106 results on '"Kitsada Wudhikarn"'
Search Results
2. P1238: GERMLINE HAVCR2 MUTATIONS AND THEIR RELATION TO THE CLINICAL SPECTRUM OF SUBCUTANEOUS PANNICULITIS-LIKE T-CELL LYMPHOMA AND HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS: RESULTS FROM A MULTICENTER STUDY
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Chantana Polprasert, Chatphatai Moonla, Patcharee Komvilaisak, Thanawat Rattanathammethee, Sunisa Kongkiatkamon, Kitsada Wudhikarn, Sirorat Kobbuaklee, Pitchayut Boonyabaramee, Samart Pakakasama, Piya Rujkijyanont, Chane Choed-Amphai, Kamon Phuakpet, Saranya Pongudom, Udomsak Bunworasate, Darintr Sosothikul, and Ponlapat Rojnuckarin
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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3. Genetic mutations associated with blood count abnormalities in myeloid neoplasms
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Chantana Polprasert, Sunisa Kongkiatkamon, Pimjai Niparuck, Thanawat Rattanathammethee, Kitsada Wudhikarn, Suporn Chuncharunee, Sirorat Kobbuaklee, Amornchai Suksusut, Theerin Lanamtieng, Panisinee Lawasut, Thiti Asawapanumas, Udomsak Bunworasate, and Ponlapat Rojnuckarin
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Myelodysplastic syndromes ,myelodysplastic syndromes/myeloproliferative neoplasms ,cytopenia ,gene mutation ,monocytosis ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Introduction Myelodysplastic syndromes (MDS) predominantly present with varying degrees of cytopenia, while myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) exhibit proliferative features. Genetic defects underlying different complete blood count (CBC) alterations remain to be defined.Objective We aimed to evaluate mutations and impacts on abnormal blood counts in MDS and MDS/MPN.Method MDS and MDS/MPN patients were recruited and sequenced by targeted next-generation sequencing. Clinical parameters, especially CBC, were evaluated for the association with genetic abnormalities and clinical outcomes.Results A total of 168 patients with myeloid neoplasms were recruited (92 cases of low-risk MDS, 57 cases of high-risk MDS and 19 cases of MDS/MPN). Compared to low-risk MDS and MDS/MPN, patients with high-risk MDS were presented with more severe neutropenia with 17.5% showing absolute neutrophil counts (ANC) lower than 0.5 × 109/L. Patients with MDS/MPN more commonly harboured mutations and had a higher number of mutations per case than low-risk MDS (94.7% vs. 56.5%; p
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- 2022
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4. Germline HAVCR2 mutations and their relation to the clinical spectrum of subcutaneous panniculitis-like T-cell lymphoma and hemophagocytic lymphohistiocytosis: results from a multicenter study and meta-analysis
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Chatphatai Moonla, Chantana Polprasert, Patcharee Komvilaisak, Thanawat Rattanathammethee, Sunisa Kongkiatkamon, Kitsada Wudhikarn, Sirorat Kobbuaklee, Pitchayut Boonyabaramee, Nuanrat Tangcheewinsirikul, Samart Pakakasama, Piya Rujkijyanont, Chane Choed-Amphai, Kamon Phuakpet, Saranya Pongudom, Udomsak Bunworasate, Narittee Sukswai, Darintr Sosothikul, and Ponlapat Rojnuckarin
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Germline HAVCR2 mutations are frequently detected in subcutaneous panniculitis-like T-cell lymphoma (SPTCL) patients with/without hemophagocytic lymphohistiocytosis (HLH) but factors associated with variable manifestations remain undetermined. To evaluate clinical variations and associated factors in SPTCL and/or HLH with/without HAVCR2 mutations, we performed direct sequencing of HAVCR2 exon 2 using DNA from patients with SPTCL or idiopathic HLH/HLH-like systemic illnesses, defined by HLH alone without secondary causes. The systematic review and individual patient data (IPD) level meta-analysis which included the present and previously published studies reporting HAVCR2 mutations in SPTCL with/without HLH populations was subsequently conducted using random-effects meta-analysis and multivariate logistic regression. Among 34 patients enrolled, ten of 28 SPTCL patients developed HLH/HLH-like systemic illnesses. Six cases with HAVCR2Y82C mutation manifested with HLH without panniculitis. Male sex (P=0.03) and age
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- 2023
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5. The impact of obesity and body weight on the outcome of patients with relapsed/refractory large B-cell lymphoma treated with axicabtagene ciloleucel
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Kitsada Wudhikarn, Radhika Bansal, Arushi Khurana, Matthew A. Hathcock, N. Nora Bennani, Jonas Paludo, Jose C. Villasboas, Yucai Wang, Patrick B. Johnston, Stephen M. Ansell, and Yi Lin
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2021
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6. The MAGIC algorithm probability is a validated response biomarker of treatment of acute graft-versus-host disease
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Hrishikesh K. Srinagesh, Umut Özbek, Urvi Kapoor, Francis Ayuk, Mina Aziz, Kaitlyn Ben-David, Hannah K. Choe, Zachariah DeFilipp, Aaron Etra, Stephan A. Grupp, Matthew J. Hartwell, Elizabeth O. Hexner, William J. Hogan, Alexander B. Karol, Stelios Kasikis, Carrie L. Kitko, Steven Kowalyk, Jung-Yi Lin, Hannah Major-Monfried, Stephan Mielke, Pietro Merli, George Morales, Rainer Ordemann, Michael A. Pulsipher, Muna Qayed, Pavan Reddy, Ran Reshef, Wolf Rösler, Karamjeet S. Sandhu, Tal Schechter, Jay Shah, Keith Sigel, Daniela Weber, Matthias Wölfl, Kitsada Wudhikarn, Rachel Young, John E. Levine, and James L.M. Ferrara
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Specialties of internal medicine ,RC581-951 - Abstract
Abstract: The Mount Sinai Acute GVHD International Consortium (MAGIC) algorithm probability (MAP), derived from 2 serum biomarkers, measures damage to crypts in the gastrointestinal tract during graft-versus-host disease (GVHD). We hypothesized that changes in MAP after treatment could validate it as a response biomarker. We prospectively collected serum samples and clinical stages of acute GVHD from 615 patients receiving hematopoietic cell transplantation in 20 centers at initiation of first-line systemic treatment and 4 weeks later. We computed MAPs and clinical responses and compared their abilities to predict 6-month nonrelapse mortality (NRM) in the validation cohort (n = 367). After 4 weeks of treatment, MAPs predicted NRM better than the change in clinical symptoms in all patients and identified 2 groups with significantly different NRM in both clinical responders (40% vs 12%, P < .0001) and nonresponders (65% vs 25%, P < .0001). MAPs successfully reclassified patients for NRM risk within every clinical grade of acute GVHD after 4 weeks of treatment. At the beginning of treatment, patients with a low MAP that rose above the threshold of 0.290 after 4 weeks of treatment had a significant increase in NRM, whereas patients with a high MAP at onset that fell below that threshold after treatment had a striking decrease in NRM that translated into clear differences in overall survival. We conclude that a MAP measured before and after treatment of acute GVHD is a response biomarker that predicts long-term outcomes more accurately than change in clinical symptoms. MAPs have the potential to guide therapy for acute GVHD and may function as a useful end point in clinical trials.
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- 2019
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7. Factors associated with erythropoiesis-stimulating agent hyporesponsiveness anemia in chronic kidney disease patients.
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Kamalas Amnuay, Nattachai Srisawat, Kitsada Wudhikarn, Dr, Thamathorn Assanasen, and Chantana Polprasert
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Anemia ,Chronic kidney disease ,Secondary hyperparathyroidism ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Anemia is one of the most common problems in chronic kidney disease (CKD). In several cases, despite comprehensive investigations, definite causes of anemia frequently remain unknown. We aimed to analyze the factors that possibly affect anemia in CKD patients who were referred for hematology consultation. A total of 87 patients were retrospectively included in the cohort. Forty-four cases were excluded, 30 cases with unavailable intact parathyroid hormone (iPTH) data, 11 cases with bone marrow diseases (8 Pure red cell aplasia, 3 Myelodysplastic syndrome) and 3 cases with thalassemia. Totally, 43 patients were analyzed. Patients with high iPTH had significantly lower Hemoglobin (Hb) level and required higher dose of erythropoietin stimulating agents (ESAs) compared with normal iPTH group (Hb 8.29 vs 9.24 mg/dL, p=0.032 and ESAs dose of 16,352.94 vs. 12,444.44 U/ week, p=0.024). In univariate followed by stepwise multivariate analysis, serum phosphate (PO4) was significantly associated with lower Hb level (p=0.01 and p=0.013, respectively). Hb level was inversely correlated with iPTH and PO4 level (r=-0.54, p
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- 2019
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8. Safety evaluation of axicabtagene ciloleucel for relapsed or refractory large B-cell lymphoma
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Karthik Nath, Kitsada Wudhikarn, Ana Alarcon Tomas, and Miguel-Angel Perales
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Pharmacology (medical) ,General Medicine - Published
- 2023
9. CNS Relapse in T-Cell Lymphoma Index: A Risk Score to Predict Central Nervous System Relapse in Patients with T-Cell Lymphomas
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Rahul S. Bhansali, Fredrik Ellin, Miao Cao, Thomas Relander, Wenrui Li, Qi Long, Nivetha Ganesan, Robert Stuver, Steven M. Horwitz, Kitsada Wudhikarn, Steven R Hwang, N. Nora Bennani, Julio C. Chavez, Lubomir Sokol, Hayder Saeed, Frank Duan, Pierluigi Porcu, Priyanka Pullarkat, Neha Mehta-Shah, Jasmine Zain, Miguel Ruiz, Jonathan E Brammer, Rishab Prakash, Swami P. Iyer, Adam J. Olszewski, Ajay Major, Sonali M. Smith, Peter A. Riedell, Caroline Goldin, Bradley M. Haverkos, Bei Hu, Pamela B. Allen, Wael Toama, Murali Janakiram, Taylor Brooks, Deepa Jagadeesh, Nisha Hariharan, Aaron M Goodman, Paola Ghione, Fatima Fayyaz, Joanna M. Rhodes, Elise A. Chong, James N. Gerson, Daniel J. Landsburg, Sunita Dwivedy Nasta, Stephen J. Schuster, Jakub Svoboda, Mats Jerkeman, and Stefan K. Barta
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
10. Outcomes of polatuzumab vedotin-containing regimens in real-world setting of relapsed and or refractory diffuse large B-cell lymphoma patients: a matched-control analysis from the Thai Lymphoma Study Group (TLSG)
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Thanawat Rattanathammethee, Lalita Norasetthada, Udomsak Bunworasate, Kitsada Wudhikarn, Jakrawadee Julamanee, Panarat Noiperm, Theerin Lanamtieng, Pisa Phiphitaporn, Manassamon Navinpipat, Piyapong Kanya, Dusit Jit-ueakul, Somchai Wongkhantee, Thanongsak Suwannathen, Juthatip Chaloemwong, Peerapon Wong, Nisa Makruasi, Archrob Khuhapinant, Kannadit Prayongratana, Pimjai Niparuck, Nonglak Kanitsap, Tawatchai Suwanban, and Tanin Intragumtornchai
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Hematology ,General Medicine - Published
- 2023
11. Improving cytokine-induced killer cell expansion using a gas-permeable culture method for clinical-scale production
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Supannikar, Tawinwung, Suparat, Tudsamran, Rattapoom, Thaiwong, Thiti, Asawapanumas, Kitsada, Wudhikarn, Chantiya, Chanswangphuwana, Nattiya, Hirankarn, Udomsak, Bunworasate, and Koramit, Suppipat
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Cytokine-induced killer (CIK) cells are a heterogeneous group of immune cells that exert potent MHC-unrestricted cytotoxicity toward various cancer cells in both solid and hematological malignancies.The purposes of this study were to compare the expansion and characteristics of cytokine-induced killer cells between a standard culture method and a gas-permeable culture method and to develop a clinical-scale expansion protocol for cytokine-induced killer cells using a gas-permeable culture method.We compared the absolute cell number, fold change, cell subsets, activation markers, cytokine concentrations, and cytotoxicity toward myeloid leukemia cell lines between cytokine-induced killer cells expanded using two different culture methods. Then, we determined the ability to achieve clinical-scale expansion of cytokine-induced killer cells using the gas-permeable culture method.Cytokine-induced killer cells in the gas-permeable culture method group exhibited significantly better expansion but maintained similar cell subsets, activation markers, and cytotoxicity to those in the standard culture method group. In addition, we successfully manufactured cytokine-induced killer cells for clinical use using the gas-permeable culture method. We also showed the clinical efficacy of allogeneic cytokine-induced killer cells produced by the gas-permeable culture method in a patient with acute myeloid leukemia that relapsed after allogeneic hematopoietic stem cell transplantation. This patient maintained ongoing disease remission for 2 years with minimal side effects after cytokine-induced killer cell infusion.We successfully developed a simple and effective protocol for the ex vivo expansion of cytokine-induced killer cells using the gas-permeable culture method for clinical application.
