6 months (panel A). At Day 28, 56% (28 of 50) of patients were MRD negative (MRD-neg) and 44% (22 of 50) were MRD positive (MRD-pos). As compared to MRD-pos, MRD-neg correlated with improved median PFS (not reached vs. 2.96 months, p Conclusion: MRD monitoring using high-throughput sequencing of ctDNA has the potentially to make an impact on the clinical management of patients undergoing Axi-cel therapy. Furthermore, ctDNA is an informative tool to compare CAR19 therapies that vary by costimulatory domains or production methods. This technology potentially overcomes fundamental limitations of DLBCL imaging (cost, radiation exposure & limited repetition) and may minimize the need for surveillance PET-CT scans. These results provide a rationale for designing MRD-based risk-adaptive CAR T cell clinical trials. Figure Disclosures Kirsch: Adaptive Biotechnologies: Employment. Jacob:Adaptive Biotechnologies: Employment, Other: shareholder. Mullins:Adaptive Biotechnologies: Employment. Lee:Adaptive Biotechnologies: Employment, Equity Ownership. Mackall:Obsidian: Research Funding; Lyell: Consultancy, Equity Ownership, Other: Founder, Research Funding; Nektar: Other: Scientific Advisory Board; PACT: Other: Scientific Advisory Board; Bryologyx: Other: Scientific Advisory Board; Vor: Other: Scientific Advisory Board; Roche: Other: Scientific Advisory Board; Adaptimmune LLC: Other: Scientific Advisory Board; Glaxo-Smith-Kline: Other: Scientific Advisory Board; Allogene: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Apricity Health: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Unum Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Locke:Cellular BioMedicine Group Inc.: Consultancy; Kite: Other: Scientific Advisor; Novartis: Other: Scientific Advisor. Miklos:Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Juno: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Kite-Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; AlloGene: Membership on an entity's Board of Directors or advisory committees; Precision Bioscience: Membership on an entity's Board of Directors or advisory committees; Miltenyi Biotech: Membership on an entity's Board of Directors or advisory committees; Becton Dickinson: Research Funding.
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- 2019
35. Maintenance versus Induction Therapy Choice on Outcomes after Autologous Transplantation for Multiple Myeloma
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Miguel Angel Diaz, Taiga Nishihori, Amrita Krishnan, Muneer H. Abidi, Sachiko Seo, Siddhartha Ganguly, Rammurti T. Kamble, Anita D'Souza, Angelo Maiolino, David I. Marks, Kenneth R. Meehan, Adetola A. Kassim, Joe Mikhael, Hillard M. Lazarus, David H. Vesole, Jack Aiello, Cindy Lee, Asad Bashey, Cesar O. Freytes, Gorgun Akpek, Racquel Innis-Shelton, Ravi Vij, Raymond L. Comenzo, Jiaxing Huang, Robert F. Cornell, Tamila L. Kindwall-Keller, Ayman Saad, Tomer M Mark, Richard F. Olsson, Jan Cerny, Dan T. Vogl, Muthalagu Ramanathan, Robert Peter Gale, Leona Holmberg, Mehdi Hamadani, Parameswaran Hari, Shahrukh K. Hashmi, Nasheed Hossain, Mei-Jie Zhang, Jean A. Yared, Shaji Kumar, Saad Z. Usmani, Rajneesh Nath, Luciano J. Costa, Mohamed A. Kharfan-Dabaja, Robert A. Kyle, Baldeep Wirk, Yago Nieto, and Qaiser Bashir
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Oncology ,Male ,Survival ,Databases, Factual ,medicine.medical_treatment ,Myeloma ,Kaplan-Meier Estimate ,0302 clinical medicine ,Cause of Death ,Antineoplastic Combined Chemotherapy Protocols ,Relapse ,Multiple myeloma ,In Situ Hybridization, Fluorescence ,Bortezomib ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,Peripheral Nervous System Diseases ,Neoplasms, Second Primary ,Hematology ,Middle Aged ,Combined Modality Therapy ,Treatment Outcome ,030220 oncology & carcinogenesis ,Female ,Multiple Myeloma ,Proteasome Inhibitors ,medicine.drug ,Adult ,medicine.medical_specialty ,Cyclophosphamide ,Adolescent ,Maintenance ,Transplantation, Autologous ,Article ,Disease-Free Survival ,Maintenance Chemotherapy ,03 medical and health sciences ,Young Adult ,Internal medicine ,medicine ,Autologous transplantation ,Chemotherapy ,Humans ,Immunologic Factors ,Lenalidomide ,Aged ,Retrospective Studies ,Transplantation ,business.industry ,medicine.disease ,Surgery ,Regimen ,business ,030215 immunology - Abstract
Bortezomib (V), lenalidomide (R), cyclophosphamide (C), and dexamethasone (D) are components of the most commonly used modern doublet (RD, VD) or triplet (VRD, CVD) initial induction regimens before autologous hematopoietic cell transplantation (AHCT) for multiple myeloma (MM) in the United States. In this study we evaluated 693 patients receiving "upfront" AHCT after initial induction therapy with modern doublet or triplet regimens using data reported to the Center for International Blood and Marrow Transplant Research from 2008 to 2013. Analysis was limited to those receiving a single AHCT after 1 line of induction therapy within 12 months from treatment initiation for MM. In multivariate analysis, progression-free survival (PFS) and overall survival were similar irrespective of induction regimen. However, high-risk cytogenetics and nonreceipt of post-transplant maintenance/consolidation therapy were associated with higher risk of relapse. Patients receiving post-transplant therapy had significantly improved 3-year PFS versus no post-transplant therapy (55% versus 39%, P = .0001). This benefit was most evident in patients not achieving at least a complete response post-AHCT (P = .005). In patients receiving upfront AHCT, the choice of induction regimen (doublet or triplet therapies) appears to be of lower impact than use of post-transplant therapy.
