248 results on '"Melhem Solh"'
Search Results
2. Loncastuximab tesirine in relapsed/refractory diffuse large B-cell lymphoma: long-term efficacy and safety from the phase II LOTIS-2 study
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Paolo F. Caimi, Weiyun Z. Ai, Juan Pablo Alderuccio, Kirit M. Ardeshna, Mehdi Hamadani, Brian Hess, Brad S. Kahl, John Radford, Melhem Solh, Anastasios Stathis, Pier Luigi Zinzani, Ying Wang, Yajuan Qin, Luqiang Wang, Zhiying Cindy Xu, and Carmelo Carlo-Stella
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Therapies that demonstrate durable, long-term responses with manageable safety and tolerability are needed for patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Loncastuximab tesirine (loncastuximab tesirine-lpyl [Lonca]), an anti-CD19 antibody conjugated to a potent pyrrolobenzodiazepine dimer, demonstrated single-agent antitumor activity in the pivotal phase II LOTIS-2 study in heavily pretreated patients with R/R DLBCL. Here we present updated efficacy and safety analyses from LOTIS-2, performed for all patients and in subsets of patients with a complete response (CR), including patients with CR who were event-free (no progressive disease or death) for ≥1 year and ≥2 years from cycle 1, day 1 of treatment. Lonca was administered every 3 weeks (0.15 mg/kg for 2 cycles; 0.075 mg/kg for subsequent cycles). As of the final data cutoff (September 15, 2022; median follow-up: 7.8 months [range, 0.3-42.6]), 70 of 145 (48.3%) patients achieved an overall response. Thirty-six (24.8%) patients achieved CR, of which 16 (44%) and 11 (31%) were event-free for ≥1 year and ≥2 years, respectively. In the all-treated population, the median overall survival was 9.5 months; the median progression-free survival was 4.9 months. Among patients with CR, median overall survival and progression-free survival were not reached, with 24-month overall and progression-free survival rates of 68.2% (95% CI: 50.0-81.0) and 72.5% (95% CI: 48.2-86.8), respectively. No new safety concerns were detected. With additional follow-up, Lonca continued to demonstrate durable, long-term responses with manageable safety and tolerability in patients with CR (clinicaltrials gov. Identifier: NCT03589469).
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- 2023
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3. P1132: LONG-TERM RESPONSES WITH LONCASTUXIMAB TESIRINE: UPDATED RESULTS FROM LOTIS-2, THE PIVOTAL PHASE 2 STUDY IN PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA
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Paolo F Caimi, Weiyun Z Ai, Juan Pablo Alderuccio, Kirit M Ardeshna, Mehdi Hamadani, Brian Hess, Brad S Kahl, John Radford, Melhem Solh, Anastasios Stathis, Pier Luigi Zinzani, Ying Wang, Yajuan Qin, Luqiang Wang, Cindy Xu, and Carmelo Carlo-Stella
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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4. Association between the choice of the conditioning regimen and outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis
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Guru Subramanian Guru Murthy, Soyoung Kim, Noel Estrada-Merly, Muhammad Bilal Abid, Mahmoud Aljurf, Amer Assal, Talha Badar, Sherif M. Badawy, Karen Ballen, Amer Beitinjaneh, Jan Cerny, Saurabh Chhabra, Zachariah DeFilipp, Bhagirathbhai Dholaria, Miguel Angel Diaz Perez, Shatha Farhan, Cesar O. Freytes, Robert Peter Gale, Siddhartha Ganguly, Vikas Gupta, Michael R. Grunwald, Nada Hamad, Gerhard C. Hildebrandt, Yoshihiro Inamoto, Tania Jain, Omer Jamy, Mark Juckett, Matt Kalaycio, Maxwell M. Krem, Hillard M. Lazarus, Mark Litzow, Reinhold Munker, Hemant S. Murthy, Sunita Nathan, Taiga Nishihori, Guillermo Ortí, Sagar S. Patel, Marjolein van der Poel, David A. Rizzieri, Bipin N. Savani, Sachiko Seo, Melhem Solh, Leo F. Verdonck, Baldeep Wirk, Jean A. Yared, Ryotaro Nakamura, Betul Oran, Bart Scott, and Wael Saber
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative treatment for myelofibrosis. However, the optimal conditioning regimen either with reduced-intensity conditioning (RIC) or myeloablative conditioning (MAC) is not well known. Using the Center for International Blood and Marrow Transplant Research database, we identified adults aged ≥18 years with myelofibrosis undergoing allo-HCT between 2008-2019 and analyzed the outcomes separately in the RIC and MAC cohorts based on the conditioning regimens used. Among 872 eligible patients, 493 underwent allo-HCT using RIC (fludarabine/ busulfan n=166, fludarabine/melphalan n=327) and 379 using MAC (fludarabine/busulfan n=247, busulfan/cyclophosphamide n=132). In multivariable analysis with RIC, fludarabine/melphalan was associated with inferior overall survival (hazard ratio [HR]=1.80; 95% confidenec interval [CI]: 1.15-2.81; P=0.009), higher early non-relapse mortality (HR=1.81; 95% CI: 1.12-2.91; P=0.01) and higher acute graft-versus-host disease (GvHD) (grade 2-4 HR=1.45; 95% CI: 1.03-2.03; P=0.03; grade 3-4 HR=2.21; 95%CI: 1.28-3.83; P=0.004) compared to fludarabine/busulfan. In the MAC setting, busulfan/cyclophosphamide was associated with a higher acute GvHD (grade 2-4 HR=2.33; 95% CI: 1.67-3.25; P
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- 2023
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5. The mutational landscape in chronic myelomonocytic leukemia and its impact on allogeneic hematopoietic cell transplantation outcomes: a Center for Blood and Marrow Transplantation Research (CIBMTR) analysis
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Matthew Mei, Raju Pillai, Soyoung Kim, Noel Estrada-Merly, Michelle Afkhami, Lixin Yang, Zhuo Meng, Muhammad Bilal Abid, Mahmoud Aljurf, Ulrike Bacher, Amer Beitinjaneh, Christopher Bredeson, Jean-Yves Cahn, Jan Cerny, Edward Copelan, Corey Cutler, Zachariah DeFilipp, Miguel Angel Diaz Perez, Nosha Farhadfar, César O. Freytes, Shahinaz M. Gadalla, Siddhartha Ganguly, Robert Peter Gale, Usama Gergis, Michael R. Grunwald, Betty K. Hamilton, Shahrukh Hashmi, Gerhard C. Hildebrandt, Hillard M. Lazarus, Mark Litzow, Reinhold Munker, Hemant S. Murthy, Sunita Nathan, Taiga Nishihori, Sagar S. Patel, David Rizzieri, Sachiko Seo, Mithun Vinod Shah, Melhem Solh, Leo F. Verdonck, Ravi Vij, Ronald M. Sobecks, Betul Oran, Bart L. Scott, Wael Saber, and Ryotaro Nakamura
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Somatic mutations are recognized as an important prognostic factor in chronic myelomonocytic leukemia (CMML). However, limited data are available regarding their impact on outcomes after allogeneic hematopoietic cell transplantation (HCT). In this registry analysis conducted in collaboration with the Center for International Blood and Marrow Transplantation Registry database/sample repository, we identified 313 adult patients with CMML (median age: 64 years, range, 28- 77) who underwent allogeneic HCT during 2001-2017 and had an available biospecimen in the form of a peripheral blood sample obtained prior to the start of conditioning. In multivariate analysis, a CMML-specific prognostic scoring system (CPSS) score of intermediate-2 (HR=1.46, P=0.049) or high (HR=3.22, P=0.0004) correlated significantly with overall survival. When the molecularly informed CPSS-Mol prognostic model was applied, a high CPSS-Mol score (HR=2 P=0.0079) correlated significantly with overall survival. The most common somatic mutations were in ASXL1 (62%), TET2 (35%), KRAS/NRAS (33% combined), and SRSF2 (31%). DNMT3A and TP53 mutations were associated with decreased overall survival (HR=1.70 [95% CI: 1.11-2.60], P=0.0147 and HR=2.72 [95% CI: 1.37-5.39], P=0.0042, respectively) while DNMT3A, JAK2, and TP53 mutations were associated with decreased disease-free survival (HR=1.66 [95% CI: 1.11-2.49], P=0.0138, HR=1.79 [95% CI: 1.06-3.03], P=0.0293, and HR=2.94 [95% CI: 1.50-5.79], P=0.0018, respectively). The only mutation associated with increased relapse was TP53 (HR=2.94, P=0.0201). Nonetheless, the impact of TP53 mutations specifically should be interpreted cautiously given their rarity in CMML. We calculated the goodness of fit measured by Harrell’s C-index for both the CPSS and CPSS-Mol, which were very similar. In summary, via registry data we have determined the mutational landscape in patients with CMML who underwent allogeneic HCT, and demonstrated an association between CPSS-Mol and transplant outcomes although without major improvement in the risk prediction beyond that provided by the CPSS.
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- 2022
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6. Alternative donor transplantation for acute myeloid leukemia in patients aged ≥50 years: young HLA-matched unrelated or haploidentical donor?
