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Impact of Second Primary Malignancy Post-Autologous Transplantation on Outcomes of Multiple Myeloma: A CIBMTR Analysis
Ragon, B. K., Shah, M. V., D'Souza, A., Estrada-Merly, N., Gowda, L., George, G., DeLima, M., Hashmi, S., Kharfan-Dabaja, M. A., Majhail, N. S., et al
Blood advances. 2023
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Abstract
The overall survival (OS) has improved significantly in multiple myeloma (MM) over the last decade with use of proteasome inhibitor and immunomodulatory drug-based combinations, followed by high-dose melphalan and autologous hematopoietic stem cell transplantation (auto-HSCT) and subsequent maintenance therapies in eligible newly diagnosed patients. However, clinical trials employing auto-HSCT followed by lenalidomide maintenance have shown an increased risk of second primary malignancies (SPM), including second hematological malignancies (SHM). We evaluated the impact of SPM and SHM on progression-free survival (PFS) and OS in MM patients following auto-HSCT using CIBMTR registry data. Adult MM patients who underwent first auto-HSCT in the United States with melphalan conditioning regimen from 2011 to 2018 and received maintenance therapy were included (n=3,948). At a median follow up of 37 months, 175 (4%) patients developed SPM, including 112 (64%) solid, 36 (20%) myeloid, 24 (14%) SHM, not otherwise specified, and 3 (2%) lymphoid malignancies. Multivariate analysis demonstrated that SPM and SHM were associated with an inferior PFS (HR 2.62, P<.001 and HR 5.01, P<.001, respectively) and OS (HR 3.85, P<.001 and HR 8.13, P<.001, respectively). In patients who developed SPM and SHM, MM remained the most frequent primary cause of death (42% versus 30% and 53% versus 18%, respectively). We conclude the development of SPM and SHM leads to a poor survival in MM patients and is an important survivorship challenge. Given the median survival for MM continues to improve, continued vigilance is needed to assess the risks of SPM and SHM with maintenance therapy post-auto-HSCT.
PICO Summary
Population
Drawn from the CIBMTR registry, adults with multiple myeloma (MM) who underwent first auto-HSCT with melphalan conditioning regimen and received maintenance therapy (n=3,948)
Intervention
Identification of second primary malignancies (SPM) or second haematological malignancies (SHM) following HSCT.
Comparison
None
Outcome
At a median follow up of 37 months, 175 (4%) patients developed SPM, including 112 (64%) solid, 36 (20%) myeloid, 24 (14%) SHM, not otherwise specified, and 3 (2%) lymphoid malignancies. Multivariate analysis demonstrated that SPM and SHM were associated with an inferior PFS (HR 2.62 and HR 5.01 respectively) and OS (HR 3.85, and HR 8.13, respectively). In patients who developed SPM and SHM, MM remained the most frequent primary cause of death (42% versus 30% and 53% versus 18%, respectively).
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A Calcineurin Inhibitor Free Graft Versus Host Disease Prophylaxis for Patients Undergoing Matched Related and Matched Unrelated Donor Allogeneic Hematopoietic Cell Transplant
Iqbal, M., Nieto, F. A. M., Brannick, K. M., Li, Z., Murthy, H., Foran, J., Roy, V., Kharfan-Dabaja, M. A., Ayala, E.