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- 2016
36. Monitoring ctDNA in r/r DLBCL patients following the CAR T-cell therapy axicabtagene ciloleucel: Day 28 landmark analysis
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Ali Bukhari, Matthew J. Frank, Juliana Craig, Crystal L. Mackall, Frederick L. Locke, Ilan R. Kirsch, Erin Dean, Katherine A. Kong, Allison P. Jacob, Chelsea D. Mullins, David B. Miklos, Lik Wee Lee, Jay Y. Spiegel, Saurabh Dahiya, Gursharan K. Claire, Aaron P. Rapoport, and Nasheed Hossain
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,medicine.disease ,Lymphoma ,03 medical and health sciences ,0302 clinical medicine ,Refractory ,hemic and lymphatic diseases ,030220 oncology & carcinogenesis ,Internal medicine ,Landmark analysis ,medicine ,CAR T-cell therapy ,business ,030215 immunology - Abstract
7552 Background: Axicabtagene Ciloleucel (Axi-cel) is an autologous anti-CD19 CAR T-cell therapy approved for the treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). Long‐term analysis of the Zuma‐1 clinical trial showed ~40% of patients remained progression-free at 2 years (Locke, Lancet Oncology 2018). Early identification of patients who will later progress after CAR T cell therapy may improve clinical care and patient outcomes. Methods: As of 2/1/2019, we enrolled 50 patients on a multi-institutional, prospective study measuring circulating tumor DNA(ctDNA) minimal residual disease (MRD) in r/r DLBCL patients undergoing treatment with Axi-cel. Using an next generation sequencing-MRD assay (Adaptive Biotechnologies; Seattle WA), ctDNA levels were measured pre, 0, 7, 14, 21, 28, 56, 90, 180, 270, and 365 days following Axi-cel infusion. A pre-planned comparison between EDTA, Streck, and CFD tubes for the initial 10 enrolled patients determined the CFD tube provided optimal analyte stability over 144 hours following sample collection. CFD tubes are being used to collect all study samples. Results: 24 subjects have 3 or more months clinical follow up and their treatment ctDNA MRD significantly associated with clinical outcomes. A day 28 landmark analysis shows 12 patients were MRD negative and 12 patients were MRD positive as defined by detection of none or any tumor-associated ctDNA, respectively. 10 of 12 MRD+ patients subsequently developed progressive disease. In contrast, only 2 MRD- patients subsequently progressed and the 10 other patients remain in a CR. (p = 0.0033, Fisher's exact test). With a median follow up of 237 days, median PFS after Axi-cel infusion for day 28 MRD+ vs. MRD- patients is 93 days vs. not reach, p = 0.0010 by Log-rank test. Median OS for day 28 MRD+ vs. MRD- patients is 281 days after Axi-cel infusion vs. not reach, p = 0.0399 by Log-rank test. Conclusions: After Axi-cel infusion, day 28 ctDNA-based MRD significantly associates with PFS and OS and identified early at-risk patients prior to progression. These results provide a rationale for designing MRD-based risk-adaptive CAR T-cell clinical trials.
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- 2019
37. Predicting for Cardiac Events Following Allogeneic Hematopoietic Stem Cell Transplantation in Adults
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Patrick J. Stiff, Tony Kurian, Stephanie B. Tsai, Al Ozonoff, Patrick Hagen, Scott E. Smith, Vivian Irizarry Gatell, and Nasheed Hossain
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Transplantation ,medicine.medical_specialty ,education.field_of_study ,Framingham Risk Score ,Ejection fraction ,business.industry ,Population ,Case-control study ,Atrial fibrillation ,Hematology ,medicine.disease ,Internal medicine ,Cohort ,medicine ,Cardiology ,cardiovascular diseases ,Myocardial infarction ,business ,education ,QRISK - Abstract
Introduction Cardiovascular (CV) complications occur after hematopoietic stem cell transplantation (HCT). Risk factors for events are unclear making it difficult to determine optimal pre-transplant screening. Solid organ transplants programs calculate pre-transplant risk to determine indication for further cardiac testing. Based on this, we investigated whether several commonly used CV risk calculators predicted for CV events after HCT. Methods This was a prospective case control study at a single academic institution. CV risk was estimated using the Framingham General CVD Risk Score (2008), ACC/AHA Pooled Cohort Hard CVD Risk (ASCVD; 2013) calculator, and JBS3 QRISK Lifetime calculator. Results Forty-eight patients transplanted between 2012 and 2016 were analyzed. 27 (56%) were female. Ages ranged from 53-74 with a median of 64. Diseases transplanted were: AML (38%), MDS (31%), Non-Hodgkin's lymphoma (15%), and others 47% had high risk for CVD (score>2) by Framingham score. 67% had high risk by ASCVD calculator (10 year risk >7.5%). 70% had high risk by QRISK Lifetime calculator. 9%were low risk by Framingham score, but high risk by QRISK Lifetime calculator. Cardiac events evaluated included atherosclerotic events (myocardial infarction and stroke), atrial fibrillation (a-fib), and others (other arrhythmia, CHF, drop in LVEF, and cardiac arrest). 40% had any cardiac event. 15% had an atherosclerotic event (MI or CVA). 21% had a-fib. Framingham Risk, ASCVD and QRISK calculators did not predict for either atherosclerotic events or any cardiac events after HCT [Table 1]. Risk factors for a-fib specifically, were also evaluated: history of MI, diastolic or systolic dysfunction, CHF, valvular disease, tobacco use, diabetes, and hypertension. Only CHF was a predictor for a-fib (p=0.08). Conclusion CVD risk calculators commonly used in the general population and by solid organ transplant programs did not predict for CV events post-HCT here. However, this analysis was limited by small study size. Study in a larger population is being planned to allow incorporation of transplant related variables to develop a HCT-specific multivariate risk calculator to accurately predict post-HCT CV events.