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Miguel-Angel Perales, Benjamin Tomlinson, Mei-Jie Zhang, Andrew St. Martin, Amer Beitinjaneh, John Gibson, William Hogan, Natasha Kekre, Hillard Lazarus, David Marks, Joseph McGuirk, Rizwan Romee, Melhem Solh, John E. Wagner, Daniel J. Weisdorf, Marcos de Lima, and Mary Eapen
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
We sought to study whether survival after haploidentical transplantation is comparable to that after matched unrelated donor transplantation for 822 patients aged 50-75 years with acute myeloid leukemia in first or second complete remission. One hundred and ninety-two patients received grafts from haploidentical donors (sibling 25%; offspring 75%) and 631 patients from matched unrelated donors aged 18-40 years. Patients’ and disease characteristics of the two groups were similar except that recipients of matched unrelated donor transplantation were more likely to have poor risk cytogenetics and more likely to receive myeloablative conditioning regimens. Time from documented remission to transplant did not differ by donor type. Five-year overall survival was 32% and 42% after haploidentical and matched unrelated donor transplant, respectively (P=0.04). Multivariable analysis showed higher mortality (hazard ratio 1.27, P=0.04) and relapse (hazard ratio 1.32, P=0.04) after haploidentical transplantation, with similar non-relapse mortality risks. Chronic graft-versus-host disease was higher after matched unrelated donor compared to haploidentical transplantation when bone marrow was the graft (hazard ratio 3.12, P
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- 2020
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7. Effect of donor characteristics on haploidentical transplantation with posttransplantation cyclophosphamide
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Shannon R. McCurdy, Mei-Jie Zhang, Andrew St. Martin, Monzr M. Al Malki, Asad Bashey, Sameh Gaballa, Daniel A. Keesler, Mehdi Hamadani, Maxim Norkin, Miguel-Angel Perales, Ran Reshef, Vanderson Rocha, Rizwan Romee, Melhem Solh, Alvaro Urbano-Ispizua, Edmund K. Waller, Ephraim J. Fuchs, and Mary Eapen
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Specialties of internal medicine ,RC581-951 - Abstract
Abstract: We studied the association between non-HLA donor characteristics (age, sex, donor-recipient relationship, blood group [ABO] match, and cytomegalovirus [CMV] serostatus) and transplant outcomes after T-cell-replete HLA-haploidentical transplantation using posttransplantation cyclophosphamide (PT-Cy) in 928 adults with hematologic malignancy transplanted between 2008 and 2015. Siblings (n = 358) and offspring (n = 450) were the predominant donors, with only 120 patients having received grafts from parents. Although mortality risks were higher with donors aged 30 years or older (hazard ratio, 1.39; P < .0001), the introduction of patient age to the Cox regression model negated the effect of donor age. Two-year survival adjusted for CMV seropositivity, disease, and disease risk index was lower in patients aged 55 to 78 years after transplantation of grafts from donors younger than 30 years (53%) or aged at least 30 years (46%) compared with younger patients who received grafts from donors younger than 30 years (61%) and at least 30 years (60%; P < .0001). Similarly, 2-year survival in patients aged 55 to 78 years was lower after transplantation of grafts from siblings (45%) or offspring (48%) compared with patients aged 18 to 54 years after transplantation of grafts from siblings (62%), offspring (58%), and parents (61%; P < .0001). Graft failure was higher after transplantation of grafts from parents (14%) compared with siblings (6%) or offspring (7%; P = .02). Other non-HLA donor characteristics were not associated with survival or graft failure. The current analyses suggest patient and disease, rather than non-HLA donor characteristics, predominantly influence survival in adults.
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- 2018
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8. Correction: Allogeneic transplantation in elderly patients ≥65 years with non-Hodgkin lymphoma: a time-trend analysis
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Nirav N. Shah, Kwang Woo Ahn, Carlos Litovich, Anna Sureda, Mohamed A. Kharfan-Dabaja, Farrukh T. Awan, Siddhartha Ganguly, Usama Gergis, David Inwards, Reem Karmali, Alexsandr Lazaryan, Lazaros Lekakis, Pashna Munshi, Sunita Nathan, Ayman A. Saad, Melhem Solh, Amir Steinberg, Ravi Vij, William A. Wood, Timothy S. Fenske, Sonali Smith, and Mehdi Hamadani
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2021
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9. Chimeric Antigen Receptor T-Cells: The Future Is Now
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Wassim Mchayleh, Prabhjot Bedi, Rajesh Sehgal, and Melhem Solh
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Chimeric ,cellular ,immunotherapy ,T cell ,Medicine - Abstract
The immune system acting via cancer immune-surveillance is considered a potential target for improving outcomes among some malignancies. The ability to harness immune cells, engineer them and educate them to target cancer cells has changed the paradigm for treating non-Hodgkin’s lymphomas (NHL) and acute lymphoblastic leukemia (ALL). Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable anti-tumor activity against refractory B cell malignancies. Ongoing research aims to expand the scope of this adoptive cell therapy, understanding mechanisms of resistance and reducing toxicity. In this review, we will discuss the current scope of CAR T-cell therapy and ongoing future applications.
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- 2019
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10. Myeloablative Conditioning with PBSC Grafts for T Cell-Replete Haploidentical Donor Transplantation Using Posttransplant Cyclophosphamide
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Scott R. Solomon, Melhem Solh, Lawrence E. Morris, H. Kent Holland, and Asad Bashey
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Relapse is the main cause of treatment failure after nonmyeloablative haploidentical transplant (haplo-HSCT). In an attempt to reduce relapse, we have developed a myeloablative (MA) haplo-HSCT approach utilizing posttransplant cyclophosphamide (PT/Cy) and peripheral blood stem cells as the stem cell source. We summarize the results of two consecutive clinical trials, using a busulfan-based (n=20) and a TBI-based MA preparative regimen (n=30), and analyze a larger cohort of 64 patients receiving MA haplo-HSCT. All patients have engrafted with full donor chimerism and no late graft failures. Grade III-IV acute GVHD and moderate-severe chronic GVHD occurred in 23% and 30%, respectively. One-year NRM was 10%. Predicted three-year overall survival, disease-free survival, and relapse were 53%, 53%, and 26%, respectively, in all patients and 79%, 74%, and 9%, respectively, in patients with a low/intermediate disease risk index (DRI). In multivariate analysis, DRI was the most significant predictor of survival and relapse. Use of TBI (versus busulfan) had no significant impact on survival but was associated with significantly less BK virus-associated hemorrhagic cystitis. We contrast our results with other published reports of MA haplo-HSCT PT/Cy in the literature and attempt to define the comparative utility of MA haplo-HSCT to other methods of transplantation.
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- 2016
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11. Autoimmune Demyelinating Polyneuropathy as a Manifestation of Chronic Graft-versus-Host Disease after Adult Cord Blood Transplantation in a Patient with Chronic Lymphocytic Leukemia
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Fredrick Hogan and Melhem Solh
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Immune mediated demyelinating disease after allogeneic stem cell transplantation is a rare entity with unclear etiology. Acute inflammatory demyelinating polyneuropathy (AIDP) has been reported after related and adult unrelated allogeneic stem cell transplantation but no such case has been reported after unrelated cord blood transplantation. We hereby present the first case of AIDP after double umbilical cord blood transplantation (DUCBT). A 55-year-old man with chronic lymphocytic leukemia (CLL) received a cord blood transplant for relapsed refractory disease with high risk cytogenetics. On day 221, patient presented with skin rash, tingling in both lower extremites, and ascending paralysis that progressed rapidly over the course of 2 days. The workup resulted in a diagnosis of AIDP and administration of intravenous immunoglobulins plus steroids was initiated. Motor and sensory powers were fully recovered and his chronic GVHD was managed for several months with single agent sirolimus.