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- 2023
12. Expression of Programmed Cell Death-1 and Programmed Cell Death Ligands in Nodal Peripheral T-Cell Lymphoma: Expression Pattern and Potential Prognostic Relevance
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Thiti Asawapanumas, Nichthida Tangnantachai, Narittee Sukswai, Thammathorn Assanasen, Chantiya Chanswangphuwana, Panisinee Lawsut, Chantana Polprasert, Ponlapat Rojnuckarin, Udomsak Bunworasate, and Kitsada Wudhikarn
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Programmed Cell Death 1 Receptor ,Humans ,Lymphoma, T-Cell, Peripheral ,Apoptosis ,Hematology ,General Medicine ,Prognosis ,B7-H1 Antigen - Abstract
Programmed cell death (PD)/PD-ligands (PD-Ls) pathway plays an important role in the regulation of physiologic immune response. Several cancers, including lymphoma exhibit abnormal PD-1/PD-Ls expression, which may contribute to treatment failure, progression, and inferior outcomes. PD-1/PD-Ls expression has predominantly been described in B-cell lymphoma; such data in peripheral T-cell lymphoma (PTCL) is limited. We described PD-1/PD-Ls expression patterns and associations with clinical characteristics and outcomes, in patients with systemic PTCLs. Correlation between PD-1/PD-Ls expression and outcomes was analyzed in patients who received lymphoma-specific therapy. PD-1/PD-Ls expression was observed across all common PTCL histologies at different proportions (PD-1 0%–76.9%, PD-L1 38.5%–62.5%, and PD-L2 62.5%–100%) with PD-1 being highly expressed in angioimmunoblastic T-cell lymphoma. Baseline characteristics were comparable between PD-1/PD-Ls expression status. Of 47 patients who received lymphoma-specific therapy, outcomes were similar across all PD-L1/PD-L2 subgroups. In the Cox proportional hazard analysis, treatment response was the only factor associated with survival outcomes. However, PD-1/PD-Ls expression, either in lymphoma or stroma, was not a predictor for survival outcomes. In conclusion, differential PD-1/PD-Ls expressions were observed among various histological PTCL subtypes. In this study, we were unable to demonstrate an association between PD-1/PD-Ls expression, clinical characteristics, treatment response, and outcomes of PTCL patients.
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- 2022
13. Low toxicity and excellent outcomes in patients with DLBCL without residual lymphoma at the time of CD19 CAR T-cell therapy
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Kitsada Wudhikarn, Ana Alarcon Tomas, Jessica R. Flynn, Sean M. Devlin, Jamie Brower, Veronika Bachanova, Loretta J. Nastoupil, Joseph P McGuirk, Richard T Maziarz, Olalekan O. Oluwole, Stephen J. Schuster, David L. Porter, Michael R. Bishop, Peter A. Riedell, and Miguel-Angel Perales
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Hematology - Abstract
CD19 chimeric antigen receptor (CAR) T-cell therapy represents a breakthrough for patients with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) inducing sustained remissions in these patients. However, CAR T-cells can result in significant toxicities. Pre-infusion disease burden is associated with toxicities and outcomes after CAR T-cell therapy. We identified 33 patients with R/R DLBCL treated at 8 academic centers who had no detectable disease at the time of CAR T-cell therapy. The median time from leukapheresis to CAR T-cell infusion was 48 (19-193) days. Nine patients received axicabtagene ciloleucel and 24 received tisagenlecleucel. There was no severe (grade≥3) cytokine release syndrome and only 1 patient developed severe neurotoxicity (grade 4). After a median follow-up of 16 months, 13 patients relapsed (39.4%) and 6 died (18.1%). One-year event-free survival and overall survival were 59.6% and 81.3%, respectively. Our findings suggest that, in patients with R/R DLBCL who have an indication for CAR T-cell therapy, treating patients in complete remission at time of infusion is feasible, safe, and associated with favorable disease control. Further exploration in a larger clinical trial setting is warranted.
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- 2022
14. Interventions and outcomes of adult patients with B-ALL progressing after CD19 chimeric antigen receptor T-cell therapy
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Brigitte Senechal, Mark B. Geyer, Marco L. Davila, Kevin J. Curran, Mithat Gonen, Mikhail Roshal, Isabelle Riviere, Michel Sadelain, Peter Maslak, Jessica Flynn, Kitsada Wudhikarn, Claudia Diamonte, Renier J. Brentjens, Jae H. Park, Xiuyan Wang, and Elizabeth Halton
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Adult ,Male ,Oncology ,medicine.medical_specialty ,Clinical Trials and Observations ,Immunology ,Psychological intervention ,Immunotherapy, Adoptive ,Biochemistry ,Disease-Free Survival ,CD19 ,Refractory ,Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ,Internal medicine ,Antibodies, Bispecific ,medicine ,Humans ,Inotuzumab Ozogamicin ,Aged ,Salvage Therapy ,Response rate (survey) ,biology ,business.industry ,Cell Biology ,Hematology ,Middle Aged ,Chimeric antigen receptor ,Survival Rate ,Natural history ,biology.protein ,Female ,Chimeric Antigen Receptor T-Cell Therapy ,Blinatumomab ,business ,human activities ,medicine.drug - Abstract
CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has become a breakthrough treatment of patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, despite the high initial response rate, the majority of adult patients with B-ALL progress after CD19 CAR T-cell therapy. Data on the natural history, management, and outcome of adult B-ALL progressing after CD19 CAR T cells have not been described in detail. Herein, we report comprehensive data of 38 adult patients with B-ALL who progressed after CD19 CAR T therapy at our institution. The median time to progression after CAR T-cell therapy was 5.5 months. Median survival after post–CAR T progression was 7.5 months. A high disease burden at the time of CAR T-cell infusion was significantly associated with risk of post–CAR T progression. Thirty patients (79%) received salvage treatment of post–CAR T disease progression, and 13 patients (43%) achieved complete remission (CR), but remission duration was short. Notably, 7 (58.3%) of 12 patients achieved CR after blinatumomab and/or inotuzumab administered following post–CAR T failure. Multivariate analysis revealed that a longer remission duration from CAR T cells was associated with superior survival after progression following CAR T-cell therapy. In summary, overall prognosis of adult B-ALL patients progressing after CD19 CAR T cells was poor, although a subset of patients achieved sustained remissions to salvage treatments, including blinatumomab, inotuzumab, and reinfusion of CAR T cells. Novel therapeutic strategies are needed to reduce risk of progression after CAR T-cell therapy and improve outcomes of these patients.
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- 2021
15. Immune dysregulation in extranodal NK/T cell lymphomas: potential roles in pathogenesis and immunotherapy
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Chantana Polprasert, Ponlapat Rojnuckarin, and Kitsada Wudhikarn
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Pathogenesis ,medicine.anatomical_structure ,business.industry ,T cell ,medicine.medical_treatment ,Perspective ,Immunology ,medicine ,Hematology ,Immunotherapy ,Immune dysregulation ,medicine.disease_cause ,business - Published
- 2021
16. Epidemiology and Prognostic Index of Ocular Adnexal Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue (MALT) in Thailand: Results from the Thai Lymphoma Study Group (TLSG)
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Tanapun Thamgrang, Kannadit Prayongratana, Lalita Norasetthada, Thanawat Rattanathammethee, Arnuparp Lekhakula, Jakrawadee Julamanee, Udomsak Bunworasate, Kitsada Wudhikarn, Suporn Chuncharunee, Pimjai Niparuck, Somchai Wongkhantee, Noppadol Siritanaratanakul, Archrob Khuhapinant, Piyapong Kanya, Dusit Jit-Uaekul, Juthatip Chaloemwong, Nonglak Kanitsap, Nisa Makruasi, Kanchana Chansung, Chittima Sirijerachai, Tawatchai Suwanban, Peerapon Wong, and Tanin Intragumtornchai
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
17. Mucosal Associated Lymphoid Tissue Lymphoma in Thailand, a Nationwide Multicenter Registry and Prognostic Index; Results from the Thai Lymphoma Study Group (TLSG) Registry
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Kannadit Prayongratana, Tanapun Thamgrang, Lalita Norasetthada, Thanawat Rattanathammethee, Udomsak Bunworasate, Kitsada Wudhikarn, Arnuparp Lekhakula, Jakrawadee Julamanee, Suporn Chuncharunee, Pimjai Niparuck, Noppadol Siritanaratanakul, Archrob Khuhapinant, Piyapong Kanya, Kanchana Chansung, Chittima Sirijerachai, Dusit Jit-Uaekul, Juthatip Chaloemwong, Nonglak Kanitsap, Peerapon Wong, Nisa Makruasi, Somchai Wongkhantee, Tawatchai Suwanban, and Tanin Intragumtornchai
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
18. Inherited Germline DNA Repair Gene Defects Are Prevalent Among Thai Patients with Myeloid Neoplasms
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Sunisa Kongkiatkamon, Chupong Ittiwut, Thanawat Rattanathammethee, Wanna Chetruengchai, Kitsada Wudhikarn, Sirorat Kobbuaklee, Amornchai Suksusut, Pimjai Niparuck, Noppacharn Uaprasert, Suporn Chuncharunee, Udomsak Bunworasate, Kanya Suphapeetiporn, Ponlapat Rojnuckarin, and Chantana Polprasert
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
19. Infectious complications, immune reconstitution, and infection prophylaxis after CD19 chimeric antigen receptor T-cell therapy
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Kitsada Wudhikarn and Miguel-Angel Perales
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Transplantation ,Immune Reconstitution ,Receptors, Chimeric Antigen ,Hematologic Neoplasms ,Antigens, CD19 ,Cell- and Tissue-Based Therapy ,Humans ,Hematology ,Neoplasm Recurrence, Local ,Immunotherapy, Adoptive - Abstract
CD19-targeted chimeric antigen receptor (CAR) T-cell becomes a breakthrough therapy providing excellent remission rates and durable disease control for patients with relapsed/refractory (R/R) hematologic malignancies. However, CAR T-cells have several potential side effects including cytokine release syndrome, neurotoxicities, cytopenia, and hypogammaglobulinemia. Infection has been increasingly recognized as a complication of CAR T-cell therapy. Several factors predispose CAR T-cell recipients to infection. Fortunately, although studies show a high incidence of infection post-CAR T-cells, most infections are manageable. In contrast to patients who undergo hematopoietic stem cell transplant, less is known about post-CAR T-cell immune reconstitution. Therefore, evidence regarding antimicrobial prophylaxis and vaccination strategies in these patients is more limited. As CAR T-cell therapy becomes the standard treatment for R/R B lymphoid malignancies, we should expect a larger impact of infections in these patients and the need for increased clinical attention. Studies exploring infection and immune reconstitution after CAR T-cell therapy are clinically relevant and will provide us with a better understanding of the dynamics of immune function after CAR T-cell therapy including insights into appropriate strategies for prophylaxis and treatment of infections in these patients. In this review, we describe infections in recipients of CAR T-cells, and discuss risk factors and potential mitigation strategies.