Transplantation and cellular therapy. 2023
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Editor's Choice
Abstract
Post-transplantation cyclophosphamide (PTCy) and calcineurin inhibitor (CNI) based graft versus host disease (GVHD) prophylaxis has shown lower rates of acute and chronic GVHD when compared with the traditional prophylaxis of CNI and methotrexate (MTX) in matched related (MRD) and matched unrelated donor (MUD) allogeneic hematopoietic cell transplant (allo-HCT). The combination of PTCy with sirolimus as a CNI-free GVHD prophylaxis has shown promising results with cumulative rates of grade II-IV acute and chronic GVHD in the range of 15-27% and 20-27%, respectively, in patients undergoing MRD, MUD and haploidentical allo-HCT. We report a single center, nonrandomized comparison of patients undergoing matched donor allo-HCT receiving PTCy in combination with sirolimus (PTCy-Siro) with those receiving the standard GVHD prophylaxis of tacrolimus and MTX (Tac-MTX). One hundred and sixteen consecutive patients who had undergone a MRD or MUD allo-HCT between January 2018 to January 2021 and received either PTCy with sirolimus or tacrolimus with methotrexate as GVHD prophylaxis regimens were eligible for inclusion. Out of a total of 116 patients undergoing MRD and MUD allo-HCT, 29 received PTCy-Siro and 87 Tac-MTX. Patients receiving PTCy-Siro had a significantly shorter median time to immunosuppression withdrawal at 138 (37-312) vs 232(66-1120) days for patients receiving Tac-MTX (p=<0.001). No significant difference was observed between the two arms for incidence of grade II to IV acute GVHD, grade III to IV acute GVHD, steroid refractory acute GVHD or clinical infections. At a median follow up of 1.1 (range: 0-1.8) years, patients receiving PTCy-Siro were significantly less likely to have chronic GVHD with 2-year freedom from GVHD of 75% (95%CI: 58-98%) vs 20% (95%CI 10-40%), p=0.005.
PICO Summary
Population
Adults from a single centre in USA undergoing matched-related or matched-unrelated donor allogeneic HSCT (n=116)
Intervention
Post-transplant cyclophosphamide in combination with sirolimus (PTCy-Siro, n=29)
Comparison
Tacrolimus and methotrexate (Tac-MTX, n=87)
Outcome
Patients receiving PTCy-Siro had a significantly shorter median time to immunosuppression withdrawal at 138 (37-312) vs 232(66-1120) days for patients receiving Tac-MTX. No significant difference was observed between the two arms for incidence of grade II to IV acute GVHD, grade III to IV acute GVHD, steroid refractory acute GVHD or clinical infections. At a median follow up of 1.1 (range: 0-1.8) years, patients receiving PTCy-Siro were significantly less likely to have chronic GVHD with 2-year freedom from GVHD of 75% (95%CI: 58-98%) vs 20% (95%CI 10-40%)
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3.
A Simple Prognostic System in Myelofibrosis Patients Undergoing Allogeneic Stem Cell Transplant: A CIBMTR/EBMT analysis
Tamari, R., McLornan, D. P., Ahn, K. W., Estrada-Merly, N., Hernandez-Boluda, J. C., Giralt, S. A., Palmer, J. M., Gale, R. P., DeFilipp, Z., Marks, D., et al
Blood advances. 2023
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Editor's Choice
Abstract
To develop a prognostic model for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT) for myelofibrosis (MF). We examined 623 patients undergoing allo-HCT between 2000 - 2016 in the USA (CIBMTR cohort). A Cox multivariable model was used to identify factors prognostic of mortality. A weighted score using these factors was assigned to patients transplanted in Europe (EBMT cohort) (n = 623). Age above 50 (hazard ratio [HR], 1.39; 95% confidence interval [CI], 0.98 -1.96), and HLA matched unrelated donor (HR, 1.29; 95% CI, 0.98-1.7) were associated with increased hazard of death and were assigned 1 point. Hemoglobin lower than 100g/L at time of transplant (HR, 1.63; 95% CI, 1.2- 2.19), and a mismatched unrelated donor (HR, 1.78; 95% CI, 1.25- 2.52), were assigned 2 points. The 3-year overall survival (OS) in patients with a low (1-2 points), intermediate (3-4 points) and high score (5 points) were 69% (95% CI, 61% -76 %), 51 % (95% CI, 46% -56.4 %), and 34% (95% CI, 21% - 49%), respectively (P. < 0.001). Increasing score was predictive of increased transplant related mortality (TRM) (P .0017) but not for relapse (P. 0.12). The derived score was predictive for OS (P. < 0.001) and TRM (P. 0.002) but not relapse (P. 17) in the EBMT cohort as well. The proposed system was prognostic of survival in two large cohorts, CIBMTR and EBMT, and can easily be applied by clinicians consulting patients with MF on transplant outcomes.