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- 2019
38. Umbilical Cord Blood As an Alternate Donor Source for High Risk Elderly Patients Undergoing Allogeneic Stem Cell Transplantation for Hematological Malignancies
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Stephanie B. Tsai, Patrick J. Stiff, Nasheed Hossain, Scott E. Smith, Shruti Singh, William Adams, Sammi Qin, and Patrick Hagen
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Transplantation ,medicine.medical_specialty ,business.industry ,Hematology ,medicine.disease ,Umbilical cord ,Graft-versus-host disease ,medicine.anatomical_structure ,Internal medicine ,Cohort ,Medicine ,Progression-free survival ,Stem cell ,business ,Very high risk ,Cause of death - Abstract
Allogeneic stem cell transplantation (alloHCT) remains the only curative option for a variety of hematological malignancies. AlloHCT is being increasingly offered in elderly patients with acceptable transplant related mortality. Umbilical cord blood (UCB) is established as an alternate donor source however some are reluctant to consider its use in elderly patients due to anticipated morbidity. We evaluated outcomes in alternate donor sources, prior to the initiation of haploidentical transplantation at our institution, of matched unrelated donor (MUD) and UCB in elderly patients (median age 64, range 60-74) from 2005-2015. One hundred and eighty four patients were included (MRD: 57; MUD: 69; UCB: 58). Eighty seven underwent myeloablative conditioning (52.7%). There was no difference in acute (aGVHD) or chronic graft versus host disease (cGVHD) between donor sources. ATG was protective for grade III-IV aGVHD (p=0.0498) and high disease risk index per Armand et al predictive of cGVHD (p=0.0496). UCB engraftment was longer for both neutrophils (p=0.005) and platelets (p 2) comorbidity index (42%) per Sorror et al. There was a trend toward inferior progression free survival (PFS) amongst both UCB (5.50 months; 95% CI 2.83—9.36) and MUD (5.59 months; 95% CI 3.68-17.68) as compared to MRD (18.3 months; 95% CI 8.38-64.79)(Table 1). Compared to MRD, UCB experienced inferior median overall survival (OS) HR 1.877 (95% CI 1.160-3.037) but no difference was seen between UCB and MUD or MUD and MRD in multivariable analysis (Table 1 and 2). The leading cause of death in UCB recipients was infections (40%) followed by relapse (17%). Our experience shows that even in this very high risk elderly cohort, UCB continues to be a viable alternate donor source. Methods to reduce late infectious complications are needed such as new approaches to accelerate T cell engraftment which is currently being explored at our center.
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- 2019
39. Phase I Experience with a Bi-Specific CAR Targeting CD19 and CD22 in Adults with B-Cell Malignancies
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Matthew Abramian, Yasodha Natkunam, Haiying Qin, Sharon Mavroukakis, Nasheed Hossain, Stephen Kim, Jay Y. Spiegel, Matthew J. Frank, Everett Meyer, Steven R. Long, David B. Miklos, Steven A. Feldman, Lori Muffly, Crystal L. Mackall, Bita Sahaf, Terry J. Fry, Katie Kong, and Jean Oak
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,business.industry ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,03 medical and health sciences ,Cytokine release syndrome ,030104 developmental biology ,0302 clinical medicine ,Immunophenotyping ,030220 oncology & carcinogenesis ,Acute lymphocytic leukemia ,Internal medicine ,Medicine ,Chimeric Antigen Receptor T-Cell Therapy ,Cytokine secretion ,Rituximab ,business ,Diffuse large B-cell lymphoma ,Progressive disease ,medicine.drug - Abstract
Autologous CD19 directed CAR T-cell therapy has response rates of >70% in adult acute lymphoblastic leukemia (ALL) and >40% in adult diffuse large B cell lymphoma (DLBCL). Large trials (ZUMA-1/JULIET/TRANSCEND) have highlighted that many patients fail to achieve durable responses. Several groups have reported on the phenomenon of CD19 immune escape as a cause (Grupp et al, NEJM 2013, Neelapu et al, NEJM 2017) and the NIH Pediatric Oncology Branch has shown CD22 as an alternative target (Fry et al, Nat Med. 2018). We developed a bi-specific CAR construct targeting CD19 & CD22 with intracellular signaling domains incorporating 4-1BB and CD3ζ (CD19/CD22.BB.z) to overcome CD19 immune escape. Here, we present our Phase I experience with this bi-specific CAR in adults. This is a single institution phase I dose escalation study enrolling patients Age ≥ 18 years with relapsed/refractory B-ALL or DLBCL after standard therapies. Primary aim is to determine feasibility of manufacturing the bi-specific CAR and safety at three dose levels (1 x 106 CAR T cells/kg, 3 x 106 CAR T cells/kg, 1 x 107 CAR T cells/kg). Clinical response was evaluated as a secondary endpoint utilizing standard response criteria for ALL and DLBCL. All patients underwent lymphodepletion with cyclophosphamide (500mg/m2 daily x3 doses) and fludarabine (30mg/m2 daily x 3 doses) followed by CAR infusion two days later. Patients were assessed at pre-defined time-points (Day 28, Month 3, 6, 9, 12 then every 6-12 months) with correlative assessments including immunophenotyping, single cell RNAseq, CAR qtPCR, serum and single cell cytokine analysis. Seven adult patients (5 DLBCL, 2 ALL), aged 35 - 75 years have been enrolled and 6 treated, all at dose Level 1 [Table 1]. The first 3 patients received freshly harvested cells and the remaining received cryopreserved cells (1 patient treated twice received initial fresh then cryopreserved product). None received systemic bridging therapy before CAR T infusion. Six patients developed reversible cytokine release syndrome (CRS,4 with Grade 1, 2 with Grade 2), onset between Day 1 to 13, and 2 patients received tocilizumab & systemic steroids. Three patients developed neurotoxicity (1 with grade 2, Day 8-11 and the others grade 1) with grade 2 neurotoxicity managed with steroids. Four patients required growth factor support beyond Day 28 and all treated patients show persistent B-cell aplasia. Two patients achieved CR: an ALL patient with disease in bone marrow/blood/CNS was MRD negative at day 28 & 60; a 75yo DLBCL patient achieved PR at day 28 and CR at month 3. Three others have ongoing PR and one died of progressive disease after initial PR at Day 28. A patient with PD at Day 28 subsequently treated with radiation and 2-months of revlimid/rituximab, now has no detectable disease 6 months post CAR-T. One patient with initial 6-month PR received a second infusion due to PD, did not develop CRS or CRES with 2nd infusion and has SD at Day 28 Notably, the patient experienced a lack of CAR-T expansion with the second infusion, raising the possibility of an immunogenic response to the CAR-T cell infusion. Flow analysis of all patients' peripheral blood showed CAR expansion peaked at median Day 13 (range Day 10-20) and CARs remained detectable [Figure 1]. Multi-parametric CyTOF phenotyping of the CAR19-22 products showed significant numbers of transduced CAR-T memory stem cells (phenotype: CD3+CD8+CD45RA+CD127+CD27+CCR7+). Single cell cytokine secretion analysis (Isoplexis,Rossi et al Blood 2018) revealed high polyfunctional strength index (PSI) in both CD4+ and CD8+ cell subsets in each patient's pre-infusion CAR product that reflected phenotypic expansion in patients. Additional correlative studies, including cytokine analysis, qtPCR based CAR quantification and CyTOF phenotypic analysis of the CAR-T cells will be presented. This first adult phase I trial of bi-specific CAR targeting CD19 & CD22 shows low toxicity with promising efficacy including achievement of CR in adult DLBCL and ALL patients. We have escalated dose to 3x 106 CAR T cells/kg and an expansion study of 60 patients will follow. CAR-T cells expanded within the first 20 days and continue to be detectable through 6 months. Disclosures Muffly: Shire Pharmaceuticals: Research Funding; Adaptive Biotechnologies: Research Funding. Miklos:Janssen: Consultancy, Research Funding; Genentech: Research Funding; Pharmacyclics - Abbot: Consultancy, Research Funding; Kite - Gilead: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy, Research Funding; Novartis: Consultancy, Research Funding.
