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1.
Autologous and Allogeneic Hematopoietic Cell Transplantation for Diffuse Large B-cell Lymphoma-Type Richter Syndrome
Herrera, A. F., Ahn, K. W., Litovich, C. A., Chen, Y., Assal, A., Bashir, Q., Bayer, R. L., Coleman, M., DeFilipp, Z., Farhadfar, N., et al
Blood advances. 2021
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Abstract
Richter syndrome (RS) represents a transformation from chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) to an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL), associated with a dismal prognosis. Patients with DLBCL-RS have poor outcomes with DLBCL-directed therapy, thus consolidation with hematopoietic cell transplantation (HCT) has been used with durable remissions observed. Studies reporting HCT outcomes in patients with DLBCL-RS have been small, have not evaluated the prognostic impact of cytogenetic risk factors, and were conducted prior to the era of novel, targeted therapy of CLL/SLL. We performed a CIBMTR registry study evaluating outcomes after autologous (auto, n=53) and allogeneic (allo, n=118) HCT in patients with DLBCL-RS treated in the modern era. More auto-HCT recipients were in complete response at HCT relative to allo-HCT recipients (66% versus 34%), while a higher proportion of allo-HCT recipients had 17p deletion (33% versus 7%) and had previously received novel agents (39% versus 10%). In the auto-HCT cohort, the 3-year relapse incidence, progression-free survival (PFS), and overall survival (OS) were 37%, 48%, and 57%, respectively. Among allo-HCT recipients, the 3-year relapse incidence, PFS, and OS were 30%, 43%, and 52%, respectively. In the allo-HCT cohort, deeper response at HCT was associated with outcomes (3y PFS/OS: 66%/77% CR versus 43%/57% PR versus 5%/15% resistant, p<.0001 for both), while cytogenetic abnormalities and prior novel therapy did not impact outcomes. In our study, HCT resulted in durable remissions in therapy-sensitive patients with DLBCL-RS treated in the era of targeted CLL/SLL therapy, including patients with high-risk features.
PICO Summary
Population
Patients reported to the CIBMTR registry undergoing transplant for diffuse large B-cell lymphoma-type Richter syndrome (n=171)
Intervention
Autologous transplantation (auto, n=53)
Comparison
Allogeneic transplantation (allo, n=118)
Outcome
More auto-HCT recipients were in complete response at HCT relative to allo-HCT recipients (66% versus 34%), while a higher proportion of allo-HCT recipients had 17p deletion (33% versus 7%) and had previously received novel agents (39% versus 10%). In the auto-HCT cohort, the 3-year relapse incidence, progression-free survival (PFS), and overall survival (OS) were 37%, 48%, and 57%, respectively. Among allo-HCT recipients, the 3-year relapse incidence, PFS, and OS were 30%, 43%, and 52%, respectively. In the allo-HCT cohort, deeper response at HCT was associated with outcomes (3y PFS/OS: 66%/77% CR versus 43%/57% PR versus 5%/15% resistant), while cytogenetic abnormalities and prior novel therapy did not impact outcomes.
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Outcome of Allogeneic Transplantation for Mature T-cell Lymphomas: Impact of Donor Source and Disease Characteristics
Hamadani, M., Ngoya, M., Sureda, A., Bashir, Q., Litovich, C. A., Finel, H., Chen, Y., Boumendil, A., Zain, J., Castagna, L., et al
Blood advances. 2021
Abstract
Mature T-cell lymphomas constitute the most common indication of allogeneic hematopoietic cell transplantation (allo-HCT) in lymphomas. Large studies evaluating contemporary outcomes of allo-HCT in mature T-cell lymphomas, relative to commonly used donor sources are not available. Included in this registry study were adult patients who had undergone allo-HCT for anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma (AITL), or peripheral T-cell lymphoma-NOS (PTCL-NOS) between 2008 and 2018. HCT platforms compared were post-transplant cyclophosphamide-based haploidentical (haplo-) HCT, matched sibling donor (MSD) HCT, matched unrelated donor HCT with in-vivo T-cell depletion (MUD TCD+), and MUD HCT without TCD (MUD TCD-). Co-primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints included non-relapse mortality (NRM), and relapse/progression incidence (RI). 1942 patients were eligible (haplo-HCT 237; MSD 911; MUD-TCD+ 468; MUD TCD- 326). Cohorts were comparable for baseline characteristics except higher proportions of patients with decreased performance status (PS) and marrow graft recipients in the haplo-HCT group. On univariate and multivariate comparisons, OS and PFS, RI, and NRM were not significantly different between haplo-HCT, MSD, MUD-TCD+, and MUD-TCD- cohorts, with 3-year OS and PFS of 60%, 63%, 59%, and 64%; and 50%, 50%, 48%, and 52%, respectively. Significant predictors of inferior OS and PFS on multivariate analysis were active disease status at HCT and decreased PS. AITL was associated with significantly reduced relapse risk and better PFS compared to PTCL-NOS. Allo-HCT can provide durable PFS in patients with mature T-cell lymphoma. Outcomes of haplo-HCT were comparable to that of matched donor allo-HCT.