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- 2014
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12. Extracorporeal photopheresis (ECP) improves overall survival in the treatment of steroid refractory acute graft-versus-host disease (SR aGvHD)
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H. Kent Holland, Asad Bashey, Xu Zhang, Lawrence E. Morris, Chloe Farnham, Melhem Solh, and Scott R. Solomon
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medicine.medical_specialty ,Transplantation ,business.industry ,Cell Biology ,Hematology ,Gastroenterology ,Internal medicine ,Extracorporeal Photopheresis ,Acute graft versus host disease ,Overall survival ,Molecular Medicine ,Immunology and Allergy ,Medicine ,business ,Steroid refractory - Published
- 2022
13. Impact of pre-transplant induction and consolidation cycles on AML allogeneic transplant outcomes: a CIBMTR analysis in 3113 AML patients
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Michael Boyiadzis, Mei-Jie Zhang, Karen Chen, Hisham Abdel-Azim, Muhammad Bilal Abid, Mahmoud Aljurf, Ulrike Bacher, Talha Badar, Sherif M. Badawy, Minoo Battiwalla, Nelli Bejanyan, Vijaya Raj Bhatt, Valerie I. Brown, Paul Castillo, Jan Cerny, Edward A. Copelan, Charles Craddock, Bhagirathbhai Dholaria, Miguel Angel Diaz Perez, Christen L. Ebens, Robert Peter Gale, Siddhartha Ganguly, Lohith Gowda, Michael R. Grunwald, Shahrukh Hashmi, Gerhard C. Hildebrandt, Madiha Iqbal, Omer Jamy, Mohamed A. Kharfan-Dabaja, Nandita Khera, Hillard M. Lazarus, Richard Lin, Dipenkumar Modi, Sunita Nathan, Taiga Nishihori, Sagar S. Patel, Attaphol Pawarode, Wael Saber, Akshay Sharma, Melhem Solh, John L. Wagner, Trent Wang, Kirsten M. Williams, Lena E. Winestone, Baldeep Wirk, Amer Zeidan, Christopher S. Hourigan, Mark Litzow, Partow Kebriaei, Marcos de Lima, Kristin Page, and Daniel J. Weisdorf
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Cancer Research ,Oncology ,Hematology - Published
- 2022
14. Haploidentical bone marrow transplantation in patients with relapsed or refractory severe aplastic anaemia in the USA (BMT CTN 1502): a multicentre, single-arm, phase 2 trial
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Amy E DeZern, Mary Eapen, Juan Wu, Julie-An Talano, Melhem Solh, Blachy J Dávila Saldaña, Chatchada Karanes, Mitchell E Horwitz, Kanwaldeep Mallhi, Sally Arai, Nosha Farhadfar, Elizabeth Hexner, Peter Westervelt, Joseph H Antin, H Joachim Deeg, Eric Leifer, Robert A Brodsky, Brent R Logan, Mary M Horowitz, Richard J Jones, and Michael A Pulsipher
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Adult ,Male ,Adolescent ,Anemia, Aplastic ,Graft vs Host Disease ,Hematology ,Middle Aged ,United States ,Article ,Young Adult ,Humans ,Female ,Diterpenes ,Neoplasm Recurrence, Local ,Child ,Cyclophosphamide ,Immunosuppressive Agents ,Aged ,Bone Marrow Transplantation - Abstract
Relapsed severe aplastic anaemia is a marrow failure disorder with high morbidity and mortality. It is often treated with bone marrow transplantation at relapse post-immunosuppressive therapy, but under-represented minorities often cannot find a suitably matched donor. This study aimed to understand the 1-year overall survival in patients with relapsed or refractory severe aplastic anaemia after haploidentical bone marrow transplantation.We report the outcomes of BMT CTN 1502, a single-arm, phase 2 clinical trial done at academic bone marrow transplantation centres in the USA. Included patients were children and adults (75 years or younger) with severe aplastic anaemia that was refractory (fulfilment of severe aplastic anaemia disease criteria at least 3 months after initial immunosuppressive therapy) or relapsed (initial improvement of cytopenias after first-line immunosuppressive therapy but then a later return to fulfilment of severe aplastic anaemia disease criteria), adequate performance status (Eastern Cooperative Oncology Group score 0 or 1, Karnofsky or Lansky score ≥60%), and the presence of an eligible related haploidentical donor. The regimen used reduced-intensity conditioning (rabbit anti-thymocyte globulin 4·5 mg/kg in total, cyclophosphamide 14·5 mg/kg daily for 2 days, fludarabine 30 mg/mBetween May 1, 2017, and Aug 30, 2020, 32 patients with relapsed or refractory severe aplastic anaemia were enrolled from 14 centres, and 31 underwent bone marrow transplantation. The median age was 24·9 years (IQR 10·4-51·3), and median follow-up was 24·3 months (IQR 12·1-29·2). Of the 31 patients who received a transplant, 19 (61%) were male and 12 (39%) female. 13 (42%) patients were site-reported as non-White, and 19 (61%) were from under-represented racial and ethnic groups; there were four (13%) patients who were Asian, seven (23%) Black, one (3%) Hawaiian/Pacific Islander, and one (3%) more than one race, with seven (23%) patients reporting Hispanic ethnicity. 24 (77%) of 31 patients were alive with engraftment at 1 year, and one (3%) patient alive with autologous recovery. The 1-year overall survival was 81% (95% CI 62-91). The most common grade 3-5 adverse events (seen in seven or more patients) included seven (23%) patients with abnormal liver tests, 15 (48%) patients with cardiovascular changes (including sinus tachycardia, heart failure, pericarditis), ten (32%) patients with gastrointestinal issues, seven (23%) patients with nutritional disorders, and eight (26%) patients with respiratory disorders. Six (19%) deaths, due to disease and unsuccessful bone marrow transplantation, were reported after transplantation.Haploidentical bone marrow transplantation using this approach results in excellent overall survival with minimal GVHD in patients who have not responded to immunosuppressive therapy, and can expand access to bone marrow transplantation across all populations. In clinical practice, this could now be considered a standard approach for salvage treatment of severe aplastic anaemia. Attention to obtaining high cell doses (2·5 × 10US National Heart, Lung, and Blood Institute and US National Cancer Institute.
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- 2022
15. Loncastuximab tesirine in relapsed/refractory high-grade B-cell lymphoma: a subgroup analysis from the LOTIS-2 study
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Juan P. Alderuccio, Weiyun Z. Ai, John Radford, Melhem Solh, Kirit M. Ardeshna, Matthew A. Lunning, Brian T. Hess, Pier L. Zinzani, Anastasios Stathis, Carmelo Carlo-Stella, Mehdi Hamadani, Brad S. Kahl, David Ungar, Turk Kilavuz, Eric Yu, Yajuan Qin, and Paolo F. Caimi
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Benzodiazepines ,Manchester Cancer Research Centre ,ResearchInstitutes_Networks_Beacons/mcrc ,Humans ,Lymphoma, Large B-Cell, Diffuse ,Hematology ,Neoplasm Recurrence, Local ,Antibodies, Monoclonal, Humanized - Published
- 2022
16. Impact of bortezomib‐based versus lenalidomide maintenance therapy on outcomes of patients with high‐risk multiple myeloma
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Naresh Bumma, Binod Dhakal, Raphael Fraser, Noel Estrada‐Merly, Kenneth Anderson, César O. Freytes, Gerhard C. Hildebrandt, Leona Holmberg, Maxwell M. Krem, Cindy Lee, Lazaros Lekakis, Hillard M. Lazarus, Hira Mian, Hemant S. Murthy, Sunita Nathan, Taiga Nishihori, Ricardo Parrondo, Sagar S. Patel, Melhem Solh, Christopher Strouse, David H. Vesole, Shaji Kumar, Muzaffar H. Qazilbash, Nina Shah, Anita D’Souza, and Surbhi Sidana
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Cancer Research ,Oncology - Published
- 2023
17. Metabolic Tumor Volume Predicts Outcomes in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma Treated with Loncastuximab Tesirine in the Lotis-2 Trial
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Juan Pablo Alderuccio, Russ A Kuker, Isildinha M Reis, Muthiah Nachiappan, Brad S. Kahl, Mehdi Hamadani, Weiyun Z. Ai, John Radford, Melhem Solh, Kirit M. Ardeshna, Brian T. Hess, Matthew A. Lunning, Pier Luigi Zinzani, Anastasios Stathis, Carmelo Carlo-Stella, Eric Yu, Paolo F Caimi, Deukwoo Kwon, Izidore S. Lossos, Fei Yang, and Craig H. Moskowitz
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
18. Data from Prognostic Score and Cytogenetic Risk Classification for Chronic Lymphocytic Leukemia Patients: Center for International Blood and Marrow Transplant Research Report
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Jennifer R. Brown, Wael Saber, Edwin Alyea, Ronald Sobecks, Uday Popat, Usama Gergis, Asad Bashey, Richard F. Olsson, Saurabh Chhabra, Taiga Nishihori, Baldeep M. Wirk, Jean Yared, Michael R. Grunwald, Jan Cerny, Bipin N. Savani, Amer Beitinjaneh, Sunita Nathan, Edward A. Copelan, Nakhle Saba, Tamila Kindwall-Keller, Attaphol Pawarode, Brian T. Hill, Harry C. Schouten, Mahmoud Aljurf, Ayman Saad, Nilanjan Ghosh, Mohamed A. Kharfan-Dabaja, Melhem Solh, Jean-Yves Cahn, Yoshihiro Inamoto, Gerhard C. Hildebrandt, Ran Reshef, Hillard Lazarus, Ulrike Bacher, Sid Ganguly, Mehdi Hamadani, David I. Marks, Robert Peter Gale, Gregory A. Hale, Minoo Battiwalla, Miguel-Angel Perales, Sergio A. Giralt, Amelia Langston, Stephen Forman, Joseph McGuirk, Jayesh Mehta, Richard Nash, Edward Agura, Joseph Uberti, Steven Devine, Robert Negrin, William Hogan, Joseph Pidala, Oliver Press, Mazyar Shadman, Mohamed L. Sorror, Joseph H. Antin, Virginia O. Volpe, Matthew S. Davids, Zhen-Huan Hu, Kwang Woo Ahn, and Haesook T. Kim
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Purpose:To develop a prognostic model and cytogenetic risk classification for previously treated patients with chronic lymphocytic leukemia (CLL) undergoing reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT).Experimental Design:We performed a retrospective analysis of outcomes of 606 patients with CLL who underwent RIC allogeneic HCT between 2008 and 2014 reported to the Center for International Blood and Marrow Transplant Research.Results:On the basis of multivariable models, disease status, comorbidity index, lymphocyte count, and white blood cell count at HCT were selected for the development of prognostic model. Using the prognostic score, we stratified patients into low-, intermediate-, high-, and very-high-risk [4-year progression-free survival (PFS) 58%, 42%, 33%, and 25%, respectively, P < 0.0001; 4-year overall survival (OS) 70%, 57%, 54%, and 38%, respectively, P < 0.0001]. We also evaluated karyotypic abnormalities together with del(17p) and found that del(17p) or ≥5 abnormalities showed inferior PFS. Using a multivariable model, we classified cytogenetic risk into low, intermediate, and high (P < 0.0001). When the prognostic score and cytogenetic risk were combined, patients with low prognostic score and low cytogenetic risk had prolonged PFS (61% at 4 years) and OS (75% at 4 years).Conclusions:In this large cohort of patients with previously treated CLL who underwent RIC HCT, we developed a robust prognostic scoring system of HCT outcomes and a novel cytogenetic-based risk stratification system. These prognostic models can be used for counseling patients, comparing data across studies, and providing a benchmark for future interventions. For future study, we will further validate these models for patients receiving targeted therapies prior to HCT.
