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1.
Outcomes of allogeneic hematopoietic stem cell transplantation for relapsed or refractory diffuse large B-cell lymphoma
Kato, K., Sugio, T., Ikeda, T., Yoshitsugu, K., Miyazaki, K., Suzumiya, J., Yamamoto, G., Kim, S. W., Ikegame, K., Uehara, Y., et al
Bone marrow transplantation. 2023
Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a currative treatment modality for diffuse large B-cell lymphoma (DLBCL) because of the intrinsic graft-versus-lymphoma effect. However, limited information is available regarding which patients with relapsed or refractory DLBCL are likely to benefit from allo-HSCT. We retrospectively analyzed data from 1268 DLBCL patients who received allo-HSCT. The overall survival and progression-free survival (PFS) rates were 30.3% and 21.6% at 3 years, respectively. Multivariate analysis revealed that stable or progressive disease at transplantation, male patient, poorer performance status at transplantation, and shorter intervals from previous transplantation were associated independently with a lower PFS. Four prognostic factors were used to construct a prognostic index for PFS, predicting 3-year PFS of 55.4%, 43.7%, 20.4% and 6.6%, respectively. The prognostic model predicted relapse rates following allo-HSCT accordingly (P < 0.0001), whereas did not predict transplantation-related mortality (P = 0.249). The prognostic index can identify a subgroup of DLBCL patients who benefit from allo-HSCT and it is worthwhile to evaluate whether this model is also applicable to patients undergoing allo-HSCT in cases of relapse after chimeric antigen receptor engineered T-cell therapy, although the application of allo-HSCT has been declining with the increase of novel immunotherapies.
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Allogeneic hematopoietic stem cell transplantation for NK/T-cell lymphoma: an international collaborative analysis
Berning, P., Schmitz, N., Ngoya, M., Finel, H., Boumendil, A., Wang, F., Huang, X. J., Hermine, O., Philippe, L., Couronné, L., et al
Leukemia. 2023;:1-10
Abstract
Natural killer/T-cell lymphomas (NKTCL) represent rare and aggressive lymphoid malignancies. Patients (pts) with relapsed/refractory disease after Asparaginase (ASPA)-based chemotherapy have a dismal prognosis. To better define the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT), we conducted a retrospective analysis of data shared with the European Society for Blood and Marrow Transplantation (EBMT) and cooperating Asian centers. We identified 135 pts who received allo-HSCT between 2010 and 2020. Median age was 43.4 years at allo-HSCT, 68.1% were male. Ninety-seven pts (71.9 %) were European, 38 pts (28.1%) Asian. High Prognostic Index for NKTCL (PINK) scores were reported for 44.4%; 76.3% had >1 treatment, 20.7% previous auto-HSCT, and 74.1% ASPA-containing regimens prior to allo-HSCT. Most (79.3%) pts were transplanted in CR/PR. With a median follow-up of 4.8 years, 3-year progression-free(PFS) and overall survival were 48.6% (95%-CI:39.5-57%) and 55.6% (95%-CI:46.5-63.8%). Non-relapse mortality at 1 year was 14.8% (95%-CI:9.3-21.5%) and 1-year relapse incidence 29.6% (95%-CI:21.9-37.6%). In multivariate analyses, shorter time interval (0-12 months) between diagnosis and allo-HSCT [HR = 2.12 (95%-CI:1.03-4.34); P = 0.04] and transplantation not in CR/PR [HR = 2.20 (95%-CI:0.98-4.95); P = 0.056] reduced PFS. Programmed cell death protein 1(PD-1/PD-L1) treatment before HSCT neither increased GVHD nor impacted survival. We demonstrate that allo-HSCT can achieve long-term survival in approximately half of pts allografted for NKTCL.
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3.