PICO Summary
Population
Adults aged 40 or over undergoing allogeneic transplantation for myelofibrosis and reported to the CIBMTR or EBMT registries (n=1246)
Intervention
Cox regression model of prognostic factors developed with patients from the CIBMTR registry (n=623)
Comparison
Validation of the model using a cohort from the EBMT registry (n=623)
Outcome
Age above 50 (hazard ratio [HR], 1.39; 95% confidence interval [CI], 0.98 -1.96), and HLA matched unrelated donor (HR, 1.29; 95% CI, 0.98-1.7) were associated with increased hazard of death and were assigned 1 point. Hemoglobin lower than 100g/L at time of transplant (HR, 1.63; 95% CI, 1.2- 2.19), and a mismatched unrelated donor (HR, 1.78; 95% CI, 1.25- 2.52), were assigned 2 points. The 3-year overall survival (OS) in patients with a low (1-2 points), intermediate (3-4 points) and high score (5 points) were 69% (95% CI, 61% -76 %), 51 % (95% CI, 46% -56.4 %), and 34% (95% CI, 21% - 49%), respectively. Increasing score was predictive of increased transplant related mortality (TRM) but not for relapse. The derived score was predictive for OS and TRM but not relapse in the EBMT cohort as well.
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Impact of pre-transplant induction and consolidation cycles on AML allogeneic transplant outcomes: a CIBMTR analysis in 3113 AML patients
Boyiadzis, M., Zhang, M. J., Chen, K., Abdel-Azim, H., Abid, M. B., Aljurf, M., Bacher, U., Badar, T., Badawy, S. M., Battiwalla, M., et al
Leukemia. 2022
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Editor's Choice
Abstract
We investigated the impact of the number of induction/consolidation cycles on outcomes of 3113 adult AML patients who received allogeneic hematopoietic cell transplantation (allo-HCT) between 2008 and 2019. Patients received allo-HCT using myeloablative (MAC) or reduced-intensity (RIC) conditioning in first complete remission (CR) or with primary induction failure (PIF). Patients who received MAC allo-HCT in CR after 1 induction cycle had 1.3-fold better overall survival (OS) than 2 cycles to CR and 1.47-fold better than ≥3 cycles. OS after CR in 2 or ≥3 cycles was similar. Relapse risk was 1.65-fold greater in patients receiving ≥3 cycles to achieve CR. After RIC allo-HCT, the number of induction cycles to CR did not affect OS. Compared to CR in 1 cycle, relapse risk was 1.24-1.41-fold greater in patients receiving 2 or ≥3 cycles. For patients receiving only 1 cycle to CR, consolidation therapy prior to MAC allo-HCT was associated with improved OS vs. no consolidation therapy. Detectable MRD at the time of MAC allo-HCT did not impact outcomes while detectable MRD preceding RIC allo-HCT was associated with an increased risk of relapse. For allo-HCT in PIF, OS was significantly worse than allo-HCT in CR after 1-3 cycles.
PICO Summary
Population
Adults with acute lymphoblastic leukaemia who received allogeneic hematopoietic cell transplantation (allo-HCT) in 450 centres worldwide (n=3113)
Intervention
Patients achieving complete remission (CR) after 1 induction cycle (n=862)
Comparison
Patients requiring 2 cycles to CR (n=454) or 3 or more cycles to CR (n=157).
Outcome
Patients who received myeloablative (MAC) allo-HCT in CR after 1 induction cycle had 1.3-fold better overall survival (OS) than 2 cycles to CR and 1.47-fold better than ≥3 cycles. OS after CR in 2 or ≥3 cycles was similar. Relapse risk was 1.65-fold greater in patients receiving ≥3 cycles to achieve CR. After reduced-intensity conditioning (RIC) allo-HCT, the number of induction cycles to CR did not affect OS. Compared to CR in 1 cycle, relapse risk was 1.24-1.41-fold greater in patients receiving 2 or ≥3 cycles. For patients receiving only 1 cycle to CR, consolidation therapy prior to MAC allo-HCT was associated with improved OS vs. no consolidation therapy. Detectable MRD at the time of MAC allo-HCT did not impact outcomes while detectable MRD preceding RIC allo-HCT was associated with an increased risk of relapse. For allo-HCT in PIF, OS was significantly worse than allo-HCT in CR after 1-3 cycles.
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5.