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- 2023
19. Supplementary Figure 2 from A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody–Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma
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Owen A. O'Connor, Karin Havenith, Joseph Boni, Shui He, David Ungar, Leonard T. Heffner, Melhem Solh, Kirit M. Ardeshna, Jay M. Feingold, Erin Reid, Paolo Caimi, Carmelo Carlo-Stella, John Radford, Mehdi Hamadani, and Brad S. Kahl
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Supplementary Figure 2
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- 2023
20. Supplementary Figure 1 from A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody–Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma
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Owen A. O'Connor, Karin Havenith, Joseph Boni, Shui He, David Ungar, Leonard T. Heffner, Melhem Solh, Kirit M. Ardeshna, Jay M. Feingold, Erin Reid, Paolo Caimi, Carmelo Carlo-Stella, John Radford, Mehdi Hamadani, and Brad S. Kahl
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Supplementary Figure 1
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- 2023
21. Supplementary Data from Prognostic Score and Cytogenetic Risk Classification for Chronic Lymphocytic Leukemia Patients: Center for International Blood and Marrow Transplant Research Report
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Jennifer R. Brown, Wael Saber, Edwin Alyea, Ronald Sobecks, Uday Popat, Usama Gergis, Asad Bashey, Richard F. Olsson, Saurabh Chhabra, Taiga Nishihori, Baldeep M. Wirk, Jean Yared, Michael R. Grunwald, Jan Cerny, Bipin N. Savani, Amer Beitinjaneh, Sunita Nathan, Edward A. Copelan, Nakhle Saba, Tamila Kindwall-Keller, Attaphol Pawarode, Brian T. Hill, Harry C. Schouten, Mahmoud Aljurf, Ayman Saad, Nilanjan Ghosh, Mohamed A. Kharfan-Dabaja, Melhem Solh, Jean-Yves Cahn, Yoshihiro Inamoto, Gerhard C. Hildebrandt, Ran Reshef, Hillard Lazarus, Ulrike Bacher, Sid Ganguly, Mehdi Hamadani, David I. Marks, Robert Peter Gale, Gregory A. Hale, Minoo Battiwalla, Miguel-Angel Perales, Sergio A. Giralt, Amelia Langston, Stephen Forman, Joseph McGuirk, Jayesh Mehta, Richard Nash, Edward Agura, Joseph Uberti, Steven Devine, Robert Negrin, William Hogan, Joseph Pidala, Oliver Press, Mazyar Shadman, Mohamed L. Sorror, Joseph H. Antin, Virginia O. Volpe, Matthew S. Davids, Zhen-Huan Hu, Kwang Woo Ahn, and Haesook T. Kim
- Abstract
Supplementary Material
- Published
- 2023
22. Supplementary Materials from A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody–Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma
- Author
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Owen A. O'Connor, Karin Havenith, Joseph Boni, Shui He, David Ungar, Leonard T. Heffner, Melhem Solh, Kirit M. Ardeshna, Jay M. Feingold, Erin Reid, Paolo Caimi, Carmelo Carlo-Stella, John Radford, Mehdi Hamadani, and Brad S. Kahl
- Abstract
Supplementary Materials
- Published
- 2023
23. Data from A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody–Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma
- Author
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Owen A. O'Connor, Karin Havenith, Joseph Boni, Shui He, David Ungar, Leonard T. Heffner, Melhem Solh, Kirit M. Ardeshna, Jay M. Feingold, Erin Reid, Paolo Caimi, Carmelo Carlo-Stella, John Radford, Mehdi Hamadani, and Brad S. Kahl
- Abstract
Purpose:ADCT-402 (loncastuximab tesirine) is an antibody–drug conjugate comprising a CD19-targeting antibody and pyrrolobenzodiazepine dimers. A first-in-human study evaluated the safety and preliminary clinical activity of loncastuximab tesirine in patients with B-cell non-Hodgkin lymphoma (NHL).Patients and Methods:A multicenter, phase I, dose-escalation and dose-expansion study enrolled patients ages ≥18 years with relapsed/refractory (R/R) B-cell NHL. Patients received loncastuximab tesirine every 3 weeks at doses assigned by a 3+3 dose-escalation design. Dose escalation was used to assess the safety and tolerability of loncastuximab tesirine to determine the dose for expansion. Secondary objectives evaluated clinical activity, characterized the pharmacokinetic profile, and evaluated antidrug antibodies.Results:During dose escalation, 88 patients with R/R B-cell NHL were treated with loncastuximab tesirine at doses 15 to 200 μg/kg. Treatment-emergent adverse events (TEAEs) were experienced by 87/88 (98.9%) patients. Most common TEAEs (≥20% of patients) were hematologic abnormalities, fatigue, edema, liver test abnormalities, nausea, rash, and dyspnea. Grade ≥3 TEAEs (≥5% of patients) included hematologic abnormalities, liver test abnormalities, fatigue, and dyspnea. Overall response rate at doses ≥120 μg/kg was 59.4% (41 of 69 patients; 40.6% complete response; 18.8% partial response). Median duration of response, progression-free survival, and overall survival (all doses) were 4.8, 5.5, and 11.6 months, respectively. Drug exposure increased with increasing dose, showing moderate accumulation with multiple doses ≥150 μg/kg. There was no evidence of immunogenicity.Conclusions:Loncastuximab tesirine had promising activity with acceptable safety in this dose-escalation study. A phase II study with initial dosing at 150 μg/kg has been initiated based on these results.
- Published
- 2023
24. Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML
- Author
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Vijaya Raj Bhatt, Rodrigo Martino, Martin S. Tallman, Rafael Madero-Marroquin, Siddhartha Ganguly, Michael R. Grunwald, Mahmoud Aljurf, Stefan O. Ciurea, Ankit Kansagra, Taiga Nishihori, Brenda M. Sandmaier, Jacob M. Rowe, Alexandra Gomez-Arteaga, Amer Assal, Jan Cerny, Gerhard C. Hildebrandt, Shahinaz M. Gadalla, Jonathan Sanchez, Shahrukh K. Hashmi, Mei-Jie Zhang, Christopher Bredeson, Hillard M. Lazarus, Leo F. Verdonck, Akshay Sharma, Paul Castillo, Richard F. Olsson, Wael Saber, Fotios V. Michelis, Sachiko Seo, Kamal Menghrajani, Christopher S. Hourigan, Hongtao Liu, Ran Reshef, Michael Byrne, Sunita Nathan, Partow Kebriaei, Hai-Lin Wang, Lohith Gowda, Melhem Solh, Maxwell M. Krem, Zachariah DeFilipp, Yanming Zhang, Sherif M Badawy, Robert Peter Gale, Nosha Farhadfar, Ulrike Bacher, David A. Rizzieri, Nelli Bejanyan, Christopher G. Kanakry, Bipin N. Savani, Mark R. Litzow, Khalid Bo-Subait, Daniel J. Weisdorf, Saurabh Chhabra, Farhad Khimani, and Celalettin Ustun
- Subjects
Oncology ,medicine.medical_specialty ,biology ,business.industry ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,Cytogenetics ,Myeloid leukemia ,Hematology ,Disease ,Leukemia, Myeloid, Acute ,Increased risk ,KMT2A ,Cell transplantation ,Recurrence ,hemic and lymphatic diseases ,Internal medicine ,Overall survival ,medicine ,biology.protein ,Humans ,610 Medicine & health ,Risk classification ,business - Abstract
Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes in patients with acute myeloid leukemia (AML). We evaluated 8709 patients with AML from the CIBMTR database, and after selection and manual curation of the cytogenetics data, 3779 patients in first complete remission were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis detected an increased risk of relapse for patients with KMT2A-rearranged or adverse-risk AML as compared to those with intermediate-risk disease (hazards ratio [HR], 1.27; P = .01; HR, 1.71; P < .001, respectively). Leukemia-free survival was similar for patients with KMT2A rearrangement or adverse risk (HR, 1.26; P = .002, and HR, 1.47; P < .001), as was overall survival (HR, 1.32; P < .001, and HR, 1.45; P < .001). No differences in outcome were detected when patients were stratified by KMT2A fusion partner. This study is the largest conducted to date on post-HCT outcomes in AML, with manually curated cytogenetics used for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A-rearranged and adverse-risk disease.