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Autologous Transplant versus Chimeric Antigen Receptor T-cell Therapy for Relapsed DLBCL in Partial Remission
Shadman, M., Pasquini, M. C., Ahn, K. W., Chen, Y., Turtle, C. J., Hematti, P., Cohen, J. B., Khimani, F., Ganguly, S., Merryman, R. W., et al
Blood. 2021
Abstract
The relative efficacy of autologous hematopoietic cell transplant (auto-HCT) versus chimeric antigen receptor T-cell (CAR-T) therapy in diffuse large B-cell lymphoma (DLBCL) patients who achieve a partial remission (PR) after salvage chemotherapy is not known. Using the Center for International Blood & Marrow Transplant Research registry database, we identified adult DLBCL patients who received either an auto-HCT (2013-2019) or CAR-T treatment with axicabtagene ciloleucel (2018-2019) while in a PR by CT or PET scan. We compared the clinical outcomes between the two cohorts using univariable and multivariable regression models after adjustment for relevant baseline and clinical factors. In the univariable analysis, the 2-year progression-free survival (52% vs. 42% ; p=0.1) and the rate of 100-day non-relapse mortality (4% vs. 2% ; p=0.3) were not different between the 2 cohorts but consolidation with auto-HCT was associated with a lower rate of relapse/progression (40% vs. 53% ; p=0.05) and a superior overall survival (OS) (69% vs. 47% ; p=0.004) at 2-years. In the multivariable regression analysis, treatment with auto-HCT was associated with a significantly lower risk of relapse/progression rate (HR=1.49; p=0.01) and a superior OS (HR=1.63; p=0.008). In patients with DLBCL in a PR after salvage therapy, treatment with auto-HCT was associated with a lower incidence of relapse and a superior OS compared with CAR-T. These data support the role of auto-HCT as the standard-of-care in transplant-eligible patients with relapsed DLBCL in PR after salvage therapy.
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4.
Effect of time to relapse on overall survival in patients with mantle cell lymphoma following autologous haematopoietic cell transplantation
Riedell, P. A., Hamadani, M., Ahn, K. W., Litovich, C., Brunstein, C. G., Cashen, A. F., Cohen, J. B., Epperla, N., Hill, B. T., Im, A., et al
British journal of haematology. 2021
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Abstract
In young and fit patients with mantle cell lymphoma (MCL), intensive induction therapy followed by a consolidative autologous haematopoietic cell transplant (autoHCT) is the standard of care in the front-line setting. Recently, time-to-event analysis has emerged as an important risk assessment tool in lymphoma, though its impact in MCL is not well defined. We utilized the Center for International Blood and Marrow Transplant Research database to evaluate the effect of post-autoHCT time to relapse on overall survival (OS) over time in 461 patients who underwent autoHCT within 12 months of MCL diagnosis. On multivariate analysis, the impact of relapse on OS was greatest at the six-month [hazard ratio (HR) = 7·68], 12-month (HR = 6·68), and 18-month (HR = 5·81) landmark timepoints. Using a dynamic landmark model we demonstrate that adjusted OS at five years following each landmark timepoint improved with time for relapsing and non-relapsing patients. Furthermore, early relapse (<18 months) following autoHCT defines a high-risk group with inferior post-relapse OS. This retrospective analysis highlights the impact of time to relapse on OS in MCL patients undergoing up-front autoHCT and emphasizes the need to consider novel therapeutic approaches for patients suffering early relapse.