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- 2022
20. Outcomes of Older Adults with Non-Hodgkin Lymphoma Undergoing Autologous Stem Cell Transplantation: A Mayo Clinic Cohort Analysis
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Kitsada Wudhikarn, Bradley M. Johnson, David J. Inwards, Luis F. Porrata, Ivana N. Micallef, Stephen M. Ansell, Willam J. Hogan, Jonas Paludo, Jose C. Villasboas, and Patrick B. Johnston
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Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Abstract
Autologous stem cell transplant (ASCT) is an important treatment that could offer a cure for lymphoma patients. However, advanced age is an important factor that determines eligibility and outcomes after ASCT. Over the past decade, attributed to improved supportive care, ASCT for older patients with increasing age has become more feasible.In this study, we report the single center outcomes of older patients with lymphoma undergoing ASCT at Mayo Clinic Rochester to highlight its interval improvement over time and help to redefine the implication of ASCT in the CAR T-cell era.A single center retrospective study describes characteristics and outcomes of older patients with lymphoma who underwent ASCT between 2000 and 2021. The study reports various relevant transplant related outcomes including progression free survival, overall survival, relapse incidence and non-relapse mortality (NRM) in older patients with various lymphoma histologic subtypes. The main outcome is focusing on NRM which is defined as time from ASCT to non-lymphoma related death with relapse being a competing event.of 492 patients aged ≥65 years old were analyzed. The median age at ASCT was 68.8 years. The most common indication for ASCT was diffuse large B cell lymphoma accounting for 59.3%. In multivariate analyses, patients undergoing ASCT in 2009-2021, performance status of zero and low Hematopoietic Cell Transplant Comorbidity Index (HCT-CI) (0-3) had a significantly lower NRM. Factors associated with OS included age, LDH, and HCT-CI.The 1- year NRM in older patients was low at 6.0% in concordance with previous reports. Age should not be the only factor determining patients' ASCT eligibility. With the proper patient selection, ASCT remains a reasonable option for older patients with lymphoma.
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- 2023
21. Prognostic factors and impact of CMV reactivation on acute myeloid leukemia patients after HLA-matched myeloablative allogeneic stem cell transplantation in a high CMV prevalence country
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Chantiya Chanswangphuwana, Kitsada Wudhikarn, Phandee Watanaboonyongcharoen, Patsita Kansuwan, Autcharaporn Sukperm, and Udomsak Bunworasate
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Immunology and Allergy ,Hematology - Abstract
Relapse of acute myeloid leukemia (AML) after allogeneic stem cell transplantation (allo-SCT) leads to dismal outcomes. This study aimed to identify high-risk patients and explore the effects of cytomegalovirus (CMV) reactivation in a high CMV-seropositive population.The study involved a single-center retrospective cohort in Thailand, analyzing clinical risk factors and CMV-mediated immune responses, correlated with transplant outcomes in AML patients.Eighty-five patients with AML in complete remission (CR) undergoing HLA-matched myeloablative allo-SCT between 2011 and February 2021 were enrolled. The relapse rate was 27.1% with the median time of 7 months after transplantation. The 3-year relapse-free-survival (RFS) and overall-survival (OS) were 72.2% and 80.8%, respectively. The disease status (CR1) and absence of chronic graft-versus-host disease (cGVHD) were independently significant adverse prognostic factors of RFS and OS. Ninety-two percent of recipient-donor pairs were both CMV seropositive. The CMV reactivation occurred in 54.1% of the patients. The clinically significant CMV infection rate was 49.4%. No CMV syndrome/disease or CMV-related mortality occurred. One-year cumulative incidence of relapse among CMV-reactivation and non-reactivation groups were 14.3% and 25.6%, respectively, without a statistically significant difference. Transplantation-related mortality was 11.1%.The transplantation beyond CR1 and absence of cGVHD are powerful prognostic factors associated with inferior RFS and OS. In a high CMV prevalence country, there appears to be no impact of CMV reactivation on relapse in AML patients undergoing an allo-SCT.
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- 2022
22. Chimeric antigen receptor T cells and management of toxicities: implications of biomarkers
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Kitsada Wudhikarn, Ana Alarcón Tomás, Kazunori Murata, and Miguel-Angel Perales
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- 2022
23. Principles of Checkpoint Inhibition in Malignant Lymphoma
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Kitsada Wudhikarn and Stephen M. Ansell
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- 2022
24. The influence of programmed cell death ligand 2 (PD-L2) expression on survival outcome and tumor microenvironment in diffuse large B cell lymphoma
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Narittee Sukswai, Thiti Asawapanumas, Chantiya Chanswangphuwana, San Krittikarux, Thamathorn Assanasen, Kitsada Wudhikarn, and Nichthida Tangnuntachai
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Cancer Research ,Programmed cell death ,Apoptosis ,Ligands ,B7-H1 Antigen ,Survival outcome ,03 medical and health sciences ,Lymphocytes, Tumor-Infiltrating ,0302 clinical medicine ,Expression pattern ,immune system diseases ,hemic and lymphatic diseases ,Programmed cell death 1 ,Biomarkers, Tumor ,Tumor Microenvironment ,medicine ,Humans ,Tumor microenvironment ,biology ,Chemistry ,Hematology ,Prognosis ,Ligand (biochemistry) ,medicine.disease ,Immune checkpoint ,Oncology ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Lymphoma, Large B-Cell, Diffuse ,Diffuse large B-cell lymphoma ,030215 immunology - Abstract
The frequency and significance of programmed cell death ligand (PD-L) 2 expression in diffuse large B cell lymphoma (DLBCL) remain undefined. We described the expression pattern of PD-L/PD-1 in 88 DLBCL patients using immunohistochemistry. The association between PD-L expression and clinical characteristics/outcomes were analyzed. PD-L1 and PD-L2 were expressed in 14.8% and 68.2% of DLBCL patients with median positivity on tumor cells of 100% and 90%, respectively. PD-1 on tumor-infiltrating lymphocytes (TILs) was expressed in 12.5% of patients. Interestingly, 45.5% of patients had PD-L2 expressing TILs which were significantly associated with bulky disease (
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- 2020
25. Infection during the first year in patients treated with CD19 CAR T cells for diffuse large B cell lymphoma
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Miguel-Angel Perales, Elena Mead, Sean M. Devlin, Aishat Afuye, Kitsada Wudhikarn, M. Lia Palomba, Michael Scordo, Martina Pennisi, Mari Lynne Silverberg, Marta Garcia-Recio, Molly Maloy, Connie L Batlevi, Gunjan L. Shah, Bianca Santomasso, Parastoo B. Dahi, Jessica Flynn, Craig S. Sauter, and Susan K. Seo
- Subjects
Adult ,Male ,T cell ,Antigens, CD19 ,Infections ,Immunotherapy, Adoptive ,lcsh:RC254-282 ,Article ,Hypogammaglobulinemia ,Young Adult ,Anti-Infective Agents ,Risk Factors ,Medicine ,Humans ,Cumulative incidence ,Risk factor ,B cell ,Aged ,Aged, 80 and over ,B-cell lymphoma ,business.industry ,Incidence ,Hematology ,Middle Aged ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Chimeric antigen receptor ,Cytokine release syndrome ,medicine.anatomical_structure ,Treatment Outcome ,Oncology ,Immunology ,Infectious diseases ,Female ,Lymphoma, Large B-Cell, Diffuse ,business ,Diffuse large B-cell lymphoma - Abstract
CD19-targeted chimeric antigen receptor (CAR) T cell therapy is an effective treatment for diffuse large B cell lymphoma (DLBCL). In addition to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS), B cell aplasia and hypogammaglobulinemia are common toxicities predisposing these patients to infections. We analyzed 60 patients with DLBCL treated with FDA-approved CD19 CAR T cells and report the incidence, risk factors, and management of infections during the first year after treatment. A total of 101 infectious events were observed, including 25 mild, 51 moderate, 23 severe, 1 life-threatening, and 1 fatal infection. Bacteria were the most common causative pathogens. The cumulative incidence of overall, bacterial, severe bacterial, viral, and fungal infection at 1 year were 63.3%, 57.2%, 29.6%, 44.7%, and 4%, respectively. In multivariate analyses, the use of systemic corticosteroids for the management of CRS or ICANS was associated with an increased risk of infections and prolonged admission. Impaired performance status and history of infections within 30 days before CAR T cell therapy was a risk factor for severe bacterial infection. In conclusion, infections were common within the first 60 days after CAR T cell therapy, however, they were not associated with an increased risk of death.
- Published
- 2020
26. DLBCL patients treated with CD19 CAR T cells experience a high burden of organ toxicities but low nonrelapse mortality
- Author
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Molly Maloy, Maria Lia Palomba, Marta Garcia-Recio, Martina Pennisi, Mari Lynne Silverberg, Connie L Batlevi, Gunjan L. Shah, Parastoo B. Dahi, Kitsada Wudhikarn, Bianca Santomasso, Craig S. Sauter, Miguel-Angel Perales, Elena Mead, Aishat Afuye, Sean M. Devlin, Jessica Flynn, and Michael Scordo
- Subjects
medicine.medical_specialty ,Performance status ,Clinical Trials and Observations ,business.industry ,T-Lymphocytes ,Incidence (epidemiology) ,Antigens, CD19 ,Receptors, Antigen, T-Cell ,Hematology ,medicine.disease ,Immunotherapy, Adoptive ,Gastroenterology ,Lymphoma ,Cytokine release syndrome ,Tolerability ,Internal medicine ,Toxicity ,Humans ,Medicine ,Cumulative incidence ,Lymphoma, Large B-Cell, Diffuse ,business ,Diffuse large B-cell lymphoma - Abstract
Cytokine release syndrome (CRS) immune effector cell–associated neurotoxicity syndrome are the most notable toxicities of CD19 chimeric antigen receptor (CAR) T-cell therapy. In addition, CAR T-cell–mediated toxicities can involve any organ system, with varied impacts on outcomes, depending on patient factors and involved organs. We performed detailed analysis of organ-specific toxicities and their association with outcomes in 60 patients with diffuse large B-cell lymphoma (DLBCL) treated with CD19 CAR T cells by assessing all toxicities in organ-based groups during the first year posttreatment. We observed 539 grade ≥2 and 289 grade ≥3 toxicities. Common grade ≥3 toxicities included hematological, metabolic, infectious, and neurological complications, with corresponding 1-year cumulative incidence of 57.7%, 54.8%, 35.4%, and 18.3%, respectively. Patients with impaired performance status had a higher risk of grade ≥3 metabolic complications, whereas elevated lactate dehydrogenase was associated with higher risks of grade ≥3 neurological and pulmonary toxicities. CRS was associated with higher incidence of grade ≥3 metabolic, pulmonary, and neurologic complications. The 1-year nonrelapse mortality and overall survival were 1.7% and 69%, respectively. Only grade ≥3 pulmonary toxicities were associated with an increased mortality risk. In summary, toxicity burdens after CD19 CAR T-cell therapy were high and varied by organ systems. Most toxicities were manageable and were rarely associated with mortality. Our study emphasizes the importance of toxicity assessment, which could serve as a benchmark for further research to reduce symptom burdens and improve tolerability in patients treated with CAR T cells.
- Published
- 2020
27. Disease risk and GVHD biomarkers can stratify patients for risk of relapse and nonrelapse mortality post hematopoietic cell transplant
- Author
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Steven Kowalyk, Mohammed S. Chaudhry, Elisabeth Schreiner, John E. Levine, Wolf Rösler, Rachel Young, Rainer Ordemann, Matthias Wölfl, Francis Ayuk, Jay Shah, Aaron Etra, Sarah Anand, Christina Dimopoulos, Matthew J. Hartwell, Elizabeth O. Hexner, Tal Schechter, Umut Ozbek, Yi-Bin Chen, Kitsada Wudhikarn, Carrie L. Kitko, Mina Aziz, Hannah K. Choe, James L.M. Ferrara, Pietro Merli, Michael A. Pulsipher, Ran Reshef, Stephanie Gergoudis, William J. Hogan, George Morales, Hrishikesh K. Srinagesh, Muna Qayed, Urvi Kapoor, Ryotaro Nakamura, Nicolaus Kröger, Gregory A. Yanik, and Allan Augustine
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Transplantation Conditioning ,medicine.medical_treatment ,Population ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Relapse prevention ,Article ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Risk factor ,education ,Survival rate ,education.field_of_study ,business.industry ,Hematopoietic Stem Cell Transplantation ,Immunosuppression ,Hematology ,Prognosis ,Survival Rate ,Transplantation ,surgical procedures, operative ,030104 developmental biology ,Hematologic Neoplasms ,030220 oncology & carcinogenesis ,Neoplasm Recurrence, Local ,Risk assessment ,business ,Algorithms ,Biomarkers ,Follow-Up Studies - Abstract
The graft-versus-leukemia (GVL) effect after allogeneic hematopoietic cell transplant (HCT) can prevent relapse but the risk of severe graft-vs-host disease (GVHD) leads to prolonged intensive immunosuppression and possible blunting of the GVL effect. Strategies to reduce immunosuppression in order to prevent relapse have been offset by increases in severe GVHD and non-relapse mortality (NRM). We recently validated the MAGIC algorithm probability (MAP) that predicts the risk for severe GVHD and NRM in asymptomatic patients using serum biomarkers. In this study we tested whether the MAP could identify patients whose risk for relapse is higher than their risk for severe GVHD and NRM. The multicenter study population (n=1604) was divided into two cohorts: historical (2006–2015, n=702) and current (2015–2017, n=902) with similar non-relapse mortality, relapse, and survival. On day 28 post-HCT, patients who had not developed GVHD (75% of the population) and who possessed a low MAP were at much higher risk for relapse (24%) than severe GVHD and NRM (16% and 9%); this difference was even more pronounced in patients with a high disease risk index (relapse 33%, NRM 9%). Such patients are good candidates to test relapse prevention strategies that might enhance GVL.