- Published
- 2022
25. Outcomes of Cryopreserved Vs Fresh Haploidentical Allogeneic Donor Grafts Using Post-Transplant Cyclophosphamide (PTCy) for Gvhd Prophylaxis
- Author
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Lizamarie Bachier, Xu Zhang, Katelin Jackson, Stacey Brown, Scott R. Solomon, Asad Bashey, Melhem Solh, Lawrence E Morris, and H. Kent Holland
- Subjects
Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Published
- 2023
26. Effect of time to relapse on overall survival in patients with mantle cell lymphoma following autologous haematopoietic cell transplantation
- Author
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Mazyar Shadman, Annie Im, Sonali M. Smith, Sai Ravi Pingali, Mehdi Hamadani, Mohamed A. Kharfan-Dabaja, Julie M. Vose, Narendranath Epperla, Paul Shaughnessy, Claudio G. Brunstein, Carlos Litovich, Peter A. Riedell, Brian T. Hill, Alex F. Herrera, David J. Inwards, Melhem Solh, Patrick J. Stiff, Kwang Woo Ahn, John M. McCarty, Amanda F. Cashen, John Lister, Craig S. Sauter, and Jonathon B. Cohen
- Subjects
Oncology ,medicine.medical_specialty ,Multivariate analysis ,business.industry ,Hazard ratio ,Time to relapse ,Hematology ,medicine.disease ,Lymphoma ,Haematopoiesis ,Internal medicine ,medicine ,Overall survival ,In patient ,Mantle cell lymphoma ,business - Abstract
In young and fit patients with mantle cell lymphoma (MCL), intensive induction therapy followed by a consolidative autologous haematopoietic cell transplant (autoHCT) is the standard of care in the front-line setting. Recently, time-to-event analysis has emerged as an important risk assessment tool in lymphoma, though its impact in MCL is not well defined. We utilized the Center for International Blood and Marrow Transplant Research database to evaluate the effect of post-autoHCT time to relapse on overall survival (OS) over time in 461 patients who underwent autoHCT within 12 months of MCL diagnosis. On multivariate analysis, the impact of relapse on OS was greatest at the six-month [hazard ratio (HR) = 7·68], 12-month (HR = 6·68), and 18-month (HR = 5·81) landmark timepoints. Using a dynamic landmark model we demonstrate that adjusted OS at five years following each landmark timepoint improved with time for relapsing and non-relapsing patients. Furthermore, early relapse (
- Published
- 2021
27. Let’s Get Serial: Detection and Monitoring of Mucormycosis in Hematopoietic Stem Cell Transplant Recipients with the Karius Test™
- Author
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Eva Karam, Asad Bashey, H. Kent Holland, Lawrence E Morris, Melhem Solh, Scott R. Solomon, Asim Ahmed, and Matthew Smollin
- Subjects
Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Published
- 2022
28. Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B-cell non-Hodgkin lymphoma
- Author
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Melhem Solh, Karin Havenith, Jay Feingold, Brad S. Kahl, Erin Reid, Luqiang Wang, Carmelo Carlo-Stella, Leonard T. Heffner, John Radford, Owen A. O'Connor, Paolo Caimi, William Townsend, Joseph Boni, Kirit M. Ardeshna, David Ungar, Yajuan Gu Qin, and Mehdi Hamadani
- Subjects
medicine.medical_specialty ,Lymphoid Neoplasia ,Manchester Cancer Research Centre ,Lymphoma ,business.industry ,ResearchInstitutes_Networks_Beacons/mcrc ,Immunology ,Follicular lymphoma ,Salvage therapy ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Gastroenterology ,Pharmacokinetics ,Refractory ,hemic and lymphatic diseases ,Internal medicine ,medicine ,B-Cell Non-Hodgkin Lymphoma ,Humans ,Mantle cell lymphoma ,business ,Diffuse large B-cell lymphoma - Abstract
The prognosis for patients with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL) remains poor, with a need for alternatives to current salvage therapies. Loncastuximab tesirine (ADCT-402) is an antibody-drug conjugate comprising a humanized anti-CD19 monoclonal antibody conjugated to a pyrrolobenzodiazepine dimer toxin. Presented here are final results of a phase 1 dose-escalation and dose-expansion study in patients with R/R B-NHL. Objectives were to determine the maximum tolerated dose (MTD) and recommended dose(s) for expansion and evaluate safety, clinical activity, pharmacokinetics, and immunogenicity of loncastuximab tesirine. Overall, 183 patients received loncastuximab tesirine, with 3 + 3 dose escalation at 15 to 200 µg/kg and dose expansion at 120 and 150 µg/kg. Dose-limiting toxicities (all hematologic) were reported in 4 patients. The MTD was not reached, although cumulative toxicity was higher at 200 µg/kg. Hematologic treatment-emergent adverse events were most common, followed by fatigue, nausea, edema, and liver enzyme abnormalities. Overall response rate (ORR) in evaluable patients was 45.6%, including 26.7% complete responses (CRs). ORRs in patients with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, and follicular lymphoma were 42.3%, 46.7%, and 78.6%, respectively. Median duration of response in all patients was 5.4 months and not reached in patients with DLBCL (doses ≥120 µg/kg) who achieved a CR. Loncastuximab tesirine had good stability in serum, notable antitumor activity, and an acceptable safety profile, warranting continued study in B-NHL. The recommended dose for phase 2 was determined as 150 µg/kg every 3 weeks for 2 doses followed by 75 µg/kg every 3 weeks. This trial was registered at www.clinicaltrials.gov as #NCT02669017.
- Published
- 2021
29. Transition from Initial Therapy to Hematopoietic Cell Transplantation for Non-Favorable Risk Acute Leukemia and MDS Patients in the Era of Haploidentical Donor Availability: Assessment of Efficacy, Barriers and Racial Disparities in 269 Consecutive Patients Treated in an Integrated Leukemia/HCT Program
- Author
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Asad Bashey, Xu Zhang, Melhem Solh, H. Kent Holland, Lawrence E. Morris, Lizamarie Bachier-Rodriguez, and Scott R. Solomon
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
30. Effect of CMV Reactivation and Letermovir Use on Chronic Gvhd Incidence Following Haploidentical Donor Transplantation with Post-Transplant Cyclophosphamide
- Author
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Scott R. Solomon, Lizamarie Bachier-Rodriguez, Xu Zhang, H. Kent Holland, Lawrence E. Morris, Asad Bashey, and Melhem Solh
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
31. Differences in Patterns of Infections Among Allogeneic Hematopoietic Cell Transplant Patients Receiving Letermovir Prophylaxis for Cytomegalovirus
- Author
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Melhem Solh, Scott R. Solomon, Xu Zhang, Lawrence E. Morris, Lizamarie Bachier-Rodriguez, H. Kent Holland, and Asad Bashey
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
32. TBI-Based Myeloablative Conditioning Prior to Haploidentical Versus Matched Donor Transplantation for Acute Lymphoblastic Leukemia
- Author
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Scott R. Solomon, Lizamarie Bachier-Rodriguez, Xu Zhang, Asad Bashey, Lawrence E. Morris, H. Kent Holland, and Melhem Solh
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
33. Frequency and Clinical Significance of Mixed T-Cell Chimerism Following Myeloablative Busulfan and Cyclophosphamide Conditioning in HLA -Matched Donor Transplants for Myeloid Malignancies: An Analysis of 179 Patients Transplanted at a Single Center
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Asad Bashey, Xu Zhang, Scott R. Solomon, Lizamarie Bachier-Rodriguez, H. Kent Holland, Lawrence E. Morris, and Melhem Solh
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
34. Phase II Study of PD-1 Blockade Following Fludarabine/Melphalan-Based Autologous Transplantation for Acute Myeloid Leukemia Patients Ineligible for Allogeneic Transplant
- Author
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Scott R. Solomon, Melhem Solh, Lawrence E. Morris, H. Kent Holland, Lizamarie Bachier-Rodriguez, Xu Zhang, Caitlin Guzowski, Katelin C Jackson, Stacey Brown, and Asad Bashey
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
35. A Phase 1b Open-Label Study of Loncastuximab Tesirine in Combination with Other Anticancer Agents in Patients with Relapsed or Refractory (R/R) B-Cell Non-Hodgkin Lymphoma (LOTIS-7)
- Author
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Brian T. Hess, Graham P. Collins, Melhem Solh, Mitul Gandhi, Ying Wang, Yajuan Qin, Eric Yu, and Pier Luigi Zinzani
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
36. Vitalize Trial: A Phase 2b, Open-Label, Multicenter, Randomized Parallel-Group, Two-Stage, Study of the Novel Immunotherapeutic, Maveropepimut-S, and Pembrolizumab with and without Intermittent Low-Dose Cyclophosphamide, in Subjects with Relapsed/Refractory Diffuse Large B-Cell Lymphoma
- Author
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Matthew J. Matasar, Eric Lee, Sophie Leitch, Melhem Solh, Jennifer Teti, Kabir Mody, Stephan Fiset, and Jeremy Graff
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
37. HLA Evolutionary Divergence (HED) Informs the Effect of HLA-B-Loci Mismatch on Relapse and Disease Free Survival after Haploidentical Hematopoietic Cell Transplantation (Haplo) with Post-Transplant Cyclophosphamide (PTCY)
- Author