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- 2018
40. Elevated Axicabtagene Ciloleucel (CAR-19) Expansion By Immunophenotyping Is Associated with Toxicity in Diffuse Large B-Cell Lymphoma
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Matthew Abramian, David B. Miklos, Wen-Kai Weng, Jay Y. Spiegel, Bita Sahaf, Juancarlos Cancilla, Steven R. Long, Laura Johnston, Crystal L. Mackall, Jean Oak, Matthew J. Frank, Sally Arai, Yasodha Natkunam, Everett Meyer, Andrew R. Rezvani, Theresa Latchford, Nasheed Hossain, Gursharan K. Claire, Judith A. Shizuru, Robert S. Negrin, Robert Lowsky, Lori Muffly, Katherine A. Kong, and Bertha Villa
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medicine.medical_specialty ,Chemotherapy ,Pleural effusion ,business.industry ,medicine.medical_treatment ,Immunology ,Aggressive lymphoma ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Chemotherapy regimen ,Gastroenterology ,Lymphoma ,03 medical and health sciences ,0302 clinical medicine ,Immunophenotyping ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,business ,Diffuse large B-cell lymphoma ,Dexamethasone ,030215 immunology ,medicine.drug - Abstract
Background: Axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR-T), showed significant clinical responses in patients with relapsed-refractory large-B cell lymphomas in the Zuma-1 trial (Neelapu et al, NEJM 2017). Zuma-1 analysis showed blood CAR-T cell expansion was associated with clinical response and toxicity. Herein, we report on 25 patients treated with commercial axi-cel and describe CAR-T expansion by immunophenotyping and its correlation with clinical outcomes. Methods: Twenty-five patients with aggressive lymphoma consecutively apheresed at Stanford University prior to June 30, 2018 were studied on an IRB approved biorepository-clinical outcome protocol. Cytokine release syndrome (CRS) was graded by Lee criteria (Blood 2014) and neurotoxicity according to Neelapu et. al (Nat. Rev. Clin. Onc. 2017). CAR-T cell immunophenotyping was assessed by peripheral blood flow cytometry on days 7, 14, 21 and 28 and then monthly. CAR-T cells were identified by gating on singlet+, live+, CD45+, CD14-, CD3+, anti-CD19-specific CAR mAb (clone 136.20.1; Jena et. al Plos 2013) and characterized as either CD4+ or CD8+. Results: Of 25 apheresed patients, 3 patients died prior to axi-cel infusion due to progressive lymphoma. Of 22 infused patients, 14 (64%) would have been eligible for the Zuma-1 trial. Reasons for ineligibility included symptomatic DVT (n=2), renal insufficiency (n=1), transaminitis (n=1), thrombocytopenia (n=1), MDS (n=1), pleural effusion (n=1) and 1 was ineligible by multiple criteria. Median time from initial clinic visit to infusion was 47 days (range 34-117); median time from apheresis to infusion was 22 days (range 19-38). Nine patients received bridging therapy prior to lymphodepletion chemotherapy (chemo = 4, radiation = 2, high dose dexamethasone = 3). Axi-cel infusion occurred in hospital and patients were followed expectantly for a minimum of 7 days or until adverse events resolved to Ninety-five percent of patients developed CRS (Grade 2 = 73%, none ≥Grade 3). Median number of tocilizumab doses was 1 (range 0-4). Neurotoxicity occurred in 64%, Grade 3 or 4 in 27%. Corticosteroid therapy was required in 82% (77% received both tocilizumab and steroids). Median duration of steroids was 8.5 days (range 1-30); 12 patients required at least 1 week and 4 patients ≥2 weeks. Of patients infused, complete response (CR) at day 28 was 45% (ORR 86%). Of 15 patients evaluable at 3 months, ORR was 53% (CR = 7, PR = 1) and 47% progressed, similar to Zuma-1. Ineligibility for Zuma-1 was not associated with inferior outcomes. Overall, median day 7 peak in vivo axi-cel expansion using anti-CAR19 flow cytometry was 38 CAR-T/ul (Fig. 1A), matching RT-PCR measured levels reported in Zuma-1. As shown in Fig. 1A, the majority of CAR-T cells were CD8+. Patients with Grade 2 CRS had significantly higher peak expansion of CAR-T cells (both CD4+ and CD8+) as compared to those with either Grade 0 or 1 CRS (Fig. 1B). Grades 2-4 neurotoxicity were significantly associated with peak total and CD8+ CAR-T but not CD4+ (Fig. 1B). Illustratively, 2 patients with the most robust CAR-T expansion (▪, ▼ Fig. 1A) experienced Grade 4 neurotoxicity including status epilepticus requiring multiple anti-epileptics and intubation. Peak CAR-T expansion in blood did not correlate with CR or ORR at day 28; expansion did not differ between patients who did or did not require steroids. Fine needle aspirates (FNA) on a subset of patients with FDG-avid lymph nodes 2-3 days post axi-cel showed significant CAR-T expansion within the node despite low detectable circulating CAR-T. Figure 1C depicts a 76-year-old male with double expressor DLBCL who attained a CR at day 28; day 14 blood CAR-T expansion was below average (6 CAR-T/ul), while his day 2 FNA showed >35% of CD3+ T-cells expressed CAR19. As of submission, 34 patients were apheresed and updated blood and FNA results will be presented. Conclusion: Our analysis of 22 infused axi-cel patients showed an ORR of 86% and CR of 45%, despite 36% Zuma-1 ineligibilities and steroid use in 82%. Blood CAR-T expansion was associated with both CRS and neurotoxicity but not clinical response. Detection of high concentration of CAR-T cells in affected lymph nodes 2 days post infusion suggests quantification of CAR-T cells at disease sites could be predictive of clinical responses. J.Y.S and B.S are co-first authors Disclosures Latchford: Kite a Gilead Company: Speakers Bureau. Muffly:Adaptive Biotechnologies: Research Funding; Shire Pharmaceuticals: Research Funding. Miklos:Kite - Gilead: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Genentech: Research Funding; Novartis: Consultancy, Research Funding; Pharmacyclics - Abbot: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy, Research Funding.