Relapse and Disease-Free Survival in Patients With Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation Using Older Matched Sibling Donors vs Younger Matched Unrelated Donors
Guru Murthy, G. S., Kim, S., Hu, Z. H., Estrada-Merly, N., Abid, M. B., Aljurf, M., Bacher, U., Badawy, S. M., Beitinjaneh, A., Bredeson, C., et al
JAMA oncology. 2022
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Editor's Choice
Abstract
IMPORTANCE Matched sibling donors (MSDs) are preferred for allogeneic hematopoietic cell transplantation (allo-HCT) in myelodysplastic syndrome even if they are older. However, whether older MSDs or younger human leukocyte antigen-matched unrelated donors (MUDs) are associated with better outcomes remains unclear. OBJECTIVE To investigate whether allo-HCT for myelodysplastic syndrome using younger MUDs would be associated with improved disease-free survival and less relapse compared with older MSDs. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study assessed data reported to the Center for International Blood and Marrow Transplant Research database from 1761 adults 50 years or older with myelodysplastic syndrome who underwent allo-HCT using an older MSD or younger MUD between January 1, 2011, and December 31, 2017, with a median follow-up of 48 months. Data analysis was performed from January 8, 2019, to December 30, 2020. INTERVENTIONS/EXPOSURES Allo-HCT from an older MSD (donor age ≥50 years) or a younger MUD (donor age ≤35 years). MAIN OUTCOMES AND MEASURES The primary outcome was disease-free survival. Secondary outcomes were overall survival, relapse, nonrelapse mortality, acute graft-vs-host disease (GVHD), chronic GVHD, and GVHD-free relapse-free survival. RESULTS Of 1761 patients (1162 [66%] male; median [range] age, 64.9 [50.2-77.6] years in the MSD cohort and 66.5 [50.4-80.9] years in MUD cohort), 646 underwent allo-HCT with an older MSD and 1115 with a younger MUD. In multivariable analysis, the rate of disease-free survival was significantly lower in allo-HCTs with older MSDs compared with younger MUDs (hazard ratio [HR], 1.17; 95% CI, 1.02-1.34; P = .02), whereas the difference in overall survival rate of allo-HCT with younger MUDs vs older MSDs was not statistically significant (HR, 1.13; 95% CI, 0.98-1.29; P = .07). Allo-HCT with older MSDs was associated with significantly higher relapse (HR, 1.62; 95% CI, 1.32-1.97; P < .001), lower nonrelapse mortality (HR, 0.76; 95% CI, 0.59-0.96; P = .02), lower acute GVHD (HR, 0.52; 95% CI, 0.42-0.65; P < .001), chronic GVHD (HR, 0.77; 95% CI, 0.64-0.92; P = .005), and a lower rate of GVHD-free relapse-free survival beyond 12 months after allo-HCT (HR, 1.42; 95% CI, 1.02-1.98; P = .04). CONCLUSIONS AND RELEVANCE This cohort study found higher disease-free survival and lower relapse for allo-HCT in myelodysplastic syndrome using younger MUDs compared with older MSDs. The risk of nonrelapse mortality and GVHD was lower with older MSDs. These results suggest that the use of younger MUDs should be considered in the donor selection algorithm for myelodysplastic syndrome, in which it is pivotal to minimize relapse given limited treatment options for managing relapsed disease.
PICO Summary
Population
People 50 years and older with myelodysplastic syndrome, identified from the CIBMTR database (n=1761)
Intervention
Matched sibling donor transplantation from an older donor 50 years and over (older MSD, n=646)
Comparison
Matched unrelated donor transplantation from a younger donor 35 years and under (younger MUD, n=1115)
Outcome
In multivariable analysis, the rate of disease-free survival was significantly lower in allo-HCTs with older MSDs compared with younger MUDs (hazard ratio [HR], 1.17; 95% CI, 1.02-1.34), whereas the difference in overall survival rate of allo-HCT with younger MUDs vs older MSDs was not statistically significant (HR, 1.13; 95% CI, 0.98-1.29). Allo-HCT with older MSDs was associated with significantly higher relapse (HR, 1.62; 95% CI, 1.32-1.97;), lower nonrelapse mortality (HR, 0.76; 95% CI, 0.59-0.96;), lower acute GVHD (HR, 0.52; 95% CI, 0.42-0.65), chronic GVHD (HR, 0.77; 95% CI, 0.64-0.92), and a lower rate of GVHD-free relapse-free survival beyond 12 months after allo-HCT (HR, 1.42; 95% CI, 1.02-1.98).