- Published
- 2020
28. Prediction of Response to Erythropoiesis Stimulating Agents in Low-Risk Myelodysplastic Syndromes
- Author
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Saroj Hattakitpanitchakul, Sirorat Kobbuaklee, Kitsada Wudhikarn, and Chantana Polprasert
- Subjects
Aged, 80 and over ,Chromosome Aberrations ,Male ,Anemia ,General Medicine ,Prognosis ,Isocitrate Dehydrogenase ,Dioxygenases ,DNA-Binding Proteins ,Repressor Proteins ,Survival Rate ,Asian People ,Predictive Value of Tests ,Myelodysplastic Syndromes ,Mutation ,Hematinics ,Humans ,Blood Transfusion ,Female ,Erythropoietin ,Aged ,Retrospective Studies - Abstract
Erythropoiesis stimulating agents (ESAs) represents the principal treatments for anemia in patients with lower-risk myelodysplastic syndromes (MDS). Pre-treatment erythropoietin (EPO) level and previous blood transfusion requirement are the two major predictors for response to ESAs. However, most evidence was derived from Western countries whereas there have been limited data in patients with Asian background.We retrospectively collected data on patients with low-risk MDS who received ESAs. Erythroid response was evaluated according to IWG 2006 criteria. MDS subtypes, r-IPSS, baseline hemoglobin (Hb), ESAs dosage and erythropoietin level were reviewed from medical records. Gene mutations were analyzed in patients' blood or bone marrow at diagnosis by 40-gene myeloid panel targeted sequencing. Clinical and laboratory parameters were compared between erythroid responder and non-responder groups.A total of 47 patients were recruited in the study. The median age at diagnosis of the patients in this cohort was 77 years (IQR, 70-83) and 44.7% were male. The median revised international prognostic scoring system (R-IPSS) score of patients was 2.5. Response rate to ESAs was 46.8% (22/47). Median EPO level in responders was significantly lower than non-responders (27.7 vs. 59.1 U/L, p=0.02). Median ESAs dosage in responder group was 30,000 units per week. Cytogenetic abnormalities were detected in 27.3% and 24% of the responder and non-responder groups, respectively. Of 22 patients with available 40 gene mutation targeted sequencing, ASXL1, IDH2 and TET2 represented the 3 most common mutations and were found in 22%, 22% and 17%, respectively. There were no differences in cytogenetic abnormalities and gene mutations between groups. Patients who responded to ESAs showed a higher 5-year overall survival (OS) compared to non-responders (5-year OS 75% vs. 60.9%; p=0.008).We conclude that a low serum EPO level is a predictive factor for responsiveness to ESAs in Asian patients with low-risk MDS.
- Published
- 2021
29. Outcomes of relapsed B-cell acute lymphoblastic leukemia after sequential treatment with blinatumomab and inotuzumab
- Author
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Kitsada Wudhikarn, Amber C. King, Mark B. Geyer, Mikhail Roshal, Yvette Bernal, Boglarka Gyurkocza, Miguel-Angel Perales, and Jae H. Park
- Subjects
Adult ,Lymphoma, B-Cell ,Recurrence ,Antibodies, Bispecific ,Antigens, CD19 ,Humans ,Inotuzumab Ozogamicin ,Hematology ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Burkitt Lymphoma - Abstract
Novel monoclonal antibody (mAb)-based therapies targeting CD19 and CD22 (blinatumomab and inotuzumab) have shown high rates of complete remission (CR) and been used as a bridging treatment to potentially curative allogeneic hematopoietic stem cell transplantation (alloHSCT) in adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). However, limited data exist on the outcome of patients resistant to both mAbs as well as responses to each agent when progressed after the alternate antigen-targeted mAb. Herein, we report outcomes of 29 patients with R/R B-ALL previously treated with both blinatumomab and inotuzumab. Twenty-five patients (86.2%) received blinatumomab as first mAb (mAb1), and CD19-negative/dim relapses were observed in 44% of the patients. Inotuzumab induced CR in 68% of the patients for post-blinatumomab relapse regardless of CD19 expression status. The median time between mAb1 and mAb2 was 99 days. Twelve (63.2%) of 19 patients who achieved remission after mAb2 underwent alloHSCT. The median time from mAb2 to alloHSCT was 37.5 days. Acute graft-versus-host disease and nonrelapse mortality were observed in 58.3% (grade 3 or higher, 25%) and 41.7%, respectively. With a median follow-up of 16.8 months after mAb2, 19 patients (65.5%) relapsed, and 21 patients (72.4%) have died. Overall survival was not different between alloHSCT and non-alloHSCT patients. In conclusion, patients with B-ALL who relapsed after blinatumomab could be successfully rescued by inotuzumab as a bridge to alloHSCT but represent an ultra-high-risk group with poor overall survival. Further studies, including novel consolidation and treatment sequence, may improve outcomes of these patients.
- Published
- 2021
30. Spectrum of hematological malignancies, clonal evolution and outcomes in 144 Mayo Clinic patients with germline predisposition syndromes
- Author
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Terra L. Lasho, Abhishek A. Mangaonkar, Shakila P. Khan, Kitsada Wudhikarn, William J. Hogan, Jennifer L. Oliveira, Dong Chen, Ayalew Tefferi, Ronald S. Go, Naseema Gangat, Rhett P. Ketterling, Alejandro Ferrer, Mira A. Kohorst, Ann M. Moyer, David S. Viswanatha, Emma C. St. Martin, Mrinal M. Patnaik, Rong He, Horatiu Olteanu, Avni Y. Joshi, Aref Al-Kali, and Phuong L. Nguyen
- Subjects
Adult ,Male ,medicine.medical_specialty ,Ataxia ,Myeloid ,Adolescent ,Anemia ,Genetic counseling ,Lymphoproliferative disorders ,Somatic evolution in cancer ,Clonal Evolution ,Young Adult ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Congenital Bone Marrow Failure Syndromes ,Humans ,Genetic Predisposition to Disease ,Fertility preservation ,Child ,Germ-Line Mutation ,Aged ,Anemia, Diamond-Blackfan ,business.industry ,Infant ,Hematology ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,Fanconi Anemia ,Child, Preschool ,Hematologic Neoplasms ,Hematological neoplasm ,Female ,medicine.symptom ,business - Abstract
Germline predisposition syndromes (GPS) result from constitutional aberrations in tumor suppressive and homeostatic genes, increasing risk for neoplasia in affected kindred. In this study, we present clinical and genomic data on 144 Mayo Clinic patients with GPS; 59 evaluated prospectively using an algorithm-based diagnostic approach in the setting of a dedicated GPS/ inherited bone marrow failure syndrome (IBMFS) clinic. Seventy-two (50%) patients had IBMFS (telomere biology disorders-32,Fanconi anemia-18, Diamon Blackfan Anemia - 11, congenital neutropenia-5, Schwachman-Diamond Syndrome-5 and Bloom Syndrome-1), 27 (19%) had GPS with antecedent thrombocytopenia (RUNX1-FPD-15, ANKRD26-6, ETV6-2, GATA1-1, MPL-3), 28 (19%) had GPS without antecedent thrombocytopenia (GATA2 haploinsufficiency-16, DDX41-10, CBL-1 and CEBPA-1) and 17 (12%) had general cancer predisposition syndromes (ataxia telangiectasia-7, heterozygous ATM variants-3, CHEK2-2, TP53-2, CDK2NA-1, NF1-1 and Nijmegen Breakage Syndrome-1). Homozygous and heterozygous ATM pathogenic variants were exclusively associated with lymphoproliferative disorders (LPD), while DDX41 GPS was associated with LPD and myeloid neoplasms. The use of somatic NGS-testing identified clonal evolution in GPS patients, with ASXL1, RAS pathway genes, SRSF2 and TET2 being most frequently mutated. Fifty-two (91%) of 59 prospectively identified GPS patients had a change in their management approach, including additional GPS-related screening in 42 (71%), referral for allogenic HSCT workup and screening of related donors in 16 (27%), medication initiation and selection of specific conditioning regimens in 14 (24%), and genetic counseling with specific intent of fertility preservation and preconceptual counselling in 10 (17%) patients; highlighting the importance of dedicated GPS screening, detection and management programs for patients with hematological neoplasms. This article is protected by copyright. All rights reserved.
- Published
- 2021
31. Age defining immune effector cell associated neurotoxicity syndromes in aggressive large B cell lymphoma patients treated with axicabtagene ciloleucel
- Author
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Jose C. Villasboas, Yi Lin, N. Nora Bennani, Stephen M. Ansell, Matthew A. Hathcock, Yucai Wang, Jonas Paludo, Radhika Bansal, Sherri A. Braksick, Patrick B. Johnston, Arushi Khurana, and Kitsada Wudhikarn
- Subjects
Adult ,Neurotoxicity Syndrome ,Biological Products ,business.industry ,Age Factors ,Hematology ,Middle Aged ,medicine.disease ,Immunotherapy, Adoptive ,Antineoplastic Agents, Immunological ,Immunology ,Immune effector cell ,Aphasia ,Medicine ,Humans ,Neurotoxicity Syndromes ,Lymphoma, Large B-Cell, Diffuse ,business ,B-cell lymphoma ,Confusion ,Agraphia ,Aged ,Retrospective Studies - Published
- 2021
32. How to Sequence Therapies in Peripheral T Cell Lymphoma
- Author
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N. Nora Bennani and Kitsada Wudhikarn
- Subjects
Oncology ,medicine.medical_specialty ,Chemotherapy ,business.industry ,medicine.medical_treatment ,Lymphoproliferative disorders ,medicine.disease ,Peripheral T-cell lymphoma ,Autologous stem-cell transplantation ,Refractory ,Internal medicine ,Induction therapy ,medicine ,T-cell lymphoma ,Pharmacology (medical) ,business ,Anaplastic large-cell lymphoma - Abstract
Peripheral T cell lymphoma (PTCL) represents a heterogeneous group of rare lymphoproliferative disorders. Historically, there has been a lack of pathobiological understanding of PTCL. With the exception of ALK-positive anaplastic large cell lymphoma, patients with PTCL have less favorable outcomes, with most patients relapsing shortly after conventional anthracycline-containing multi-agent chemotherapy. The standard management approach for PTCL involves induction therapy followed by autologous stem cell transplantation. Patients with relapsed/refractory PTCL have dismal outcomes and limited treatment options despite the available novel agents, therefore remaining a critical unmet need. By virtue of advancement in cancer biology over the recent years, the treatment landscape of PTCL has gradually evolved from conventional chemotherapy based on solely morphological diagnosis toward more individualized therapies by integrating molecular attributes of PTCL to the traditional treatment paradigm. We are at the edge of witnessing a paradigm shift in PTCL management.