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- 2018
41. Target Antigen Downregulation and Other Mechanisms of Failure after Axicabtagene Ciloleucel (CAR19) Therapy
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Bita Sahaf, David B. Miklos, Jean Oak, Jay Y. Spiegel, Katherine A. Kong, Steven R. Long, Crystal L. Mackall, Nasheed Hossain, and Yasodha Natkunam
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0301 basic medicine ,medicine.medical_specialty ,biology ,Disease Response ,business.industry ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,BCL6 ,Biochemistry ,Gastroenterology ,CD19 ,Lymphoma ,03 medical and health sciences ,030104 developmental biology ,medicine.anatomical_structure ,Internal medicine ,medicine ,biology.protein ,business ,B-cell lymphoma ,Diffuse large B-cell lymphoma ,B cell ,Progressive disease - Abstract
Introduction: Autologous anti-CD19 chimeric antigen receptor T cells (CAR19) have shown dramatic clinical responses in relapsed-refractory large B cell lymphomas, but more than 50% of patients will have disease progression. Here we characterize the observed mechanisms of treatment failure following Axicabtagene Ciloleucel (Axi-cel) therapy. Methods: Sixty-nine patients with refractory large B cell lymphoma were referred for CAR19 therapy from October 2017 to June 2018. The WHO diagnosis and B cell antigen expression on lymphoma cells were assessed by immunohistochemistry and/or flow cytometry before and at the time of progression. We assessed peripheral blood CAR-T cell numbers at Days 7, 14, 21, and 28 by flow cytometry immunophenotyping and monitored disease response with PET-CT at Day 28, 3 months, and 6 months post-infusion. Results: Twenty-two patients who received CAR19 therapy, including patients with transformed large B cell lymphoma (N =5), diffuse large B cell lymphoma, not otherwise specified (N =11), high grade B cell lymphoma, not otherwise specified (N = 2), primary mediastinal large B cell lymphoma (N = 2), and high grade B cell lymphoma with rearrangement of MYC and BCL2 or BCL6 (N =2). The Day 28 ORR was 86%: 10 patients had complete response, 9 had a partial response, 1 had stable disease, and 2 had progressive disease. There was no statistically significant difference in age, gender, underlying disease, or number of prior treatment regimens between patients who achieved a clinical response versus those who failed therapy. Both patients (2 of 2) with progressive disease at Day 28 showed dim or partial CD19 expression prior to CAR-T infusion but nonetheless demonstrated robust Axi-cel expansion. In contrast, one patient with Day 28 stable disease showed no CAR-T cell expansion despite intact CD19 expression. Overall, there was no statistical difference in relative or absolute CAR+ T cells in patients who responded versus those who did not at Day 28 (Figure 1). Day 90 response was available for 12 patients with either CR or PR at Day 28. Five patients (26%) developed progressive disease, and 4 of 5 underwent repeat biopsy. Of these patients, 2 had complete loss of tumor CD19 (Figure 2) and another had downregulation of CD19 with variable expression of other B cell antigens. Conclusion: Eight of 22 (36%) of patients who underwent CAR19 infusion did not respond or relapsed after Day 28 response. Five patients (62%) who failed therapy had loss or downregulation of CD19, which emphasizes that single target antigen loss is a common mechanism of CAR-T failure. However, lack of CAR-T cell expansion was noted in multiple patients, suggesting that there may be T cell intrinsic causes of treatment failure. Further studies are necessary to help identify and predict which patients will benefit from targeted immunotherapy. Disclosures No relevant conflicts of interest to declare.
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- 2018
42. T-Cell Receptor-Engineered Cells for the Treatment of Hematologic Malignancies
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Nasheed Hossain, Roland B. Walter, and Aude G. Chapuis
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0301 basic medicine ,Cancer Research ,Adoptive cell transfer ,Myeloid ,medicine.medical_treatment ,Cell- and Tissue-Based Therapy ,Receptors, Antigen, T-Cell ,Human leukocyte antigen ,Immunotherapy, Adoptive ,03 medical and health sciences ,Immune system ,Antigens, Neoplasm ,HLA-A2 Antigen ,Medicine ,Humans ,Cell Engineering ,business.industry ,T-cell receptor ,Membrane Proteins ,Hematology ,Immunotherapy ,Chimeric antigen receptor ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Hematologic Neoplasms ,Immunology ,Cancer cell ,business - Abstract
Recent attention in adoptive immunotherapy for hematologic malignancies has focused on lymphocytes expressing chimeric antigen receptors. An alternative technique to redirect the immune system toward cancer cells involves the use of T-cells carrying an engineered tumor-recognizing T-cell receptor (TCR). This approach allows targeting of surface or intracellular/nuclear proteins as long as they are processed and presented on the cell surface by human leukocyte antigen molecules. Several trials in advanced solid tumors, particularly melanoma and synovial sarcoma, support the validity of this strategy, although tumor responses have often been short-lived. Emerging data from patients with multiple myeloma and myeloid neoplasms suggest that the benefit of TCR-modified cells may extend to blood cancers. Methodological refinements may be necessary to increase the in vivo persistence and functionality of these cells. Particularly with affinity-enhanced TCRs, however, more effective therapies may increase the potential for serious toxicity due to the unexpected on- or off-target reactivity.