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Allogeneic haematopoietic cell transplant in patients with relapsed/refractory anaplastic large cell lymphoma
Furqan, F., Ahn, K. W., Chen, Y., Kaur, M., Abutalib, S. A., Ahmed, N., Ahmed, S., Kharfan-Dabaja, M. A., Friedberg, J., Gregory, T., et al
British journal of haematology. 2022
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Editor's Choice
Abstract
The prognosis of relapsed/refractory (R/R) anaplastic large cell lymphoma (ALCL) is poor. Large studies evaluating outcomes of allogeneic haematopoietic cell transplantation (allo-HCT) in systemic R/R ALCL are not available. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we evaluated outcomes of 182 adults (aged ≥18 years) with R/R ALCL undergoing allo-HCT between 2008 and 2019. Non-relapse mortality (NRM), disease relapse/progression (REL), progression-free survival (PFS), and overall survival (OS) were modelled using Cox proportional hazards models. The median (range) follow-up of survivors was 62 (3-148) months. The 1-year NRM was 18%. The 5-year REL, PFS and OS were 32%, 41% and 56% respectively. On multivariable regression analysis African American race (hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.6-4.8; p < 0.001) and refractory disease at allo-HCT (HR 3.2, 95% CI 1.6-6.2; p < 0.001) were predictive of inferior OS. Similarly, African-American race (HR 2.1, 95% CI 1.3-3.4; p = 0.003), other minority race (HR 2.5, 95% CI 1.2-5.3; p = 0.02) and refractory disease (HR 2.2, 95% CI 1.2-4.3; p = 0.01) were predictive of inferior PFS. These data, demonstrate that allo-HCT can result in durable disease control in a sizable proportion of patients with R/R ALCL. Refractory disease and racial minority status predicted inferior allo-HCT outcomes. Whether the inferior outcomes of racial minorities with R/R ALCL after allo-HCT are driven by differences in disease biology or disparities in post allo-HCT care, or both, requires further investigation.
PICO Summary
Population
Adults with relapsed/refractory anaplastic large cell lymphoma identified from the CIBMTR database (n=182)
Intervention
Allogeneic HSCT
Comparison
None
Outcome
The median (range) follow-up of survivors was 62 (3-148) months. The 1-year non-relapse mortality (NRM) was 18%. The 5-year disease relapse/progression (REL), progression-free survival (PFS) and overall survival (OS) were 32%, 41% and 56% respectively. On multivariable regression analysis African American race (hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.6-4.8) and refractory disease at allo-HCT (HR 3.2, 95% CI 1.6-6.2) were predictive of inferior OS. Similarly, African-American race (HR 2.1, 95% CI 1.3-3.4), other minority race (HR 2.5, 95% CI 1.2-5.3) and refractory disease (HR 2.2, 95% CI 1.2-4.3) were predictive of inferior PFS.
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7.
Outcomes of Allogeneic Hematopoietic Cell Transplantation in T-cell Prolymphocytic Leukemia: A Contemporary Analysis from the Center for International Blood and Marrow Transplant Research
Murthy, H. S., Ahn, K. W., Estrada-Merly, N., Alkhateeb, H. B., Bal, S., Kharfan-Dabaja, M. A., Dholaria, B., Foss, F., Gowda, L., Jagadeesh, D., et al
Transplantation and cellular therapy. 2022
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Editor's Choice
Abstract
BACKGROUND T-cell prolymphocytic leukemia (T-PLL) is a rare, aggressive malignancy with limited treatment options and poor long-term survival. Previous studies of allogeneic hematopoietic cell transplantation (alloHCT) for T-PLL are limited by small numbers, and descriptions of patient and transplant characteristics and outcomes after alloHCT are sparse. OBJECTIVE To describe outcomes of alloHCT in T-PLL and identify predictors of post-transplant relapse and survival. STUDY DESIGN We conducted an analysis of data using the Center for International Blood and Marrow Transplant Research (CIBMTR) database on 266 patients with T-PLL who underwent alloHCT during 2008-2018. RESULTS The 4-year rates of overall survival (OS), disease-free survival (DFS), relapse, and treatment-related mortality (TRM) were 30.0% (95% CI, 23.8-36.5%), 25.7% (95% CI, 20-32%), 41.9% (95% CI, 35.5-48.4%), and 32.4% (95% CI, 26.4-38.6%), respectively. In multivariable analyses, three variables were associated with inferior OS: myeloablative conditioning (MAC) (hazard ratio [HR] 2.18, p<0.0001); age older than 60 years (HR 1.61, p=0.0053); and suboptimal performance status defined by Karnofsky Performance Status (KPS) <90 (HR 1.53, p=0.0073). MAC