- Published
- 2021
33. The impact of obesity and body weight on the outcome of patients with relapsed/refractory large B-cell lymphoma treated with axicabtagene ciloleucel
- Author
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Radhika Bansal, N. Nora Bennani, Kitsada Wudhikarn, Matthew A. Hathcock, Jose C. Villasboas, Stephen M. Ansell, Yucai Wang, Patrick B. Johnston, Arushi Khurana, Yi Lin, and Jonas Paludo
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,MEDLINE ,Body weight ,Immunotherapy, Adoptive ,Antineoplastic Agents, Immunological ,Text mining ,Internal medicine ,Correspondence ,medicine ,Humans ,Obesity ,B-cell lymphoma ,RC254-282 ,Aged ,Biological Products ,business.industry ,Body Weight ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Hematology ,Immunotherapy ,Middle Aged ,medicine.disease ,Treatment Outcome ,Relapsed refractory ,Female ,Lymphoma, Large B-Cell, Diffuse ,Neoplasm Recurrence, Local ,business - Published
- 2021
34. How to Sequence Therapies in Peripheral T Cell Lymphoma
- Author
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Kitsada, Wudhikarn and N Nora, Bennani
- Subjects
Clinical Decision-Making ,Decision Trees ,Disease Management ,Lymphoma, T-Cell, Peripheral ,Prognosis ,Combined Modality Therapy ,Treatment Outcome ,Drug Resistance, Neoplasm ,Recurrence ,Retreatment ,Biomarkers, Tumor ,Humans ,Disease Susceptibility ,Neoplasm Grading ,Precision Medicine ,Algorithms ,Neoplasm Staging - Abstract
Peripheral T cell lymphoma (PTCL) represents a heterogeneous group of rare lymphoproliferative disorders. Historically, there has been a lack of pathobiological understanding of PTCL. With the exception of ALK-positive anaplastic large cell lymphoma, patients with PTCL have less favorable outcomes, with most patients relapsing shortly after conventional anthracycline-containing multi-agent chemotherapy. The standard management approach for PTCL involves induction therapy followed by autologous stem cell transplantation. Patients with relapsed/refractory PTCL have dismal outcomes and limited treatment options despite the available novel agents, therefore remaining a critical unmet need. By virtue of advancement in cancer biology over the recent years, the treatment landscape of PTCL has gradually evolved from conventional chemotherapy based on solely morphological diagnosis toward more individualized therapies by integrating molecular attributes of PTCL to the traditional treatment paradigm. We are at the edge of witnessing a paradigm shift in PTCL management.
- Published
- 2021
35. Clinical features and survival outcomes in patients with chronic myelomonocytic leukemia arising in the context of germline predisposition syndromes
- Author
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Naseema Gangat, Alejandro Ferrer, Kitsada Wudhikarn, Jessica K. Altman, Ayalew Tefferi, Mrinal M. Patnaik, Terra L. Lasho, Emma C. St. Martin, Abhishek A. Mangaonkar, William J. Hogan, and Lucy A. Godley
- Subjects
Male ,business.industry ,MEDLINE ,Chronic myelomonocytic leukemia ,Context (language use) ,Leukemia, Myelomonocytic, Chronic ,Hematology ,Middle Aged ,medicine.disease ,Bioinformatics ,Survival Analysis ,Germline ,Text mining ,Germ Cells ,medicine ,Humans ,In patient ,Female ,Genetic Predisposition to Disease ,business ,Germ-Line Mutation ,Aged - Published
- 2021
36. Programmed Cell Death 1 and Programmed Cell Death Ligands in Extranodal Natural Killer/T Cell Lymphoma: Expression Pattern and Potential Prognostic Relevance
- Author
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Hamidah Muhamad, Thamatorn Assanasen, Narittee Suksawai, Chantana Polprasert, Kitsada Wudhikarn, and Udomsak Bunworasate
- Subjects
Adult ,Male ,Herpesvirus 4, Human ,Programmed cell death ,Stromal cell ,Programmed Cell Death 1 Receptor ,Antineoplastic Agents ,B7-H1 Antigen ,03 medical and health sciences ,0302 clinical medicine ,Stroma ,Biomarkers, Tumor ,medicine ,Humans ,T-cell lymphoma ,Proportional Hazards Models ,business.industry ,Hematology ,General Medicine ,Middle Aged ,Prognosis ,Programmed Cell Death 1 Ligand 2 Protein ,medicine.disease ,Natural killer T cell ,Progression-Free Survival ,Immune checkpoint ,Lymphoma ,Blockade ,Lymphoma, Extranodal NK-T-Cell ,Survival Rate ,Treatment Outcome ,030220 oncology & carcinogenesis ,DNA, Viral ,Cancer research ,Female ,business ,030215 immunology - Abstract
The programmed cell death 1/programmed cell death ligands (PD-1/PD-Ls) axis is a potential immune escape mechanism of cancers. However, data on the PD-1/PD-Ls pathway in EBV-associated extranodal natural killer/T cell lymphoma (ENKTL) and its clinical implication are limited. Herein, we characterized PD-1/PD-L expression and its prognosis relevance in 49 ENKTL patients in Thailand. PD-L1 was expressed frequently on both lymphoma cells (61.2%) and stroma (77.5%), whereas PD-L2 expression was more common on lymphoma (63.2%) than stromal cells. PD-1 was positive in 20.5% of stroma, but undetectable on lymphoma cells. There was no association between baseline clinical characteristics and the expression PD-1/PD-Ls. The survival of patients with PD-Ls on tumor cells was poor. For PD-L1-positive versus negative cases, the 2-year event-free survival (EFS) was 42.2 versus 71.8% (p = 0.03) and 2-year overall survival (OS) was 45.4 versus 78.9% (p = 0.02), respectively. Comparing between patients with PD-L2-positive and PD-L2-negative lymphoma, the 2-year EFS was 37.1 versus 82.4% (p = 0.02) and 2-year OS was 45.2 versus 82.4% (p = 0.03), respectively. Neither PD-1 nor PD-Ls expression in the stroma predicted outcomes. In conclusion, PD-Ls were frequently expressed on ENKTL cells and associated with inferior outcomes. Therefore, PD-Ls are potential prognostic biomarkers and the roles of immune checkpoint blockade therapy in ENKTL deserve further investigation.
- Published
- 2019
37. Clinical correlates and prognostic impact of clonal hematopoiesis in multiple myeloma patients receiving post-autologous stem cell transplantation lenalidomide maintenance therapy
- Author
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Betsy LaPlant, A. Keith Stewart, Angela Dispenzieri, Mrinal M. Patnaik, Chang Xin Shi, Abhishek A. Mangaonkar, Morie A. Gertz, S. Vincent Rajkumar, Terra L. Lasho, Martha Q. Lacy, Wilson I. Gonsalves, Leslie Padrnos, Kitsada Wudhikarn, Rhett P. Ketterling, Shaji Kumar, and Rafael Fonseca
- Subjects
Oncology ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,Transplantation, Autologous ,Maintenance Chemotherapy ,Autologous stem-cell transplantation ,Text mining ,Maintenance therapy ,Internal medicine ,medicine ,Humans ,Immunologic Factors ,Lenalidomide ,Melphalan ,Multiple myeloma ,Aged ,Retrospective Studies ,Salvage Therapy ,Venous Thrombosis ,business.industry ,Clonal hematopoiesis ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,medicine.disease ,Prognosis ,Female ,Clonal Hematopoiesis ,business ,Multiple Myeloma ,medicine.drug - Published
- 2021
38. Future of CAR T cells in multiple myeloma
- Author
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Eric L. Smith, Kitsada Wudhikarn, and Sham Mailankody
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Disease ,Immunotherapy, Adoptive ,03 medical and health sciences ,Immunotherapy in Multiple Myeloma ,0302 clinical medicine ,Antigen ,Refractory ,Recurrence ,Internal medicine ,medicine ,Humans ,Treatment Failure ,Multiple myeloma ,Aged ,Receptors, Chimeric Antigen ,business.industry ,Hematology ,Immunotherapy ,medicine.disease ,Chimeric antigen receptor ,Clinical trial ,030104 developmental biology ,030220 oncology & carcinogenesis ,Female ,Car t cells ,business ,Multiple Myeloma - Abstract
Despite the significant improvement in survival outcomes of multiple myeloma (MM) over the past decade, it remains an incurable disease. Patients with triple-class refractory MM have limited treatment options and a dismal prognosis. Chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen has transformed the treatment armamentarium of relapsed/refractory MM (RRMM), with unprecedented overall response rates in this difficult-to-treat patient population. However, a significant proportion of patients ultimately relapse despite achieving deep remission. Several innovative approaches, including alternative/dual-antigen–specific CAR T-cell constructs, genetically engineered “off-the-shelf” CAR T cells, and strategies to counteract an immunosuppressive microenvironment, may dramatically reshape the field of CAR T-cell therapy in the future. These strategies are being actively investigated in preclinical and early clinical trial settings with the hopes of enhancing the durability of responses and, thereby, improving the overall survival of RRMM patients after CAR T-cell therapy.
- Published
- 2020
39. Isolated Extramedullary Relapse After Human Leukocyte Antigen-Matched Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia Patients: Case Reports and Literature Review
- Author
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Photsawee Khemaphiphat, Kitsada Wudhikarn, Udomsak Bunworasate, and Chantiya Chanswangphuwana
- Subjects
Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Central nervous system ,Human leukocyte antigen ,Hematopoietic stem cell transplantation ,Disease ,HLA Antigens ,Recurrence ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Transplantation ,business.industry ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Leukemia, Myeloid, Acute ,surgical procedures, operative ,medicine.anatomical_structure ,Surgery ,Lymph ,Bone marrow ,business ,Chemoradiotherapy - Abstract
Isolated extramedullary relapse (iEMR) of acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is rare and has a dismal prognosis. Among 67 patients with AML after allo-HSCT, iEMR and bone marrow relapse occurred in 6% and 20.9%, respectively, with a median time to relapse of 11.5 and 6.5 months, respectively. Here, we presented 4 iEMR-AML cases. Common relapse locations occurred in the central nervous system, skin, and lymph nodes. We also report a rare case of cardiac iEMR that responded to chemoradiotherapy. Two cases responded to local/systemic treatments, which resulted in prolonged survival. Another case had iEMR in the presence of chronic graft-versus-host disease. Bone marrow relapse occurring after iEMR was typical and found in three-fourths of the cases. In conclusion, iEMR-AML occurrence after allo-HSCT is not rare in Thai patients. Its unpredictability and lack of graft-versus-leukemia effect highlight the importance of monitoring EMR carefully and promptly providing treatments once it is detected.
- Published
- 2020
40. Frequent mutations in HLA and related genes in extranodal NK/T cell lymphomas
- Author
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Yasuhide Takeuchi, Nobuyuki Kakiuchi, Seishi Ogawa, Hideki Makishima, Kenichi Chiba, Satoru Miyano, Kenichi Yoshida, Wimonmas Sitthi, Panisinee Lawasut, Hiroko Tanaka, Sunisa Kongkiatkamon, Yuichi Shiraishi, Thamathorn Assanasen, Koji Izutsu, Hamidah Muhamad, Chantana Polprasert, Ponlapat Rojnuckarin, Kitsada Wudhikarn, Nichthida Tangnuntachai, and Udomsak Bunworasate
- Subjects
Cancer Research ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Somatic cell ,T cell ,Hematology ,Human leukocyte antigen ,Biology ,medicine.disease_cause ,Epstein–Barr virus ,Immunohistochemistry ,Lymphoma, Extranodal NK-T-Cell ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Oncology ,hemic and lymphatic diseases ,030220 oncology & carcinogenesis ,Immunology ,Mutation ,medicine ,Humans ,Gene ,030215 immunology - Abstract
Extranodal NK/T cell lymphomas (ENKTCLs) are aggressive Epstein-Barr virus-associated T/NK neoplasms that predominantly affect Asians. To explore the causative somatic events, we conducted a comprehensive genetic analysis of 19 ENKTCL patients by whole-genome (
- Published
- 2020
41. The International Prognostic Index Is Associated with Outcomes in Diffuse Large B Cell Lymphoma after Chimeric Antigen Receptor T Cell Therapy
- Author
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Elizabeth Halton, Michael Scordo, Aishat Afuye, M. Lia Palomba, Craig S. Sauter, Gunjan L. Shah, Sergio Giralt, Jessica Flynn, Parastoo B. Dahi, Martina Pennisi, Sean M. Devlin, Mari Lynne Silverberg, Bianca Santomasso, Kitsada Wudhikarn, Rosalia Alonso-Trillo, Miguel-Angel Perales, Elena Mead, Connie W. Batlevi, Molly Maloy, Josel D. Ruiz, Marta Garcia-Recio, and Roni Shouval
- Subjects
Oncology ,medicine.medical_specialty ,Cell- and Tissue-Based Therapy ,Immunotherapy, Adoptive ,CD19 ,Article ,Cell therapy ,International Prognostic Index ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Immunology and Allergy ,Humans ,Transplantation ,Receptors, Chimeric Antigen ,biology ,business.industry ,Cell Biology ,Hematology ,medicine.disease ,Prognosis ,Chimeric antigen receptor ,Cytokine release syndrome ,biology.protein ,Molecular Medicine ,Chimeric Antigen Receptor T-Cell Therapy ,Lymphoma, Large B-Cell, Diffuse ,business ,Diffuse large B-cell lymphoma - Abstract
CD19-targeted chimeric antigen receptor (CAR) T cells have shown excellent activity against relapsed and refractory (R/R) diffuse large B cell lymphoma (DLBCL). CAR T cell therapy is associated with early toxicities, including cytokine release syndrome and neurotoxicity. The incidence and severity of these toxicities has been associated in part with baseline disease and patient characteristics, which also may impact overall survival (OS) and progression-free survival (PFS). However, there are limited data on patient selection and how to better predict toxicities or outcomes. Indexes used in patients with DLBCL, such as the International Prognostic Index (IPI and age-adjusted IPI [aaIPI]) and in transplantation recipients, such as the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), have not been evaluated in this setting. Here we evaluated 4 indices— IPI, aaIPI, HCT-CI, and the Charlson Comorbidity Index (CCI)—and their associations with early CAR T cell related-toxicities and outcomes. We demonstrated an association between high-risk IPI or aaIPI and inferior PFS in patients with R/R DLBCL treated with CAR T cell therapy. We also found an association between aaIPI and IPI with OS and neurotoxicity, respectively. CCI was not associated with toxicities or outcomes, and owing to the small sample size, we could not draw a conclusion regarding associations with the HCT-CI. Both the IPI and aaIPI are widely used tools that can now provide better information to guide selection of patients who would best benefit from CD19 CAR T cell therapy.