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Melhem Solh, Michael T Aubrey, Xu Zhang, Asad Bashey, Brian M Freed, Christina L Roark, Lizamarie Bachier-Rodriguez, Lawrence E. Morris, H. Kent Holland, and Scott R. Solomon
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
38. Graft-Versus-Host Disease (GVHD) after Post-Transplant Cyclophosphamide or Conventional GVHD Prophylaxis: Same Title, Different Song
- Author
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Melhem, Solh
- Subjects
Transplantation ,Hematopoietic Stem Cell Transplantation ,Graft vs Host Disease ,Humans ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology ,Cyclophosphamide - Published
- 2022
39. Alternative donor transplantation for myelodysplastic syndromes: haploidentical relative and matched unrelated donors
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Melhem Solh, Biju George, Mariam H Johnson, Vikas Gupta, Daniel J. Weisdorf, Michael R. Grunwald, Wael Saber, Andrew St. Martin, Minoo Battiwalla, Christopher G. Kanakry, Rohtesh S. Mehta, Mary Eapen, Corey Cutler, Christopher Bredeson, Ryotaro Nakamura, Filippo Milano, Taiga Nishihori, Edward A. Copelan, Asad Bashey, Alberto Mussetti, Hany Elmariah, and Mei-Jie Zhang
- Subjects
Melphalan ,medicine.medical_specialty ,Transplantation Conditioning ,Graft vs Host Disease ,Gastroenterology ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Transplantation ,business.industry ,Histocompatibility Testing ,Myelodysplastic syndromes ,Hematology ,medicine.disease ,Fludarabine ,Calcineurin ,Regimen ,surgical procedures, operative ,Graft-versus-host disease ,Myelodysplastic Syndromes ,Unrelated Donors ,business ,Busulfan ,medicine.drug - Abstract
We compared outcomes in 603 patients with myelodysplastic syndrome (MDS) after HLA-haploidentical relative (n = 176) and HLA-matched unrelated (n = 427) donor hematopoietic cell transplantation (HCT) from 2012 to 2017, using the Center for International Blood and Marrow Transplant Research database. All transplantations used reduced-intensity conditioning regimens. Total-body irradiation plus cyclophosphamide and fludarabine was the predominant regimen for HLA-haploidentical relative donor HCT, and graft-versus-host disease (GVHD) prophylaxis was uniformly posttransplantation cyclophosphamide, calcineurin inhibitor, and mycophenolate. Fludarabine with busulfan or melphalan was the predominant regimen for HLA-matched unrelated donor HCT, and GVHD prophylaxis was calcineurin inhibitor with mycophenolate or methotrexate. Results of multivariate analysis revealed higher relapse (hazard ratio [HR], 1.56; P = .0055; 2-year relapse rate, 48% vs 33%) and lower disease-free survival (DFS) rates after HLA-haploidentical relative donor HCT (HR, 1.29; P = .042; 2-year DFS, 29% vs 36%). However, overall survival (OS) rates did not differ between donor type (HR, 0.94; P = .65; 2-year OS, 46% for HLA-haploidentical and 44% for HLA-matched unrelated donor HCT) because of mortality associated with chronic GVHD. Acute grade 2 to 4 GVHD (HR, 0.44; P < .0001) and chronic GVHD (HR, 0.36; P < .0001) were lower after HLA-haploidentical relative donor HCT. By 2 years, probability of death resulting from chronic GVHD was lower after HLA-haploidentical relative compared with HLA-matched unrelated donor HCT (6% vs 21%), negating any potential survival advantage from better relapse control. Both donor types extend access to transplantation for patients with MDS; strategies for better relapse control are desirable for HLA-haploidentical relative donor HCT, and effective GVHD prophylaxis regimens are needed for unrelated donor HCT.
- Published
- 2021
40. Outpatient Allogeneic Hematopoietic Cell Transplantation (HCT) in the Eighth Decade and Beyond: Time to Think Outside the BMT Unit
- Author
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Melhem Solh, Scott R. Solomon, H. Kent Holland, Xu Zhang, Lawrence E Morris, Lizamarie Bachier, and Asad Bashey
- Subjects
Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Published
- 2023
41. The Transplant Evaluation Rating Scale predicts overall survival after allogeneic hematopoietic stem cell transplantation
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Lawrence E. Morris, Dawn Speckhart, Asad Bashey, Scott R. Solomon, Melhem Solh, Xu Zhang, and H. Kent Holland
- Subjects
Subset Analysis ,Transplantation ,medicine.medical_specialty ,Transplantation Conditioning ,business.industry ,medicine.medical_treatment ,Hematopoietic Stem Cell Transplantation ,food and beverages ,Hematology ,Hematopoietic stem cell transplantation ,Disease-Free Survival ,Recurrence ,Rating scale ,Internal medicine ,Allogeneic hsct ,Overall survival ,medicine ,Humans ,Transplantation, Homologous ,Nonrelapse mortality ,business ,human activities ,Psychosocial - Abstract
To evaluate the impact of psychosocial risks on post–hematopoietic stem cell transplantation (HSCT) outcomes, we prospectively conducted psychosocial assessment of 556 consecutive allogeneic HSCT patients who received their first allogeneic transplant at our center between 2003 and 2017. The Transplant Evaluation Rating Scale (TERS) score was prospectively assessed by a psychologist before transplantation, and patients were categorized as low, intermediate, or high risk based on their TERS score. Patients in the high-risk TERS group had significantly longer hospital stays during the first 180 days and 1 year post–allogeneic HSCT compared with the low-risk group (16 vs 13 and 21 vs 16 days; P = .05 and .02, respectively). The survival estimates for low-, intermediate-, and high-risk TERS groups at 3 year were as follows: overall survival (OS), 73%, 60%, and 65%; disease-free survival (DFS), 63%, 55%, and 60%; nonrelapse mortality (NRM), 11%, 20%, and 17%; and relapse, 26%, 25%, and 23%, respectively. In a multivariable analysis, intermediate- and high-risk TERS scores predicted for inferior OS, similar DFS, and higher NRM compared with low-risk TERS score. In a subset analysis of patients with low/intermediate risk per Disease Risk Index, multivariable analysis showed that high- and intermediate-risk TERS scores predicted for significantly worse OS, worse DFS, higher NRM, and similar relapse rates compared with low-risk TERS score. Our findings show that psychosocial factors as measured by TERS score are strong predictors of morbidity and mortality after HSCT among patients with low/intermediate disease risk.
- Published
- 2020
42. Comparison of outcomes of HCT in blast phase of BCR-ABL1− MPN with de novo AML and with AML following MDS
- Author
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Wael Saber, Ann E. Woolfrey, Tamila L. Kindwall-Keller, Uday R. Popat, Melhem Solh, Mahmoud Aljurf, Robert Peter Gale, Ryotaro Nakamura, Taiga Nishihori, Bipin N. Savani, Mark R. Litzow, Amer Beitinjaneh, Rammurti T. Kamble, Richard F. Olsson, Sachiko Seo, Jean A. Yared, Jeff Szer, Jane L. Liesveld, Usama Gergis, Betty K. Hamilton, Zhen-Huan Hu, Siddhartha Ganguly, Jan Cerny, Soyoung Kim, Jean-Yves Cahn, Edward A. Copelan, Edwin P. Alyea, Leo F. Verdonck, Biju George, Shahrukh K. Hashmi, Shahinaz M. Gadalla, Aaron T. Gerds, Ying Liu, Bart L. Scott, Gerhard C. Hildebrandt, Baldeep Wirk, Vikas Gupta, Ronald Sobecks, Richard T. Maziarz, Hillard M. Lazarus, David A. Rizzieri, and Ulrike Bacher
- Subjects
Oncology ,medicine.medical_specialty ,Hematology ,Myeloid ,business.industry ,medicine.medical_treatment ,Myelodysplastic syndromes ,Hazard ratio ,food and beverages ,Hematopoietic stem cell transplantation ,medicine.disease ,Transplantation ,03 medical and health sciences ,Leukemia ,0302 clinical medicine ,medicine.anatomical_structure ,hemic and lymphatic diseases ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Myelofibrosis ,business ,030215 immunology - Abstract
Comparative outcomes of allogeneic hematopoietic cell transplantation (HCT) for BCR-ABL1− myeloproliferative neoplasms (MPNs) in blast phase (MPN-BP) vs de novo acute myeloid leukemia (AML), and AML with prior myelodysplastic syndromes (MDSs; post-MDS AML), are unknown. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we compared HCT outcomes in 177 MPN-BP patients with 4749 patients with de novo AML, and 1104 patients with post-MDS AML, using multivariate regression analysis in 2 separate comparisons. In a multivariate Cox model, no difference in overall survival (OS) or relapse was observed in patients with MPN-BP vs de novo AML with active leukemia at HCT. Patients with MPN-BP in remission had inferior OS in comparison with de novo AML in remission (hazard ratio [HR], 1.40 [95% confidence interval [CI], 1.12-1.76]) due to higher relapse rate (HR, 2.18 [95% CI, 1.69-2.80]). MPN-BP patients had inferior OS (HR, 1.19 [95% CI, 1.00-1.43]) and increased relapse (HR, 1.60 [95% CI, 1.31-1.96]) compared with post-MDS AML. Poor-risk cytogenetics were associated with increased relapse in both comparisons. Peripheral blood grafts were associated with decreased relapse in MPN-BP and post-MDS AML (HR, 0.70 [95% CI, 0.57-0.86]). Nonrelapse mortality (NRM) was similar between MPN-BP vs de novo AML, and MPN-BP vs post-MDS AML. Total-body irradiation–based myeloablative conditioning was associated with higher NRM in both comparisons. Survival of MPN-BP after HCT is inferior to de novo AML in remission and post-MDS AML due to increased relapse. Relapse-prevention strategies are required to optimize HCT outcomes in MPN-BP.