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- 2016
43. The Management of Thyroid and Parathyroid Cancer
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Colleen Veloski, Nasheed Hossain, and Ranee Mehra
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endocrine system ,medicine.medical_specialty ,endocrine system diseases ,business.industry ,Thyroid ,Cancer ,Medullary thyroid cancer ,medicine.disease ,Vascular endothelial growth factor ,Pathogenesis ,chemistry.chemical_compound ,Endocrinology ,medicine.anatomical_structure ,Parathyroid carcinoma ,chemistry ,Internal medicine ,medicine ,Cancer research ,Endocrine system ,business ,Thyroid cancer - Abstract
Thyroid and parathyroid cancers are both relatively uncommon malignancies; however, the yearly incidence of thyroid cancer has nearly tripled since 1975. The mainstay of treatment of these endocrine malignancies has been surgical resection and radioactive iodine treatment for thyroid cancer. Differentiated thyroid cancers encompass papillary and follicular carcinomas and are responsive to radioactive iodine treatment and TSH suppression, in contrast to medullary thyroid cancer. There is now a greater understanding of the molecular pathogenesis of differentiated thyroid cancers, poorly differentiated and anaplastic thyroid cancers, and medullary thyroid cancer. This has prompted numerous phase studies utilizing oral biologically targeted agents that inhibit a variety of tyrosine kinase inhibitors, such as the vascular endothelial growth factor receptors, c-Kit, RET, and PDGFR. This review will discuss the epidemiology, histologies, pathogenesis, and issues in management of thyroid and parathyroid cancers.
- Published
- 2016
44. CMV and BK Virus Reactivation in Post Transplant Cyclophosphamide (PTCY) after Allogeneic MUD, MRD and Haploidentical Transplant
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Carlyn Rose C. Tan, Patricia Kropf, Trent P Wang, Stefan K. Barta, John Ulicny, Matthew Sochat, Henry C. Fung, Nasheed Hossain, and Philip A. Pancari
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0301 basic medicine ,Transplantation ,business.industry ,Post transplant cyclophosphamide ,Hematology ,medicine.disease_cause ,Virology ,BK virus ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,medicine ,business - Published
- 2017
45. Donor Lymphocyte Infusion in Hematologic Malignancies--Good to be Fresh?
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Michael Garner, Thomas R. Klumpp, Nasheed Hossain, Mangan Kf, Mary Ellen Martin, John Ulicny, Stefan K. Barta, Henry C. Fung, and Patricia Kropf
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Cancer Research ,medicine.medical_specialty ,Lymphocyte Transfusion ,medicine.medical_treatment ,Subgroup analysis ,Hematopoietic stem cell transplantation ,Gastroenterology ,Donor lymphocyte infusion ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Retrospective Studies ,business.industry ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Retrospective cohort study ,Hematology ,Chemotherapy regimen ,Tissue Donors ,Surgery ,Transplantation ,Oncology ,030220 oncology & carcinogenesis ,Hematologic Neoplasms ,Neoplasm Recurrence, Local ,business ,030215 immunology ,Follow-Up Studies - Abstract
Background Donor lymphocyte infusion (DLI) has been used with variable success in a variety of hematologic malignancies. Patients and Methods We conducted a retrospective analysis of all patients who were treated with DLI for persistent or relapsed disease at the Temple University Bone Marrow Transplant Unit from July 1, 1993 to December 31, 2013 to evaluate the effect of the type of DLI (fresh vs. cryopreserved) on event-free survival (EFS) and overall survival (OS). Median follow-up was 64.8 months (range, 0.3-142.6 months). Results We found that EFS and OS were similar between patients receiving cryopreserved cells and those receiving fresh DLI (median OS for cryopreserved cells, 0.39 years; median OS for fresh cells, 0.32 years; P = .793; median EFS for cryopreserved cells, 0.410 years; median EFS for fresh cells, 0.420 years; P = .4264). In the setting of relapsed disease, treatment with any chemotherapy regimen before receiving DLI did not significantly impact OS (n = 63; P = .2203) or EFS (n = 40; P = .542). A subgroup analysis limited to patients with acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) (32 patients) showed that differences in OS and EFS between cryopreserved and fresh DLI approached significance (median OS for cryopreserved cells, 0.34 years; median OS for fresh cells, 0.17 years; P = .16; median EFS for cryopreserved cells, 0.37 years; median EFS for fresh cells, 0.094 years; P = 0.11). Conclusion We conclude that the use of fresh cells versus cryopreserved cells does not have an impact on outcomes, and selected patients can achieve long-term survival with DLI for treatment of relapse after transplantation, although the overall outcomes remain dismal.
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- 2015
46. Progressive Disease after Autologous Stem Cell Transplant (ASCT) for Patients with DLBCL in the Rituximab Era: Outcome Analysis and Evaluation of Prognostic Factors
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Henry C. Fung, Mary Ellen Martin, John Ulicny, Nasheed Hossain, Patricia Kropf, and Stefan K. Barta
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Oncology ,medicine.medical_specialty ,Transplantation ,business.industry ,Outcome analysis ,Hematology ,medicine.disease ,Internal medicine ,Immunology ,medicine ,Rituximab ,Stem cell ,business ,Progressive disease ,medicine.drug - Published
- 2016
- Full Text
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47. GVHD Prophylaxis with Post-Transplant High Dose Cyclophosphamide: Impact on Engraftment, Treatment-Related Mortality and Resource Utilization
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Mary Ellen Martin, Patricia Kropf, Henry C. Fung, Stefan K. Barta, Nasheed Hossain, and John Ulicny
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medicine.medical_specialty ,Transplantation ,business.industry ,Hematology ,Post transplant ,Treatment related mortality ,surgical procedures, operative ,High dose cyclophosphamide ,immune system diseases ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Gvhd prophylaxis ,business ,Resource utilization - Published
- 2016
- Full Text
- View/download PDF
48. Diffuse Large B-Cell Lymphoma with Primary Treatment Failure: Identification of Ultra-High Risk Patients and Benchmarking for Experimental Therapies