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- 2020
42. Dissecting factors influencing response to CAR T cell therapy in B lymphoid hematologic malignancies: from basic to practice
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Jae H. Park and Kitsada Wudhikarn
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Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Cell ,Antigens, CD19 ,Receptors, Antigen, T-Cell ,Immunotherapy, Adoptive ,03 medical and health sciences ,Therapeutic approach ,0302 clinical medicine ,Internal medicine ,Medicine ,Humans ,Predictive biomarker ,Receptors, Chimeric Antigen ,business.industry ,Hematology ,Immunotherapy ,medicine.disease ,Chimeric antigen receptor ,Lymphoma ,Leukemia ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Hematologic Neoplasms ,CAR T-cell therapy ,Neoplasm Recurrence, Local ,business ,030215 immunology - Abstract
Over the past recent years, CD19-targeted chimeric antigen receptor T (CAR T) cell has transformed the treatment of relapsed/refractory (R/R) B lymphoid hematologic malignancy. CAR T cell therapy elicits an excellent anti-tumor effect and extends long-term disease-free remission in these difficult-to-treat patients. Notwithstanding, despite the impressive anti-tumor efficacy, some patients fail to attain clinical response or relapse after extended follow-up. The success of CAR T cell therapy involves complex interplays between host, tumor, and CAR T cell-associated arrays. Researchers have extensively explored potential predictive biomarkers for response to CAR T cell therapy. Ability to identify clinical and biological factors associated with improved response will help determine appropriate patients for CAR T cell treatment and enhance the clinical outcome of this novel therapeutic approach.
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- 2020
43. The MAGIC algorithm probability is a validated response biomarker of treatment of acute graft-versus-host disease
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Mina Aziz, Tal Schechter, Steven Kowalyk, Pietro Merli, Hannah K. Choe, Wolf Rösler, Muna Qayed, Aaron Etra, George Morales, Jung-Yi Lin, Rainer Ordemann, Hannah Major-Monfried, Keith Sigel, Matthias Wölfl, John E. Levine, Karamjeet S. Sandhu, Michael A. Pulsipher, Umut Ozbek, Alexander B. Karol, Stephan Mielke, William J. Hogan, Ran Reshef, Francis Ayuk, James L.M. Ferrara, Elizabeth O. Hexner, Daniela Weber, Stelios Kasikis, Rachel Young, Jay Shah, Carrie L. Kitko, Kitsada Wudhikarn, Kaitlyn Ben-David, Hrishikesh K. Srinagesh, Zachariah DeFilipp, Matthew J. Hartwell, Stephan A. Grupp, Urvi Kapoor, and Pavan Reddy
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Transplantation ,business.industry ,Graft vs Host Disease ,Hematology ,Disease ,Serum samples ,Clinical trial ,Serum biomarkers ,Acute graft versus host disease ,Acute Disease ,Medicine ,Biomarker (medicine) ,Humans ,Nonrelapse mortality ,business ,Algorithm ,Algorithms ,Biomarkers ,Probability - Abstract
The Mount Sinai Acute GVHD International Consortium (MAGIC) algorithm probability (MAP), derived from 2 serum biomarkers, measures damage to crypts in the gastrointestinal tract during graft-versus-host disease (GVHD). We hypothesized that changes in MAP after treatment could validate it as a response biomarker. We prospectively collected serum samples and clinical stages of acute GVHD from 615 patients receiving hematopoietic cell transplantation in 20 centers at initiation of first-line systemic treatment and 4 weeks later. We computed MAPs and clinical responses and compared their abilities to predict 6-month nonrelapse mortality (NRM) in the validation cohort (n = 367). After 4 weeks of treatment, MAPs predicted NRM better than the change in clinical symptoms in all patients and identified 2 groups with significantly different NRM in both clinical responders (40% vs 12%, P < .0001) and nonresponders (65% vs 25%, P < .0001). MAPs successfully reclassified patients for NRM risk within every clinical grade of acute GVHD after 4 weeks of treatment. At the beginning of treatment, patients with a low MAP that rose above the threshold of 0.290 after 4 weeks of treatment had a significant increase in NRM, whereas patients with a high MAP at onset that fell below that threshold after treatment had a striking decrease in NRM that translated into clear differences in overall survival. We conclude that a MAP measured before and after treatment of acute GVHD is a response biomarker that predicts long-term outcomes more accurately than change in clinical symptoms. MAPs have the potential to guide therapy for acute GVHD and may function as a useful end point in clinical trials.
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- 2019
44. Monoclonal antibodies in multiple myeloma: Current and emerging targets and mechanisms of action
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Kitsada Wudhikarn, Beatriz Wills, and Alexander M. Lesokhin
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Antibody-drug conjugate ,Immunoconjugates ,Neoplasm, Residual ,medicine.drug_class ,Clinical Biochemistry ,Disease ,Monoclonal antibody ,Antibodies, Monoclonal, Humanized ,Drug Administration Schedule ,Article ,Bortezomib ,03 medical and health sciences ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,Recurrence ,Antibodies, Bispecific ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Humans ,Elotuzumab ,Lenalidomide ,Multiple myeloma ,Clinical Trials as Topic ,biology ,business.industry ,Daratumumab ,Antibodies, Monoclonal ,medicine.disease ,Survival Analysis ,Thalidomide ,Biopharmaceutical ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Antibody ,business ,Multiple Myeloma ,030215 immunology ,medicine.drug - Abstract
The recent development of monoclonal antibodies (mAbs) has revolutionized the treatment armamentarium for multiple myeloma. The success of daratumumab and elotuzumab in relapsed/refractory patients, has generated tremendous enthusiasm for mAbs in this disease. Combination treatment with other anti-myeloma treatment modalities and clinical evaluation in newly diagnosed patients are expected to fundamentally change the natural history of the disease. Advances in biopharmaceutical engineering together with a robust interest in novel mAb-derivatives, including antibody drug conjugates and poly-specific antibodies are the next rapidly approaching treatment frontier in multiple myeloma. In this review, we comprehensively outline the currently available evidence and the future landscape of mAbs and mAb-derivative therapies in multiple myeloma.
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- 2019
45. MAGIC biomarkers predict long-term outcomes for steroid-resistant acute GVHD
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Anne S. Renteria, Michael A. Pulsipher, James L.M. Ferrara, Ivan J. Torres, Aaron Etra, Andrew C. Harris, Ernst Holler, Nicolaus Kröger, Mohammed S. Chaudhry, Wolf Rösler, George Morales, Rainer Ordemann, Yvonne A. Efebera, Muna Qayed, John E. Levine, Elizabeth O. Hexner, Yi-Bin Chen, Hannah Major-Monfried, Umut Ozbek, Pavan Reddy, William J. Hogan, Steven Kowalyk, Attaphol Pawarode, Kitsada Wudhikarn, Francis Ayuk, Mina Aziz, Ryotaro Nakamura, Carrie L. Kitko, Rachel Young, Matthias Wölfl, Jay Shah, Ran Reshef, Gregory A. Yanik, Daniela Weber, and Matthew J. Hartwell
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Adult ,Oncology ,medicine.medical_specialty ,Multivariate analysis ,Adolescent ,medicine.medical_treatment ,Immunology ,Drug Resistance ,Graft vs Host Disease ,Pancreatitis-Associated Proteins ,Biochemistry ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Adrenal Cortex Hormones ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Child ,Aged ,Transplantation ,Receiver operating characteristic ,business.industry ,Hematopoietic Stem Cell Transplantation ,Area under the curve ,Infant ,Immunosuppression ,Cell Biology ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Interleukin-1 Receptor-Like 1 Protein ,Treatment Outcome ,Graft-versus-host disease ,Child, Preschool ,030220 oncology & carcinogenesis ,Cohort ,Biomarker (medicine) ,business ,Biomarkers ,030215 immunology - Abstract
Acute graft-versus-host disease (GVHD) is treated with systemic corticosteroid immunosuppression. Clinical response after 1 week of therapy often guides further treatment decisions, but long-term outcomes vary widely among centers, and more accurate predictive tests are urgently needed. We analyzed clinical data and blood samples taken 1 week after systemic treatment of GVHD from 507 patients from 17 centers of the Mount Sinai Acute GVHD International Consortium (MAGIC), dividing them into a test cohort (n = 236) and 2 validation cohorts separated in time (n = 142 and n = 129). Initial response to systemic steroids correlated with response at 4 weeks, 1-year nonrelapse mortality (NRM), and overall survival (OS). A previously validated algorithm of 2 MAGIC biomarkers (ST2 and REG3α) consistently separated steroid-resistant patients into 2 groups with dramatically different NRM and OS (P < .001 for all 3 cohorts). High biomarker probability, resistance to steroids, and GVHD severity (Minnesota risk) were all significant predictors of NRM in multivariate analysis. A direct comparison of receiver operating characteristic curves showed that the area under the curve for biomarker probability (0.82) was significantly greater than that for steroid response (0.68, P = .004) and for Minnesota risk (0.72, P = .005). In conclusion, MAGIC biomarker probabilities generated after 1 week of systemic treatment of GVHD predict long-term outcomes in steroid-resistant GVHD better than clinical criteria and should prove useful in developing better treatment strategies.
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- 2018
46. Improvement in Outcomes of Autologous Stem Cell Transplant in Patients with Lymphoma Older Than 70 Years: The Significance of Age in 2020s?