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Outcomes of Medicare-age eligible NHL patients receiving RIC allogeneic transplantation: a CIBMTR analysis
Shah, N. N., Ahn, K. W., Litovich, C., Fenske, T. S., Ahmed, S., Battiwalla, M., Bejanyan, N., Dahi, P. B., Bolanos-Meade, J., Chen, A. I., et al
Blood advances. 2018;2(8):933-940
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Abstract
The application of allogeneic hematopoietic cell transplantation (allo-HCT) in non-Hodgkin lymphoma (NHL) patients ≥65 years in the United States is limited by lack of Medicare coverage for this indication. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we report allo-HCT outcomes of NHL patients aged ≥65 years (older cohort; n = 446) compared with a cohort of younger NHL patients aged 55-64 years (n = 1183). We identified 1629 NHL patients undergoing a first reduced-intensity conditioning (RIC) or nonmyeloablative conditioning allo-HCT from 2008 to 2015 in the United States. Cord blood or haploidentical transplants were excluded. The median age was 68 years (range 65-77) for the older cohort vs 60 years (range 55-64) in the younger cohort. The 4-year adjusted probabilities of nonrelapse mortality (NRM), relapse/progression (R/P), progression-free survival (PFS), and overall survival (OS) of the younger and older groups were 24% vs 30% (P = .03), 41% vs 42% (P = .82), 37% vs 31% (P = .03), and 51% vs 46% (P = .07), respectively. Using multivariate analysis, compared with the younger group, the older cohort was associated with increased NRM, but there was no difference between the 2 cohorts in terms of R/P, PFS, or OS. The most common cause of death was disease relapse in both groups. In NHL patients eligible for allo-HCT, there was no difference in OS between the 2 cohorts. Age alone should not determine allo-HCT eligibility in NHL, and Medicare should expand allo-HCT coverage to older adults.
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Reduced-Intensity Transplantation for Lymphomas Using Haploidentical Related Donors Versus HLA-Matched Sibling Donors: A Center for International Blood and Marrow Transplant Research Analysis
Ghosh, N., Karmali, R., Rocha, V., Ahn, K. W., DiGilio, A., Hari, P. N., Bachanova, V., Bacher, U., Dahi, P., de Lima, M., et al
Journal of Clinical Oncology. 2016;34(26):3141-9
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Abstract
PURPOSE Related donor haploidentical hematopoietic cell transplantation (Haplo-HCT) using post-transplantation cyclophosphamide (PT-Cy) is increasingly used in patients lacking HLA-matched sibling donors (MSD). We compared outcomes after Haplo-HCT using PT-Cy with MSD-HCT in patients with lymphoma, using the Center for International Blood and Marrow Transplant Research registry. MATERIALS AND METHODS We evaluated 987 adult patients undergoing either Haplo-HCT (n = 180) or MSD-HCT (n = 807) following reduced-intensity conditioning regimens. The haploidentical group received graft-versus-host disease (GVHD) prophylaxis with PT-Cy with or without a calcineurin inhibitor and mycophenolate. The MSD group received calcineurin inhibitor-based GVHD prophylaxis. RESULTS Median follow-up of survivors was 3 years. The 28-day neutrophil recovery was similar in the two groups (95% v 97%; P = .31). The 28-day platelet recovery was delayed in the haploidentical group compared with the MSD group (63% v 91%; P = .001). Cumulative incidence of grade II to IV acute GVHD at day 100 was similar between the two groups (27% v 25%; P = .84). Cumulative incidence of chronic GVHD at 1 year was significantly lower after Haplo-HCT (12% v 45%; P < .001), and this benefit was confirmed on multivariate analysis (relative risk, 0.21; 95% CI, 0.14 to 0.31; P < .001). For Haplo-HCT v MSD-HCT, 3-year rates of nonrelapse mortality (15% v 13%; P = .41), relapse/progression (37% v 40%; P = .51), progression-free survival (48% v 48%; P = .96), and overall survival (61% v 62%; P = .82) were similar. Multivariate analysis showed no significant difference between Haplo-HCT and MSD-HCT in terms of nonrelapse mortality (P = .06), progression/relapse (P = .10), progression-free survival (P = .83), and overall survival (P = .34). CONCLUSION Haplo-HCT with PT-Cy provides survival outcomes comparable to MSD-HCT, with a significantly lower risk of chronic GVHD. Copyright © 2016 by American Society of Clinical Oncology.