- Published
- 2020
43. Relapse and Disease-Free Survival in Patients With Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation Using Older Matched Sibling Donors vs Younger Matched Unrelated Donors
- Author
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Guru Subramanian Guru Murthy, Soyoung Kim, Zhen-Huan Hu, Noel Estrada-Merly, Muhammad Bilal Abid, Mahmoud Aljurf, Ulrike Bacher, Sherif M. Badawy, Amer Beitinjaneh, Chris Bredeson, Jean-Yves Cahn, Jan Cerny, Miguel Angel Diaz Perez, Nosha Farhadfar, Robert Peter Gale, Siddhartha Ganguly, Usama Gergis, Gerhard C. Hildebrandt, Michael R. Grunwald, Shahrukh Hashmi, Nasheed M. Hossain, Matt Kalaycio, Rammurti T. Kamble, Mohamed A. Kharfan-Dabaja, Betty Ky Hamilton, Hillard M. Lazarus, Jane Liesveld, Mark Litzow, David I. Marks, Hemant S. Murthy, Sunita Nathan, Aziz Nazha, Taiga Nishihori, Sagar S. Patel, Attaphol Pawarode, David Rizzieri, Bipin Savani, Sachiko Seo, Melhem Solh, Celalettin Ustun, Marjolein van der Poel, Leo F. Verdonck, Ravi Vij, Baldeep Wirk, Betul Oran, Ryotaro Nakamura, Bart Scott, Wael Saber, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, and MUMC+: MA Hematologie (9)
- Subjects
Adult ,Male ,Cancer Research ,Transplantation Conditioning ,BLOOD ,IMPACT ,BONE-MARROW ,Graft vs Host Disease ,ACUTE MYELOID-LEUKEMIA ,Disease-Free Survival ,Cohort Studies ,AGE ,Humans ,610 Medicine & health ,Aged ,Retrospective Studies ,Original Investigation ,Siblings ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,STEM ,RECIPIENTS ,Oncology ,Myelodysplastic Syndromes ,Neoplasm Recurrence, Local ,Unrelated Donors ,SYSTEM - Abstract
Importance Matched sibling donors (MSDs) are preferred for allogeneic hematopoietic cell transplantation (allo-HCT) in myelodysplastic syndrome even if they are older. However, whether older MSDs or younger human leukocyte antigen-matched unrelated donors (MUDs) are associated with better outcomes remains unclear. Objective To investigate whether allo-HCT for myelodysplastic syndrome using younger MUDs would be associated with improved disease-free survival and less relapse compared with older MSDs. Design, Setting, and Participants This retrospective cohort study assessed data reported to the Center for International Blood and Marrow Transplant Research database from 1761 adults 50 years or older with myelodysplastic syndrome who underwent allo-HCT using an older MSD or younger MUD between January 1, 2011, and December 31, 2017, with a median follow-up of 48 months. Data analysis was performed from January 8, 2019, to December 30, 2020. Interventions/Exposures Allo-HCT from an older MSD (donor age ���50 years) or a younger MUD (donor age ���35 years). Main Outcomes and Measures The primary outcome was disease-free survival. Secondary outcomes were overall survival, relapse, nonrelapse mortality, acute graft-vs-host disease (GVHD), chronic GVHD, and GVHD-free relapse-free survival. Results Of 1761 patients (1162 [66%] male; median [range] age, 64.9 [50.2-77.6] years in the MSD cohort and 66.5 [50.4-80.9] years in MUD cohort), 646 underwent allo-HCT with an older MSD and 1115 with a younger MUD. In multivariable analysis, the rate of disease-free survival was significantly lower in allo-HCTs with older MSDs compared with younger MUDs (hazard ratio [HR], 1.17; 95% CI, 1.02-1.34; P���=���.02), whereas the difference in overall survival rate of allo-HCT with younger MUDs vs older MSDs was not statistically significant (HR, 1.13; 95% CI, 0.98-1.29; P���=���.07). Allo-HCT with older MSDs was associated with significantly higher relapse (HR, 1.62; 95% CI, 1.32-1.97; P���
- Published
- 2022
44. Correction to: An adapted European LeukemiaNet genetic risk stratification for acute myeloid leukemia patients undergoing allogeneic hematopoietic cell transplant. A CIBMTR analysis
- Author
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Antonio M. Jimenez Jimenez, Marcos De Lima, Krishna V. Komanduri, Trent P. Wang, Mei-Jie Zhang, Karen Chen, Hisham Abdel-Azim, Muhammad Bilal Abid, Mahmoud Aljurf, Hassan Alkhateeb, Amer Assal, Ulrike Bacher, Frédéric Baron, Minoo Battiwalla, Amer Beitinjaneh, Nelli Bejanyan, Vijaya Raj Bhatt, Michael Byrne, Jean-Yves Cahn, Mitchell Cairo, Paul Castillo, Edward Copelan, Zachariah DeFilipp, Miguel Angel Diaz Perez, Mahmoud Elsawy, Robert Peter Gale, Biju George, Michael R. Grunwald, Gerhard C. Hildebrandt, William J. Hogan, Christopher G. Kanakry, Ankit Kansagra, Mohamed A. Kharfan-Dabaja, Nandita Khera, Maxwell M. Krem, Aleksandr Lazaryan, Joseph Maakaron, Rodrigo Martino, Joseph McGuirk, Fotios V. Michelis, Giuseppe Milone, Asmita Mishra, Hemant S. Murthy, Alberto Mussetti, Sunita Nathan, Taiga Nishihori, Richard F. Olsson, Neil Palmisiano, Sagar Patel, Ayman Saad, Sachiko Seo, Akshay Sharma, Melhem Solh, Leo F. Verdonck, Baldeep Wirk, Jean A. Yared, Mark Litzow, Partow Kebriaei, Christopher S. Hourigan, Wael Saber, and Daniel Weisdorf
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Transplantation ,Hematology ,610 Medicine & health - Published
- 2022
- Full Text
- View/download PDF
45. Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide
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Siddhartha Ganguly, Andrew Daly, Tracey A. O'Brien, Melhem Solh, Steven Z. Pavletic, Rammurti T. Kamble, Leslie Lehmann, Tao Wang, Takanori Teshima, Amer Beitinjaneh, Miguel Pérez, Mahmoud Aljurf, Mukta Arora, John L. Wagner, Medhat Askar, Marjolein van der Poel, Madan Jagasia, Rabi Hanna, Alvaro Urbano-Ispizua, Ravi Vij, Armin Rashidi, Taiga Nishihori, Catherine J. Lee, A. Samer Al-Homsi, Vijaya Raj Bhatt, Michael T. Hemmer, Roger Strair, Hannah Choe, Joseph Pidala, Jeffery J. Auletta, Hisham Abdel-Azim, Vaibhav Agrawal, Shahinaz M. Gadalla, Stefan O. Ciurea, S Spellman, Margaret L. MacMillan, Rodrigo Martino, Jean-Yves Cahn, Mitchell S. Cairo, Basem M. William, Rizwan Romee, Jean A. Yared, Navneet S. Majhail, Annie Im, Usama Gergis, Mohamed A. Kharfan-Dabaja, Richard F. Olsson, Sagar S. Patel, Baldeep Wirk, Peiman Hematti, Michael Byrne, Asad Bashey, Hemant S. Murthy, Betty K. Hamilton, Muna Qayed, Pooja Khandelwal, Robert Peter Gale, Saurabh Chhabra, Gerhard C. Hildebrandt, Jan Cerny, Sachiko Seo, Roger H. Herzig, Nosha Farhadfar, Deepesh Lad, Hélène Schoemans, Akshay Sharma, Tim Prestidge, Lazaros J. Lekakis, Daniel J. Weisdorf, Paul Castillo, Miguel-Angel Perales, Interne Geneeskunde, MUMC+: MA Hematologie (9), and RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy
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Adult ,medicine.medical_specialty ,Transplantation Conditioning ,Cyclophosphamide ,Immunology ,Graft vs Host Disease ,Disease ,ACUTE MYELOID-LEUKEMIA ,PERIPHERAL-BLOOD ,ACUTE GVHD ,Gastroenterology ,Article ,HEMATOLOGIC MALIGNANCIES ,03 medical and health sciences ,0302 clinical medicine ,CONDITIONING REGIMEN ,Risk Factors ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Humans ,Transplantation ,OUTCOMES ,Science & Technology ,business.industry ,Incidence (epidemiology) ,DONOR TRANSPLANTATION ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Hematology ,medicine.disease ,RELAPSE-FREE SURVIVAL ,BONE-MARROW-TRANSPLANTATION ,Graft-versus-host disease ,medicine.anatomical_structure ,surgical procedures, operative ,030220 oncology & carcinogenesis ,BLOOD STEM-CELLS ,Bone marrow ,business ,Life Sciences & Biomedicine ,030215 immunology ,medicine.drug - Abstract
Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P = .002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P < .001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus
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- 2020
46. 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
47. 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.