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Kitsada Wudhikarn, Ivana N. Micallef, Luis F. Porrata, Jose C. Villasboas, Stephen M. Ansell, Jonas Paludo, Bradley K. Johnson, Patrick B. Johnston, and David J. Inwards
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Oncology ,medicine.medical_specialty ,business.industry ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Lymphoma ,Internal medicine ,medicine ,In patient ,Stem cell ,business - Abstract
Backgrounds: Autologous stem cell transplant (ASCT) has been the standard treatment approach for patients with relapsed or high-risk lymphoma for several decades. Despite the improvement in supportive care, age has remained one of the critical factors that determines transplant eligibility and outcomes. Herein, we explored the transplant-related outcomes of patients with lymphoma aged 70 years or older at our institution and compared to those with younger ages. Methods: In this retrospective single center study, we include all patients with diagnosis of lymphoma who underwent ASCT between January 2000 and February 2021 at Mayo Clinic, Rochester, Minnesota. In addition to data obtained from the transplant database, we abstracted data from electronic medical record. We described relevant clinical characteristics and transplant associated outcomes including engraftment, transplant related mortality, relapse incidence, and survival outcomes. We compared the key transplant related outcomes with patients at the younger age group between 65 and 70 years old. Results: A total of 196 patients with lymphoma aged 70 years or older underwent ASCT between January 2000 and February 2021. The median age of patients at the time of ASCT was 72.4 (70.0-78.7) years with 24 patients (12.2%) being older than 75 years old. Of 196 patients, 76 (38.8%) had Charlson comorbidity index of 3 or higher and 10 (5.1%) had performance status of 2 or higher at the time of ASCT. Table 1 summarizes the relevant baseline clinical characteristics of 196 patients in this cohort including the comparison with younger patients (age 65-70 years old, n=296). The most common transplant indication in this cohort was relapsed diffuse large B cell lymphoma. The majority of patients (91.3%) received peripheral blood graft with a median CD34+ cell dose of 5.14x10 6 cells/kg which was significantly lower than younger patients (P=0.01). The rate of neutrophil and platelet engraftment was 99.0% and 98.8% with corresponding median time to engraftment of 13 days for both cell lineages. The 30- and 100-day non-relapse mortality (NRM) of the entire cohort was 1.5% (95%CI 0-3.2%) and 4.6% (95%CI 1.6-7.5%) not statistically different between 70-75 years old and 75 years or older cohorts. With the median follow-up duration of 48 months, the 2-year event free survival (EFS) and overall survival (OS) was 55.9% (95%CI 49.2-63.5%) and 67.4% (95%CI 61.0-74.5%), respectively. Patients from the 70 years old or older cohort had similar EFS but inferior OS compared to the 65-70 years old cohort. However, there was no difference in EFS and OS between 70-75 and >75 years old cohorts. There was overall an improved trend of 30-day NRM, 2-year EFS and 2-year OS over the 3 different transplant periods (Figures). Although not statistically significant, patients who underwent ASCT between 2000 and 2006 had a trend towards higher 30-day NRM compared to patients who were transplanted at later time points (7.3% vs 0%, P=0.06). The major causes of death included progressive lymphoma, infection, and conditioning regimen related organ toxicities. Conclusion: Outcomes of ASCT in older patients with lymphoma have improved over time with an excellent 30-day NRM (0%) in the past recent years. The major cause of treatment failure after ASCT was progressive disease. With appropriate patient selection, ASCT in older patients is feasible and provides acceptable outcomes comparable to the patients from younger age group. Figure 1 Figure 1. Disclosures Paludo: Karyopharm: Research Funding. Ansell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding.
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- 2021
47. A Multi-Institutional Retrospective Analysis of T-Cell Lymphomas with Central Nervous System Relapse
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Nivetha Ganesan, Kitsada Wudhikarn, Adam J. Olszewski, Daniel J. Landsburg, James N. Gerson, Steven M. Horwitz, Neha Mehta-Shah, Robert N. Stuver, Priyanka Pullarkat, Brad Haverkos, Julio C. Chavez, Rahul S. Bhansali, Stephen J. Schuster, Steven R. Hwang, Swami P. Iyer, Pamela B. Allen, Caroline Goldin, Hayder Saeed, Lubomir Sokol, Sunita D. Nasta, Elise A. Chong, Jakub Svoboda, Rishab Prakash, Stefan K. Barta, and Nora N Bennani
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Oncology ,medicine.medical_specialty ,business.industry ,T cell ,Immunology ,Central nervous system ,Cell Biology ,Hematology ,Biochemistry ,medicine.anatomical_structure ,Internal medicine ,Retrospective analysis ,Medicine ,business - Abstract
Introduction Central nervous system (CNS) relapse (CNSr) in patients with aggressive non-Hodgkin lymphoma (NHL) occurs uncommonly (estimated incidence 5%) but carries a high morbidity and mortality. Studies have identified risk factors for CNSr such as high tumor burden and extranodal (EN) disease. However, most focus on B-cell NHL with minimal data in T-cell lymphomas (TCL), which are significantly less common and more heterogenous. The few small series of CNSr in TCL report a median overall survival (OS) less than 3 months (mo) with incidence ranging from 2.6-9%. To better define CNSr in TCL, we performed a multi-institutional retrospective analysis of TCL patients with CNSr and herein describe clinicopathologic characteristics and treatment of CNSr. Methods We performed a retrospective observational study using data from 9 US academic centers with IRB approval at individual sites. We included adult patients diagnosed with a mature T-cell neoplasm as per the 2016 WHO classification between 1/1/2009-1/1/2019, who were found to have CNSr at any time after initial diagnosis, and collected patient, disease, and treatment characteristics at time of initial diagnosis as well as at CNSr. Patients with a diagnosis of a precursor T-cell malignancy or with CNS disease identified at initial TCL diagnosis (TCLd) and/or prior to first-line systemic treatment were excluded. Results In this analysis, we report the outcomes of 75 patients (male n=45, female n=30). At TCLd, the median age was 59 years (range 20-81), and 61% of patients (n=46) had an IPI score of at least 3, 92% (n=69) had EN involvement with 37% (n=28) involving at least 2 EN sites, and 59% (n=44) had BM involvement. The most common pathologic diagnoses were peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS; 24%, n=18), angioimmunoblastic T-cell lymphoma (AITL; 17%, n=13), adult T-cell leukemia/lymphoma (ATLL; 17%, n=13), and mycosis fungoides (MF; 12%, n=9) (Figure 1A). First-line systemic therapy for TCL included anthracyclines for 72% (n=54). Autologous and allogenic transplants were performed prior to CNSr in 12% (n=9) and 8% (n=6) of patients, respectively. Prior to CNSr, 48% (n=36) had non-CNS relapse. Some form of CNS prophylaxis was used during initial systemic lymphoma therapy in 24% of patients (n=18), predominantly intrathecal methotrexate (IT MTX; n=16). Median time from TCLd to CNSr was 8.5mo, though this was significantly longer in MF (46.8mo [range 17.5-187.7]) versus PTCL, NOS (7.6mo [range 1.1-58.4], P=0.0002), AITL (21.2mo [range 2.0-61.6, P=0.008), and ATLL (7.3mo [range 0.7-46.4], P=0.0005) (Figure 1B). CNSr developed within 6mo of TCLd in 31% of patients (n=23) and within 12mo in 57% (n=43). Symptoms related to CNSr occurred in 71% of patients (n=53). CNSr patterns were 61% leptomeningeal (n=46), 21% parenchymal (n=16), and 17% both (n=13) with no significant survival difference between leptomeningeal or parenchymal disease alone (HR 1.45, 95% CI 0.78-2.70, P=0.28). Concomitant systemic relapse was observed in 59% of patients (n=44). The most common CNS-directed therapy for CNSr was IT MTX (56%; n=42), though multiple different IT and/or systemic regimens were used. Patients received a median of 1 line of CNS-directed treatment (range 0-5). The overall response rate to initial CNS directed treatment was 32% (16% CR, 16% PR). Median follow up after CNSr was 40.7mo. At last follow up, 83% had died (n=62). Median OS after CNSr was 4.6mo (range 0.1-68.7) (Figure 1C). Those with ATLL had the shortest median OS after CNSr (2.7mo) versus 6.3mo in MF (HR 3.69, 95% CI 1.44-9.42, P=0.005), 6.5mo in AITL (HR 2.16, 95% CI 0.92-5.06, P=0.054), and 4.8mo in PTCL, NOS (HR 1.49, 95% CI 0.70-3.19, P=0.27) (Figure 1D). The most common cause of death was progressive lymphoma (77%; n=48). Conclusions This is to our knowledge the largest series of CNSr in TCL to date. Most CNSr occurred within 12mo, though CNSr occurred later in patients with MF. Although the prognosis after CNSr was generally poor, we found that median OS in CNSr was longer than previously reported, perhaps reflecting more effective treatments for CNS and systemic relapse, inclusion of MF, or lead time bias. Further analysis of the impact of different treatment strategies and outcomes in CNSr was limited by the small sample size and heterogeneity within our cohort, and future analyses in a larger cohort should focus on factors associated with outcomes. Figure 1 Figure 1. Disclosures Horwitz: ADC Therapeutics, Affimed, Aileron, Celgene, Daiichi Sankyo, Forty Seven, Inc., Kyowa Hakko Kirin, Millennium /Takeda, Seattle Genetics, Trillium Therapeutics, and Verastem/SecuraBio.: Consultancy, Research Funding; Affimed: Research Funding; Aileron: Research Funding; Acrotech Biopharma, Affimed, ADC Therapeutics, Astex, Merck, Portola Pharma, C4 Therapeutics, Celgene, Janssen, Kura Oncology, Kyowa Hakko Kirin, Myeloid Therapeutics, ONO Pharmaceuticals, Seattle Genetics, Shoreline Biosciences, Inc, Takeda, Trillium Th: Consultancy; Celgene: Research Funding; C4 Therapeutics: Consultancy; Crispr Therapeutics: Research Funding; Daiichi Sankyo: Research Funding; Forty Seven, Inc.: Research Funding; Kura Oncology: Consultancy; Kyowa Hakko Kirin: Consultancy, Research Funding; Millennium/Takeda: Research Funding; Myeloid Therapeutics: Consultancy; ONO Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy, Research Funding; Secura Bio: Consultancy; Shoreline Biosciences, Inc.: Consultancy; Takeda: Consultancy; Trillium Therapeutics: Consultancy, Research Funding; Tubulis: Consultancy; Verastem/Securabio: Research Funding. Bennani: Purdue Pharma: Other: Advisory Board; Daichii Sankyo Inc: Other: Advisory Board; Kyowa Kirin: Other: Advisory Board; Vividion: Other: Advisory Board; Kymera: Other: Advisory Board; Verastem: Other: Advisory Board. Chavez: AstraZeneca: Research Funding; ADC Therapeutics: Consultancy, Research Funding; Merk: Research Funding; MorphoSys, AstraZeneca, BeiGene, Genentech, Kite, a Gilead Company, and Epizyme: Speakers Bureau; MorphoSys, Bayer, Karyopharm, Kite, a Gilead Company, Novartis, Janssen, AbbVie, TeneoBio, and Pfizer: Consultancy; BMS: Speakers Bureau. Sokol: Dren Bio: Membership on an entity's Board of Directors or advisory committees; Kyowa-Kirin: Membership on an entity's Board of Directors or advisory committees. Saeed: Nektar Therapeutics: Consultancy, Other: research investigator; MEI Pharma Inc: Consultancy, Other: investigator; Celgene Corporation: Consultancy, Other: investigator; MorphoSys AG: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb Company: Consultancy; sano-aventis U.S.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceutica Products, LP: Consultancy, Other: investigator; Kite Pharma: Consultancy, Other: investigator; Other-TG therapeutics: Consultancy, Other: investigator; Other-Epizyme, Inc.: Consultancy; Other-Secura Bio, Inc.: Consultancy; Seattle Genetics, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees. Mehta-Shah: Kiowa Hakko Kirin: Consultancy; C4 Therapeutics: Consultancy; Verastem: Research Funding; Karyopharm: Consultancy; Ono Pharmaceuticals: Consultancy; Secura Bio: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; AstraZeneca: Research Funding; Bristol Myers Squibb: Research Funding; Celgene: Research Funding; Innate Pharmaceuticals: Research Funding; Roche/Genentech: Research Funding; Corvus Pharmaceuticals: Research Funding. Olszewski: TG Therapeutics: Research Funding; PrecisionBio: Research Funding; Celldex Therapeutics: Research Funding; Acrotech Pharma: Research Funding; Genentech, Inc.: Research Funding; Genmab: Research Funding. Allen: Epizyme: Consultancy; MorphoSys: Consultancy; ADC Therapeutics: Consultancy; Secure Bio: Consultancy; Kyowa Kirin: Consultancy. Gerson: Abbvie: Consultancy; Kite: Consultancy; TG Therapeutics: Consultancy; Pharmacyclics: Consultancy. Landsburg: Triphase: Research Funding; Takeda: Research Funding; Curis: Research Funding; ADCT: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Other: DSMB member; Incyte: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees. Schuster: Adaptive Biotechnologies: Research Funding; Pharmacyclics: Research Funding; Merck: Research Funding; Genentech/Roche: Consultancy, Research Funding; Tessa Theraputics: Consultancy; Juno Theraputics: Consultancy, Research Funding; Loxo Oncology: Consultancy; BeiGene: Consultancy; Alimera Sciences: Consultancy; Acerta Pharma/AstraZeneca: Consultancy; Abbvie: Consultancy, Research Funding; Nordic Nanovector: Consultancy; Novartis: Consultancy, Honoraria, Patents & Royalties, Research Funding; Incyte: Research Funding; TG Theraputics: Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Svoboda: Atara: Consultancy; Adaptive: Consultancy, Research Funding; Astra Zeneca: Consultancy, Research Funding; Imbrium: Consultancy; Pharmacyclics: Consultancy, Research Funding; Genmab: Consultancy; Merck: Research Funding; Incyte: Research Funding; BMS: Consultancy, Research Funding; TG: Research Funding; Seattle Genetics: Consultancy, Research Funding. Barta: Kyowa Kirin: Honoraria; Acrotech: Honoraria; Daiichi Sankyo: Honoraria; Seagen: Honoraria.