also was associated with increased TRM (HR 3.31, p<0.0001), increased cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) (HR 2.94, p=0.0011) and an inferior disease-free survival (HR 1.86, p=0.0004). Conditioning intensity was not associated with relapse; however stable disease/progression correlated with increased risk of relapse (HR 2.13, p=0.0072). Both in vivo T cell depletion (TCD) as part of conditioning and KPS <90 were associated with worse TRM and inferior DFS. Total Body Irradiation was not found to have any significant effect on OS, DFS or TRM. CONCLUSION Our data showed that reduced-intensity conditioning without in vivo T-cell depletion (that is, without ATG or alemtuzumab) prior to alloHCT was associated with long-term disease-free survival in patients with T-PLL who were 60 or younger or who had KPS >90 or had chemo-sensitive disease.
PICO Summary
Population
People with T-cell prolymphocytic leukaemia (T-PLL), identified from the CIBMTR database (n=266)
Intervention
Allogeneic haematopoietic stem cell transplantation
Comparison
None
Outcome
The 4-year rates of overall survival (OS), disease-free survival (DFS), relapse, and treatment-related mortality (TRM) were 30.0% (95% CI, 23.8-36.5%), 25.7% (95% CI, 20-32%), 41.9% (95% CI, 35.5-48.4%), and 32.4% (95% CI, 26.4-38.6%), respectively. In multivariable analyses, three variables were associated with inferior OS: myeloablative conditioning (MAC) (hazard ratio [HR] 2.18); age older than 60 years (HR 1.61); and suboptimal performance status defined by Karnofsky Performance Status (KPS) <90 (HR 1.53). MAC also was associated with increased TRM (HR 3.31), increased cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) (HR 2.94) and an inferior disease-free survival (HR 1.86). Conditioning intensity was not associated with relapse; however stable disease/progression correlated with increased risk of relapse (HR 2.13). Both in vivo T cell depletion (TCD) as part of conditioning and KPS <90 were associated with worse TRM and inferior DFS. Total Body Irradiation was not found to have any significant effect on OS, DFS or TRM.
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8.
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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Editor's Choice
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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9.
A phase 2 trial of GVHD prophylaxis with PTCy, sirolimus, and MMF after peripheral blood haploidentical transplantation
Bejanyan, N., Pidala, J. A., Wang, X., Thapa, R., Nishihori, T., Elmariah, H., Lazaryan, A., Khimani, F., Davila, M. L., Mishra, A., et al
Blood advances. 2021;5(5):1154-1163
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Editor's Choice
Abstract
The introduction of posttransplant cyclophosphamide (PTCy) made performing allogeneic hematopoietic cell transplantation (HCT) from HLA haplotype-incompatible donors possible. In a setting of PTCy and tacrolimus/mycophenolate mofetil (MMF) as a graft-versus-host disease (GVHD) prophylaxis, a peripheral blood (PB) graft source as compared with bone marrow reduces the relapse rate but increases acute GVHD (aGVHD) and chronic GVHD (cGVHD). This phase 2 trial assessed sirolimus and MMF efficacy following PTCy as a GVHD prophylaxis after PB haploidentical HCT (haplo-HCT). With 32 evaluable patients (=18 years) enrolled, this study had 90% power to demonstrate a reduction in 100-day grade II-IV aGVHD to 20% from the historical benchmark of 40% after haplo-HCT using PTCy/tacrolimus/MMF. At a median follow-up of 16.1 months, the primary end point of the trial was met with a day-100 grade II-IV aGVHD cumulative incidence of 18.8% (95% confidence interval [CI], 7.5% to 34.0%). There were no graft-failure events and the 1-year probability of National Institutes of Health (NIH) moderate/severe cGVHD was 18.8% (95% CI, 7.4% to 34.0%), nonrelapse mortality was 18.8% (95% CI, 7.4% to 34.0%), relapse was 22.2% (95% CI, 9.6% to 38.2%), disease-free survival was 59.0% (95% CI, 44.1% to 79.0%), GVHD-free relapse-free survival was 49.6% (95% CI, 34.9% to 70.5%), and overall survival was 71.7% (95% CI, 57.7% to 89.2%) for the entire cohort. These data demonstrate that GVHD prophylaxis with sirolimus/MMF following PTCy effectively prevents grade II-IV aGVHD after PB haplo-HCT, warranting prospective comparison of sirolimus vs tacrolimus in combination with MMF following PTCy as GVHD prophylaxis after PB HCT. This trial was registered at www.clinicaltrials.gov as #NCT03018223.