- Published
- 2020
48. Alternative donor transplantation for acute myeloid leukemia in patients aged ≥50 years: young HLA-matched unrelated or haploidentical donor?
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David I. Marks, John Gibson, Marcos De Lima, Amer Beitinjaneh, Mary Eapen, Andrew St. Martin, Natasha Kekre, John E. Wagner, Benjamin Tomlinson, Daniel J. Weisdorf, Miguel-Angel Perales, William J. Hogan, Hillard M. Lazarus, Melhem Solh, Joseph P. McGuirk, Mei-Jie Zhang, and Rizwan Romee
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Adult ,Acute Myeloid Leukemia ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,Offspring ,Graft vs Host Disease ,Human leukocyte antigen ,Disease ,Article ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Transplantation, Homologous ,Humans ,Sibling ,Aged ,Retrospective Studies ,business.industry ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Hematology ,Middle Aged ,3. Good health ,Transplantation ,Leukemia, Myeloid, Acute ,Editorial ,medicine.anatomical_structure ,surgical procedures, operative ,Transplantation, Haploidentical ,Bone marrow ,business ,Unrelated Donors ,030215 immunology - Abstract
We sought to study whether survival after haploidentical transplantation is comparable to that after matched unrelated donor transplantation for 822 patients aged 50-75 years with acute myeloid leukemia in first or second complete remission. One hundred and ninety-two patients received grafts from haploidentical donors (sibling 25%; offspring 75%) and 631 patients from matched unrelated donors aged 18-40 years. Patients' and disease characteristics of the two groups were similar except that recipients of matched unrelated donor transplantation were more likely to have poor risk cytogenetics and more likely to receive myeloablative conditioning regimens. Time from documented remission to transplant did not differ by donor type. Five-year overall survival was 32% and 42% after haploidentical and matched unrelated donor transplant, respectively (P=0.04). Multivariable analysis showed higher mortality (hazard ratio 1.27, P=0.04) and relapse (hazard ratio 1.32, P=0.04) after haploidentical transplantation, with similar non-relapse mortality risks. Chronic graft-versus-host disease was higher after matched unrelated donor compared to haploidentical transplantation when bone marrow was the graft (hazard ratio 3.12, P
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- 2020
49. Who Is a Better Donor for Recipients of Allogeneic Hematopoietic Cell Transplantation: A Young HLA-Mismatched Haploidentical Relative or an Older Fully HLA-Matched Sibling or Unrelated Donor?
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Justin LaPorte, Melhem Solh, Scott R. Solomon, Xu Zhang, Eva Karam, Asad Bashey, H. Kent Holland, and Lawrence E. Morris
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Adult ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,Cyclophosphamide ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Lower risk ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Aged ,Transplantation ,Univariate analysis ,Donor selection ,business.industry ,Siblings ,Incidence (epidemiology) ,Hematopoietic Stem Cell Transplantation ,Hematology ,Transplant-Related Mortality ,Middle Aged ,Female ,Unrelated Donors ,business ,medicine.drug - Abstract
T cell replete HLA-mismatched haploidentical transplantation (HIDT) with post-transplant cyclophosphamide is increasingly becoming an acceptable treatment approach for patients lacking timely access to a suitably matched related donor transplant (MRDT) or matched unrelated donor transplant (MUDT). Multiple recent registry and single-center studies have shown comparable overall survival (OS) and disease-free survival (DFS) rates among HIDT, MRDT, and MUDT with a significantly lower risk of acute and chronic graft-versus-host disease (GVHD) among HIDT recipients. Candidates for allogeneic hematopoietic stem cell transplantation (HSCT) often have access to multiple donor sources, and a relevant question is whether outcomes can be improved with a younger HLA-mismatched haploidentical donor (≤35 years) rather than an older matched related donor (≥35 years) or matched unrelated donor (≥35 years). We analyzed 406 consecutive allogenic HSCT recipients, with a median age of 54 years (range, 19 to 77), after a MRDT with a donor age of ≥35 years (n = 222), MUDT with a donor age of ≥35 years (n = 91), and HIDT with a donor age of ≤35 years (n = 93). Median follow-up time for survivors was 51.5 months. Compared with MRDT and MUDT, HIDT recipients had a similar median age at time of HSCT, hematopoietic cell transplant comorbidity index, disease risk index distribution, and donor recipient sex matching. The survival estimates and relapse incidence at 3 years post-HSCT were OS (64% for MRDT, 54% for MUDT, and 62% for HIDT), DFS (55% for MRDT, 44% for MUDT, and 58% for HIDT), Transplant related mortality (TRM) (19% for MRDT, 16% for MUDT, and 18% for HIDT), and relapse (26% for MRDT, 37% for MUDT, and 24% for HIDT). HIDT recipients had better 3-year relapse rates compared with MUDT recipients (24% versus 37%, P= .048), with similar DFS and OS in a univariate analysis. MRDT recipients had a better relapse rate (26% versus 37%, P = .042) compared with MUDT recipients. Recipients of HIDT also had significantly lower rates of moderate to severe chronic GVHD compared with MRDT and MUDT recipients (P = .01). Multivariable analysis showed no effect of donor on OS, DFS, relapse, and TRM. Recipients of HIDT from a young donor ≤35 years had similar OS, lower rates of chronic GVHD, and better chronic GVHD-free, relapse-free survival compared with patients undergoing transplantation with an MRD or a MUD donor ≥35 years. This study suggests that given a situation where a choice between a young haploidentical relative and an older matched unrelated donor is to be made, one can achieve similar survival with a haploidentical donor and significantly lower rates of chronic GVHD.
- Published
- 2019
50. Planned granulocyte-colony stimulating factor adversely impacts survival after allogeneic hematopoietic cell transplantation performed with Thymoglobulin for myeloid malignancy
- Author
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Miguel Angel Diaz, David Szwajcer, Lynette C.Y. Chee, Claudio G. Brunstein, Mary Eapen, Nina Orfali, David A. Rizzieri, Timothy Prestidge, Ian K. McNiece, Olle Ringdén, Melhem Solh, Pashna N. Munshi, Michael R. Grunwald, Sachiko Seo, Hillard M. Lazarus, Muhammad Bilal Abid, Mei-Jie Zhang, Filippo Milano, Jean A. Yared, Peiman Hematti, Jaap Jan Boelens, Mariam Allbee-Johnson, Marcie L. Riches, Scott D. Solomon, Andrew S. Artz, Jingmei Hsu, and Koen van Besien
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Oncology ,medicine.medical_specialty ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Adolescent ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Filgrastim ,Article ,hemic and lymphatic diseases ,Internal medicine ,Granulocyte Colony-Stimulating Factor ,medicine ,Immunology and Allergy ,Humans ,Transplantation, Homologous ,Antilymphocyte Serum ,Transplantation ,Thymoglobulin ,business.industry ,Hematopoietic Stem Cell Transplantation ,Cell Biology ,Hematology ,Middle Aged ,Donor Lymphocytes ,medicine.disease ,Anti-thymocyte globulin ,Granulocyte colony-stimulating factor ,Leukemia ,Leukemia, Myeloid, Acute ,surgical procedures, operative ,Molecular Medicine ,business ,medicine.drug - Abstract
The in vivo depletion of recipient and donor T lymphocytes using antithymocyte globulin (ATG; Thymoglobulin) is widely adopted in allogeneic hematopoietic stem cell transplantation (HCT) to reduce the incidence of both graft failure and graft-versus-host disease (GVHD). However, excess toxicity to donor lymphocytes may hamper immune reconstitution, compromising antitumor effects and increasing infection. Granulocyte-colony stimulating factor (G-CSF) administered early after HCT may increase ATG-mediated lymphotoxicity. This study aimed to investigate the effect of an interaction between ATG and post-transplantation granulocyte colony-stimulating factor (G-CSF) on allogeneic HCT outcomes, using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry. We studied patients age ≥18 years with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) who received Thymoglobulin-containing preparative regimens for HLA-matched sibling/unrelated or mismatched unrelated donor HCT between 2010 and 2018. The effect of planned G-CSF that was started between pretransplantation day 3 and post-transplantation day 12 was studied in comparison with transplantations that did not include G-CSF. Cox regression models were built to identify risk factors associated with outcomes at 1 year after transplantation. A total of 874 patients met the study eligibility criteria, of whom 459 (53%) received planned G-CSF. HCT with planned G-CSF was associated with a significantly increased risk for nonrelapse mortality (NRM) (hazard ratio [HR] 2.03; P.0001; 21% versus 12%) compared to HCT without G-CSF. The 6-month incidence of viral infection was higher with G-CSF (56% versus 47%; P = .007), with a particular increase in Epstein-Barr virus infections (19% versus 11%; P = .002). The observed higher NRM with planned G-CSF led to lower overall survival (HR, 1.52; P = .0005; 61% versus 72%). There was no difference in GVHD risk between the treatment groups. We performed 2 subgroup analyses showing that our findings held true in patients age ≥50 years and in centers where G-CSF was used in some, but not all, patients. In allogeneic peripheral blood HCT performed with Thymoglobulin for AML and MDS, G-CSF administered early post-transplantation resulted in a 2-fold increase in NRM and a 10% absolute decrement in survival. The use of planned G-CSF in the early post-transplantation period should be carefully considered on an individual patient basis, weighing any perceived benefits against these risks.
- Published
- 2021
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