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- 2021
48. Outcomes of Aggressive B Cell Lymphoma Patients with No Evidence of Measurable Disease at the Time of CD19 Chimeric Antigen Receptor T Cell Therapy: The Experience from the CAR T Cell Consortium
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Kitsada Wudhikarn, Veronika Bachanova, David L. Porter, Miguel-Angel Perales, Jamie Brower, Joseph P. McGuirk, Ana Alarcon Tomas, Peter A. Riedell, Loretta J. Nastoupil, and Richard T. Maziarz
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biology ,business.industry ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,CD19 ,Measurable Disease ,medicine ,Cancer research ,biology.protein ,Chimeric Antigen Receptor T-Cell Therapy ,Car t cells ,B-cell lymphoma ,business ,health care economics and organizations - Abstract
Introduction: CD19 chimeric antigen receptor (CAR) T cells provide high response rates and durable disease remission for many patients with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). Pre-treatment disease burden has been identified as a potential determining factor for efficacy and toxicity of CAR T cells, with lower tumor burden being associated with improved survival and lower toxicity (Bishop et al. Blood Advances 2019, Dean et al. Blood Advances 2020). However, in-vivo expansion and persistence of CAR T cells are thought to be influenced by pre-treatment tumor burden and play a role in treatment outcomes. Here, we report the characteristics, outcomes and toxicity patterns of DLBCL patients with no measurable diseases at the time of commercial CD19 CAR T cell therapy. Methods: The CAR T cell Consortium includes 8 US academic institutions that have collected data on adult patients with R/R DLBCL who received axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) between April 2018 and October 2019. This multicenter retrospective study included all patients with no evidence of disease as evaluated by PET/CT scan and other indicated investigations before CAR T cell infusion. Baseline demographic data, CAR T cell treatment characteristics, response to CAR T cell therapy, outcomes and adverse events were analyzed and reported. Cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) were reviewed and re-graded using the American Society of Transplant Cellular Therapy Consensus Criteria (Lee et al. BBMT 2019). Results: A total of 236 patients with DLBCL had CD19 CAR T cell therapy during the study period (151 axi-cel, and 85 tisa-cel). Data on disease status before CAR T cell infusion was available in 199 patients. Of these 199 patients, 15 (7.5%) were in complete remission (CR), as per investigator assessment at the time of CAR T-cell infusion (4 received axi-cel and 11 received tisa-cel). The median age was 61.6 years (range, 38.1-75.5). The indications of CAR T cell treatments included 12 R/R de novo DLBCL, 2 high grade B cell lymphoma and 1 transformed DLBCL. The median time from leukapheresis to CAR T cell infusion was 48 days (range, 19-89). After leukapheresis, 13 patients (86.7%) received bridging therapy prior to CAR T cell infusion. Of the 13 patients who received bridging therapy, all had repeated PET/CT scan prior to CAR T cell infusion showing no evidence of measurable diseases. The median time from pre-infusion PET/CT scan to the day of CAR T infusion was 14 days (range, 6-77) with 7 and 8 patients having CAR T cells in the inpatient and outpatient settings, respectively. Baseline characteristics and details of CAR T cell therapy are summarized in the Table. CRS was observed in 3 patients (20.0%) (2 Grade 1, 1 Grade 2) with the median time to onset of 1 day (range, 0-5). Of the 3 patients who developed CRS, 1 received axi-cel and 2 received tisa-cel. Tocilizumab was provided in 1 patient and no patients developed ICANS. At day +100 after CAR T cell infusion, 12 of 15 patients remained in CR (3 patients relapsed at day +30, +64 and +88). The 100-day treatment related mortality was 0%. At a median follow-up duration of 20 months, 10 patients remained alive and progression free, while 5 patients relapsed (4 DLBCL, 1 HGBL) and 4 patients died (3 from progressive disease and 1 from non-relapse mortality). The 1-year event free survival and overall survival was 66.0% (95%CI 45.7-59.4%) and 73.3% (95%CI 54.0-99.5%), respectively (Figure). The 1-year cumulative incidence of relapse was 27.3% (95%CI 3.4-51.3%). Conclusion: Patients with DLBCL who had no residual disease at the time of commercial CD19 CAR T cell infusion had excellent outcomes with very low incidence of CAR T cell-associated complications. These patients may be managed and followed safely in the ambulatory setting. Our findings emphasize the importance of pre-treatment disease burden on efficacy and tolerability of CAR T cell therapy. Our findings suggest that patients in CR at the time of infusion may still benefit from CAR T cell therapies and could serve as an initiative to explore the role of CAR T cells as a consolidation for patients with high risk DLBCL achieving CR after conventional treatments in the prospective clinical trial setting. Figure 1 Figure 1. Disclosures Bachanova: KaryoPharma: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; FATE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gamida Cell: Membership on an entity's Board of Directors or advisory committees, Research Funding. Maziarz: Artiva Therapeutics: Consultancy; CRISPR Therapeutics: Consultancy; Intellia: Honoraria; Omeros: Research Funding; Allovir: Consultancy, Research Funding; Bristol-Myers, Squibb/Celgene,, Intellia, Kite: Honoraria; Athersys: Other: Data and Safety Monitoring Board, Patents & Royalties; Novartis: Consultancy, Other: Data and Safety Monitoring board, Research Funding; Incyte Corporation: Consultancy, Honoraria; Vor Pharma: Other: Data and Safety Monitoring Board. McGuirk: Novartis: Research Funding; Fresenius Biotech: Research Funding; Novartis: Research Funding; Pluristem Therapeutics: Research Funding; EcoR1 Capital: Consultancy; Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Allovir: Consultancy, Honoraria, Research Funding; Bellicum Pharmaceuticals: Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Astelllas Pharma: Research Funding; Gamida Cell: Research Funding. Nastoupil: Epizyme: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Caribou Biosciences: Research Funding; Janssen: Honoraria, Research Funding; Gilead/Kite: Honoraria, Research Funding; Genentech: Honoraria, Research Funding; Denovo Pharma: Other: DSMC; Bayer: Honoraria; TG Therapeutics: Honoraria, Research Funding; MorphoSys: Honoraria; Bristol Myers Squibb/Celgene: Honoraria, Research Funding; Takeda: Honoraria, Other: DSMC, Research Funding; ADC Therapeutics: Honoraria; IGM Biosciences: Research Funding; Pfizer: Honoraria, Research Funding. Porter: Janssen: Membership on an entity's Board of Directors or advisory committees; National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees; Unity: Patents & Royalties; Kite/Gilead: Membership on an entity's Board of Directors or advisory committees; American Society for Transplantation and Cellular Therapy: Honoraria; ASH: Membership on an entity's Board of Directors or advisory committees; Wiley and Sons Publishing: Honoraria; Novartis: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees; DeCart: Membership on an entity's Board of Directors or advisory committees; GenenTech: Current Employment, Current equity holder in publicly-traded company. Riedell: Kite/Gilead: Research Funding, Speakers Bureau; MorphoSys: Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Consultancy; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Calibr: Research Funding; Xencor: Research Funding; Tessa Therapeutics: Research Funding. Perales: Cidara: Honoraria; Novartis: Honoraria, Other; Merck: Honoraria; Incyte: Honoraria, Other; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; Sellas Life Sciences: Honoraria; NexImmune: Honoraria; Karyopharm: Honoraria; Servier: Honoraria; Takeda: Honoraria; Equilium: Honoraria; Omeros: Honoraria; Kite/Gilead: Honoraria, Other; MorphoSys: Honoraria; Miltenyi Biotec: Honoraria, Other; Nektar Therapeutics: Honoraria, Other; Medigene: Honoraria.
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- 2021
49. Characteristics, outcomes, and risk factors of ICANS after axicabtagene ciloleucel: Does age matter?
- Author
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Arushi Khurana, Jonas Paludo, Matthew A. Hathcock, Yucai Wang, Radhika Bansal, Michael W. Ruff, Sherri A. Braksick, Stephen M. Ansell, Jose C. Villasboas, Yi Lin, Patrick B. Johnston, N. Nora Bennani, Kitsada Wudhikarn, and Ivan D. Carabenciov
- Subjects
Cancer Research ,Neurotoxicity Syndrome ,biology ,business.industry ,medicine.disease ,CD19 ,Cytokine release syndrome ,Oncology ,Immunology ,medicine ,biology.protein ,Immune effector cell ,Chimeric Antigen Receptor T-Cell Therapy ,business - Abstract
e19556 Background: CD19 chimeric antigen receptor T cell therapy possesses unique side effects including cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS). Age is a major risk factor for ICANS. However, whether ICANS in older patients is different compared to younger patients is unknown. Herein, we report clinical course, outcomes and risk factors for ICANS in older patients with large B cell lymphoma (LBCL) treated with axicabtagene ciloleucel (axi-cel). Methods: We comprehensively reviewed detailed clinical courses of ICANS in 78 adult patients with LBCL treated with axi-cel between June 2016 and October 2020. Incidence, manifestation, risk factors, treatment, and outcomes of ICANS were compared between patients age ≥60 (n=32) and
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- 2021
50. The impact of body weight and body mass index on outcomes of diffuse large B-cell lymphoma treated with axicabtagene ciloleucel
- Author
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Yi Lin, Jose C. Villasboas, Jonas Paludo, N. Nora Bennani, Matthew A. Hathcock, Yucai Wang, Radhika Bansal, Kitsada Wudhikarn, Arushi Khurana, Stephen M. Ansell, and Patrick B. Johnston
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Retrospective cohort study ,Immune dysregulation ,medicine.disease ,Body weight ,medicine.disease_cause ,Affect (psychology) ,Obesity ,Internal medicine ,Medicine ,business ,Body mass index ,Diffuse large B-cell lymphoma - Abstract
e19554 Background: Obesity is associated with a pro-inflammatory state and immune dysregulation. Retrospective studies indicate that obesity could affect toxicities and outcomes after immunotherapies including checkpoint inhibitors and allogeneic stem cell transplant. Currently, there are no data specifically on outcomes for obese patients who receive chimeric antigen receptor T (CAR-T) cells. We described the clinical outcome in obese patients with large B cell lymphoma (LBCL) who received axicabtagene ciloleucel (axi-cel). Methods: We analyzed the effect of body weight (BW) and body mass index (BMI) on toxicities and outcomes of 78 adults with LBCL who received axi-cel between June 2016 and October 2020 at Mayo Clinic. Obesity was defined as having BMI of 30 or higher. Results: Of 78 patients, 22 (28%) and 19 (24%) were classified as overweight (BMI 25-29.99 kg/m2) and obese (BMI ≥30 kg/m2), respectively. Baseline characteristics were not statistically significantly different between non-obese and obese patients. The median delivered dose of fludarabine was similar between non-obese and obese patients (89 [0-105] vs 88 [56-94] mg/m2, P=0.32) whereas the median delivered dose of cyclophosphamide was lower in non-obese patients (1503 [1077-1525] vs 1512 [1021-1660] mg/m2, P=0.01). The 30-days cumulative incidence of CRS and ICANS were similar between non-obese and obese patients. BW and BMI were not associated with CRS or ICANS. The overall response rate was 66% (CR 47%) and 68% (CR 53%) in non-obese and obese group, respectively ( P=0.83). The 1-year event free survival (EFS) and overall survival (OS) was 34.6% and 64.5%, neither were different between non-obese and obese patients (EFS 35.8% vs. 30.7%, P=0.60; OS 59.4% vs. 83.9%, P=0.18). The 1-year cumulative incidence of relapse and non-relapse mortality was comparable (60.8% vs. 69.0%, P=0.40 and 3.4% vs. 0%, P=0.42). In the Cox proportional hazards model, higher dose of fludarabine, but not cyclophosphamide, was associated with better EFS and OS; however, neither obesity nor BW were associated with toxicities and outcomes. Conclusions: In our study, Obesity was not associated with risk of toxicities or adverse survival outcomes. The effect of obesity on the pattern of LD chemotherapy dosing including toxicities and outcomes after CAR-T warrants further exploration. [Table: see text]
- Published
- 2021
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