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Saurabh Chhabra, Reem Karmali, Deniz Peker, Timothy S. Fenske, Zeina Al-Mansour, Julio C. Chavez, Oscar Calzada, Cristiana A Costa, Luciano J. Costa, Veronika Bachanova, Andrew G. Evans, Francisco J. Hernandez-Ilizaliturri, Frederick Lansigan, Kami J. Maddocks, Jonathon B. Cohen, Christopher R. Flowers, Elvira Umyarova, Amitkumar Mehta, Nasheed Hossain, Mehdi Hamadani, Andre Forero-Torres, Zheng Zhou, Ana C. Xavier, Martha Glenn, Stefan K. Barta, Nishitha Reddy, Michael Jaglal, and Narendranath Epperla
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medicine.medical_specialty ,education.field_of_study ,business.industry ,Immunology ,Population ,Salvage therapy ,Cell Biology ,Hematology ,Benchmarking ,Ultra high risk ,medicine.disease ,Biochemistry ,Transplantation ,Clinical trial ,Family medicine ,medicine ,Primary treatment ,education ,business ,Diffuse large B-cell lymphoma - Abstract
Introduction: Most patients (pts) with diffuse large B cell lymphomas (DLBCL) are cured with first line chemoimmunotherapy including an anthracycline and rituximab. Pts who obtain complete remission (CR) but latter relapse often can be cured with salvage therapy and autologous hematopoietic cell transplantation (auto-HCT). This management paradigm often is applied to pts with primary treatment failure (PTF). However, this group is heterogeneous and detailed data on outcomes in current era is needed to identify the DLBCL pts for whom novel therapeutic strategies should be designed. Methods: Fifteen US academic medical centers contributed pts to the REgistry of diFfuse large B cell lymphoma with prImary treatmeNt failurE (REFINE) collaboration. REFINE retrospectively captured patient, disease and treatment characteristics and treatment response as assessed by treating physician. Eligible pts were ≥ 18 years diagnosed with DLBCL during 2008-2015, who received upfront cheomoimmunotherapy including anthracycline and CD20-directed antibody and developed one of 3 patterns of PTF: relapse < 6 months following CR (early relapse- ER); only partial remission (PR) or stable disease (SD) with upfront therapy (residual disease-RD); progressive disease (PD) while receiving upfront therapy (primary progression-PP). Pts with HIV infection, primary CNS lymphoma or lymphoma transforming from a more indolent histology were excluded. Results: Patient characteristics for the 331 cases are summarized in Table 1. Median follow up of survivors was 18.9 months. R-CHOP was the upfront treatment for 87.6% of pts. Nearly all pts (94.6%) received salvage therapy after PTF and prior to any HCT, with a median of 1 and range 0 to 5 regimens. Response to first salvage regimen was CR in 19.9%, PR in 21.8%, SD in 9.0% and PD in 40.8%. Only 15.1% of pts were enrolled in clinical trials. One hundred and thirty-two pts (39.9%) underwent auto-HCT and 33 (10.0%) allogeneic-HCT (8 after failure of auto-HCT). Two-year overall survival (OS) from time of PTF was 45.5% (95% C.I. 34.5-56.5%) for ER, 30.6% (95% C.I. 20.0-41.2%) for RD and 18.5% (95% C.I. 11.4-25.6%) for PP (P Conclusions: Pts with DLBCL experiencing PTF have poor prognosis but low clinical trial participation even when treated in academic centers. Pts with PP disease, intermediate-high/high NCCN-IPI at time of PTF or with c-myc(+) tumors constitute a UHR category with dismal outcomes on existing therapies. REFINE provides benchmarking for future experimental agents targeting this population. UHR pts represent an unmet medical need and should receive high priority for development of new drugs and cellular therapies. Table 1. Table 1. Figure 1. Figure 1. Disclosures Chavez: Janssen: Speakers Bureau. Reddy:INFINITY: Membership on an entity's Board of Directors or advisory committees; celgene: Membership on an entity's Board of Directors or advisory committees; KITE: Membership on an entity's Board of Directors or advisory committees; GILEAD: Membership on an entity's Board of Directors or advisory committees. Karmali:Celgene: Speakers Bureau. Calzada:Seattle Genetics: Research Funding. Barta:Janssen: Honoraria, Speakers Bureau; Celgene, Merck, Seattle Genetics: Research Funding. Lansigan:Spectrum: Consultancy, Research Funding; Pharmacyclics: Consultancy; Celgene: Consultancy; Teva: Research Funding. Flowers:Roche: Consultancy, Research Funding; Acerta: Research Funding; TG Therapeutics: Research Funding; NIH: Research Funding; Pharmacyclics, LLC, an AbbVie Company: Research Funding; Infinity: Research Funding; Gilead: Consultancy, Research Funding; Millenium/Takeda: Research Funding; ECOG: Research Funding; AbbVie: Research Funding; Mayo Clinic: Research Funding; Genentech: Consultancy, Research Funding. Fenske:Seatle Genetics: Honoraria; Millennium/Takeda: Research Funding; Celgene: Honoraria; Pharmacyclics: Honoraria. Cohen:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium/Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Hamadani:Takeda: Research Funding. Costa:Sanofi: Honoraria, Research Funding.
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- 2016
49. Primary Failure Diffuse Large B Cell Lymphoma: Early Autologous or Donor Hematopoietic Cell Transplantation Not Effective in Patients with Ultra-High Risk Features
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Cristiana A Costa, Timothy S. Fenske, Zeina Al-Mansour, Saurabh Chhabra, Luciano J. Costa, Reem Karmali, Michael Jaglal, Narendranath Epperla, Jonathon B. Cohen, Mehdi Hamadani, Kami J. Maddocks, Francisco J. Hernandez-Ilizaliturri, Frederick Lansigan, Nishitha Reddy, Zheng Zhou, Julio C. Chavez, Andrew G. Evans, Veronika Bachanova, Elvira Umyarova, Nasheed Hossain, Oscar Calzada, Ana C. Xavier, Martha Glenn, Stefan K. Barta, and Christopher R. Flowers
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medicine.medical_specialty ,education.field_of_study ,Hematopoietic cell ,business.industry ,Immunology ,Population ,Salvage therapy ,Cell Biology ,Hematology ,Ultra high risk ,medicine.disease ,Biochemistry ,Treatment characteristics ,Transplantation ,Family medicine ,medicine ,In patient ,education ,business ,Diffuse large B-cell lymphoma - Abstract