PICO Summary
Population
Adult patients who received a haploidentical stem cell transplant (n=32)
Intervention
Post-transplant cyclophosphamide (PTCy) and tacrolimus/mycophenolate mofetil (MMF) as a graft-versus-host disease (GVHD) prophylaxis
Comparison
None
Outcome
At a median follow-up of 16.1 months, the primary end point of the trial was met with a day-100 grade II-IV aGVHD cumulative incidence of 18.8%. There were no graft-failure events and the 1-year probability of National Institutes of Health (NIH) moderate/severe cGVHD was 18.8%, nonrelapse mortality was 18.8%, relapse was 22.2% , disease-free survival was 59.0%, GVHD-free relapse-free survival was 49.6% and overall survival was 71.7% for the entire cohort.
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10.
Second allogeneic haematopoietic cell transplantation using HLA-matched unrelated versus T-cell replete haploidentical donor and survival in relapsed acute myeloid leukaemia
Kharfan-Dabaja, M. A., Labopin, M., Brissot, E., Kroger, N., Finke, J., Ciceri, F., Deconinck, E., Blaise, D., Chevallier, P., Gramatzki, M., et al
British journal of haematology. 2021
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Editor's Choice
Abstract
Optimal donor choice for a second allogeneic haematopoietic cell transplant (allo-HCT) in relapsed acute myeloid leukaemia (AML) remains unknown. We compared overall survival (OS) using registry data from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT) involving 455 adults who received a second allo-HCT from a human leucocyte antigen (HLA)-matched unrelated (MUD) (n = 320) or a haploidentical (n = 135) donor. Eligibility criteria required adults aged =18 years who received a second allo-HCT for treating AML relapse between 2005 and 2019. The primary end-point was OS. There was no statistically significant difference in the median (interquartile range) age between the groups, MUD 46 (35-58) versus haploidentical 44 (33-53) years (P = 0·07). The median OS was not different between the MUD and the haploidentical groups (10 vs. 11 months, P = 0·57). Similarly, the 2-year OS was 31% for the MUD and 29% for the haploidentical donor groups. The OS was worse if the procedure was performed with active AML [hazard ratio (HR) 1·42, 95% confidence interval (CI) 1·07-1·89; P = 0·02]. Conversely, a longer time from first allo-HCT to relapse (>13·2 months) was associated with better OS (HR 0·50, 95% CI 0·37-0·69; P < 0·0001). The results of the present analysis limit the ability to recommend one donor type over another when considering a second allo-HCT for relapsed AML. Our findings highlight that best OS is achieved when receiving the second allo-HCT in complete remission.
PICO Summary
Population
Adults identified from EBMT registry data who received a second allogeneic transplant for a relapse of acute myeloid leukaemia (n=455)
Intervention
Matched unrelated donor (MUD, n=320)
Comparison
Haploidentical donor (n=135)
Outcome
There was no statistically significant difference in the median (interquartile range) age between the groups, MUD 46 (35-58) versus haploidentical 44 (33-53) years. The median OS was not different between the MUD and the haploidentical groups (10 vs. 11 months). Similarly, the 2-year OS was 31% for the MUD and 29% for the haploidentical donor groups. The OS was worse if the procedure was performed with active AML [hazard ratio (HR) 1·42]. Conversely, a longer time from first allo-HCT to relapse (>13·2 months) was associated with better OS (HR 0·50).