Introduction: Modern chemoimmunotherapy cures the majority of patients (pts) with newly diagnosed diffuse large B cell lymphomas (DLBCL). The paradigm for pts who relapse has been salvage chemotherapy followed by autologous hematopoietic cell transplantation (auto-HCT) when chemosensitive disease. This approach is often also applied to pts with primary treatment failure (PTF), although this group is heterogeneous and outcomes of HCT in this population have not been well described. Methods: Fifteen US academic medical centers contributed pts to the REgistry of diFfuse large B cell lymphoma with prImary treatmeNt failurE (REFINE) collaboration. REFINE retrospectively captured patient, disease and treatment characteristics and response as assessed by treating center. Eligible pts were ≥ 18 years diagnosed with DLBCL during 2008-2015, who received upfront therapy including anthracycline and CD20-directed antibody and developed one of 3 patterns of PTF: relapse < 6 months following CR (early relapse- ER); only partial remission (PR) or stable disease (SD) with upfront therapy (residual disease-RD); progressive disease (PD) while receiving upfront therapy (primary progression-PP). Pts with HIV infection, primary CNS lymphoma or lymphoma transforming from a more indolent histology were excluded. Results: Among 331 cases included in REFINE, patterns of PTF were ER in 95 (28.7%), RD in 92 (27.8%) and PP in 144 (43.5%) pts. Salvage therapy was administered to 94.6% of pts. We analyzed the 157 (47.4%) PTF pts who subsequently underwent HCT, 132 auto-HCT and 33 allo-HCT (8 after failure of auto-HCT) (Table). Nearly half of pts were in CR at transplant, after 1-2 lines of salvage therapy. Among all pts receiving auto-HCT, 2-year progression-free survival (PFS) from time of transplant was 38.4% (95% C.I. 29.6-47.2%) and overall survival (OS) 54.9% (95% C.I. 44.9-64.9%). Two-year OS from auto-HCT was affected by pattern of PTF: 71.3% for ER, 55.0% for RD and 41.7% for PP (P=0.05). OS at 2-years was 23.7% for auto-HCT pts with germinal center B (GCB)type,c-myc(+) (by FISH) tumors vs. 66.7% for GCB, c-myc (-), vs. 67.8% for non-germinal center (NGC) (P=0.01). Auto-HCT pts with intermediate-high/high NCCN-IPI at time of PTF had 2-year OS of 28.6% vs. 66.0% for intermediate-low and 80.9% for low risk (P Conclusions: Pts with DLBCL experiencing PTF and 2 or more UHF features have dismal outcome after auto-HCT and should be targeted for experimental modalities of cellular therapy. Outcomes of allo-HCT in DLBCL with PTF are poor, due to rapid and fatal relapses. Table. Table. Figure. Figure. Disclosures Costa: Sanofi: Honoraria, Research Funding. Reddy:INFINITY: Membership on an entity's Board of Directors or advisory committees; KITE: Membership on an entity's Board of Directors or advisory committees; celgene: Membership on an entity's Board of Directors or advisory committees; GILEAD: Membership on an entity's Board of Directors or advisory committees. Karmali:Celgene: Speakers Bureau. Chavez:Janssen: Speakers Bureau. Calzada:Seattle Genetics: Research Funding. Barta:Janssen: Honoraria, Speakers Bureau; Celgene, Merck, Seattle Genetics: Research Funding. Flowers:Pharmacyclics, LLC, an AbbVie Company: Research Funding; Mayo Clinic: Research Funding; Acerta: Research Funding; Roche: Consultancy, Research Funding; TG Therapeutics: Research Funding; ECOG: Research Funding; Genentech: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; NIH: Research Funding; Infinity: Research Funding; Millenium/Takeda: Research Funding; AbbVie: Research Funding. Fenske:Seatle Genetics: Honoraria; Pharmacyclics: Honoraria; Celgene: Honoraria; Millennium/Takeda: Research Funding. Cohen:Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium/Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding. Hamadani:Takeda: Research Funding.
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- 2016
50. Clinicopathologic Features and Survival Outcomes of Secondary Mantle Cell Lymphoma after Primary Solid Malignancy
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Nasheed Hossain, Muhammad Saad Hamid, Patricia Kropf, Raji Shameem, and Jeffrey Mufson
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medicine.medical_specialty ,Proportional hazards model ,business.industry ,Endometrial cancer ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Malignancy ,Biochemistry ,Gastroenterology ,Cancer registry ,Internal medicine ,medicine ,Surveillance, Epidemiology, and End Results ,Pacific islanders ,Mantle cell lymphoma ,Stage (cooking) ,business - Abstract
Background: Mantle Cell Lymphoma (MCL) is a rare sub-type of Non-Hodgkin's Lymphoma (NHL). Outcomes of secondary MCL (sMCL) in patients with a prior diagnosis of a solid malignancy as compared to de novo MCL are not well understood. Differences may be attributable to age, gender, race/ethnicity, extra-nodal involvement, and stage at initial diagnosis. We sought to determine differences in outcome by analyzing data from a large nationwide cancer registry. Methods: The Surveillance Epidemiology and End Results (SEER) database (1973-2012) was used to detect MCL (ICD-O-3 code: 9673/3) adult (>18 years) cases. The variable "First Malignant Primary Indicator" was used to differentiate between de novo and sMCL cases. Primary solid malignancy subtypes categorized included prostate, breast, colorectal, lung bladder, renal, head and neck, thyroid, testicular, and endometrial cancer. Selected sMCL cases included patients with a diagnosis of a primary solid malignancy with a latency period ≥ 2 months. Overall survival (OS) was calculated using the cox regression model to determine the impact of sMCL on survival, adjusting for age at diagnosis, race/ethnicity, primary solid malignancy subtype type and latency period. Chi square test was utilized to ascertain for any significant difference between de novo MCL and sMCL cases. Results: Overall, 8,889 patients were included: 875 (9.8%) sMCL and 8,014 (90.2%) de novo MCL cases. For de novo MCL, 67.1% were males. Race/ethnicity in descending frequency consisted of Non-Hispanic Whites (NHW) (81.8%), Hispanics (8.4%), Blacks (4.4%), Asian and Pacific Islanders(API)(4.1%) and American Indian/Native Indian (AI) (0.4%). The most frequent stage at initial diagnosis for de novo MCL was stage IV (57.9%) followed by stage III (13.4%), stage II (8.1%) and stage I (10.0%). Males consisted of 75.4% of sMCL cases. Cases of sMCL categorized by race/ethnicity in descending frequency were NHW (87.3%), Hispanics (5.1%), Blacks (4.2%), API (3.2%) and AI (0.1%). Stage at diagnosis for sMCL was most frequently stage IV (54.6%), followed by stage III (15.8%), stage II (10.9%) and stage I (11.7%). Compared to de novo MCL, sMCL cases were more likely to occur in patient's ≥75 years (48.3% vs. 28.7%, p Conclusion: Our analysis demonstrates that elderly age appears to be significantly more common in sMCL cases as compared to de novo MCL. By contrast, race/ethnicity, and extra-nodal involvement were similar between the two groups. Survival was worse in sMCL compared to de novo MCL. This may be due to differences in treatment preferences. Further studies are necessary to elucidate the etiology for such differences in outcomes. Disclosures Kropf: Teva Pharmaceuticals: Consultancy.
- Published
- 2015
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