Allogeneic hematopoietic stem cell transplantation in non-Hodgkin lymphoma in Switzerland, 30 years of experience: Sooner is better
Rebmann, E., Nabergoj, M., Grandjean, B., Stakia, P., Stern, A., Medinger, M., Masouridi-Levrat, S., Dantin, C., Schanz, U., Baldomero, H., et al
EJHaem. 2023;4(1):258-261
Abstract
Due to relatively high nonrelapse mortality (NRM), allogeneic hematopoietic stem cell transplantation (allo-HSCT) in non-Hodgkin's lymphoma (NHL) remains the ultimate line of treatment but the only curable approach in a setting of relapse/refractory disease. Here, we conducted a retrospective, multicenter, registry-based analysis on patients who underwent allo-HSCT for NHL in Switzerland, over 30-year (1985-2020) period. The study included 301 allo-HSCTs performed for NHL patients in three University Hospitals of Switzerland (Zurich, Basel and Geneva) 09/1985 to 05/2020. We assessed in univariate and multivariable analysis the impact on survivals (overall survival [OS], relapse free survival [RFS], relapse incidence [RI], and non-treatment related mortality [NRM]). The maximum follow-up was 25 years with median follow-up for alive patients of 61 months. The median age at allo-HSCT was 51 years. Three- and -year OS was - 59.5% and 55.4%; 3- and 5-year PFS was 50% and 44%; 3- and 5-year NRM was 21.7% and 23.6%. RI at 3 and 5 years was 27.4% and 34.9%. In conclusion, our analysis of the entire Swiss experience of allo-HSCT in patients with NHL shows promising 5- and possibly 10-year OS and relatively acceptable NRM rates for such population, the majority being not in complete remission (CR) at the time of transplantation.
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4.
Allogeneic stem cell transplantation achieves long-term remissions in mantle cell lymphoma, including in TP53-mutated disease
Lew, T. E., Cliff, E. R. S., Dickinson, M., Tam, C. S., Seymour, J. F., Blombery, P., Bajel, A., Ritchie, D., Khot, A.
Leukemia & lymphoma. 2023;:1-9
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Editor's Choice
Abstract
Cytarabine-containing chemoimmunotherapy followed by autologous transplantation and rituximab maintenance achieves durable remissions for most patients with mantle cell lymphoma (MCL). However, patients with TP53-mutated disease have poor outcomes with standard approaches. We previously reported that allogeneic stem cell transplantation (alloSCT) achieved durable remissions in MCL, however follow-up among patients with TP53-mutated disease was limited. Here we report extended follow-up of the overall cohort (n = 36) and TP53-mutated subset (n = 13) (median follow-up 10.8 and 4.2 years, respectively). Estimated overall survival was 56% at 10 years for the overall cohort and 59% at 4 years for the TP53-mutated subset. Among patients with TP53-mutated disease, no relapses occurred beyond 6 months post-transplant. Survival after post-alloSCT disease relapse was poor (median 2.1 years). These data confirm that alloSCT can be curative in MCL, including patients with TP53-mutated disease, and should be considered for earlier utilization in this subgroup for whom conventional chemoimmunotherapy is ineffective.
PICO Summary
Population
Retrospective cohort of adults who received allogeneic HSCT for mantle cell lymphoma and available for extended follow-up, from a single centre in Australia, (n=36)
Intervention
Allogeneic HSCT (TP53-mutated subset, n=13)
Comparison
Allogeneic HSCT (Overall cohort, n=36)
Outcome
Estimated overall survival was 56% at 10 years for the overall cohort and 59% at 4 years for the TP53-mutated subset. Among patients with TP53-mutated disease, no relapses occurred beyond 6 months post-transplant. Survival after post-alloSCT disease relapse was poor (median 2.1 years).
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5.
Long-Term Survivors After Failure of CAR-T Cell Therapy for Large B-Cell Lymphoma: A Role for Allogeneic Hematopoietic Cell Transplantation? A GLA/DRST Analysis
Derigs, P., Bethge, W. A., Krämer, I., Holtick, U., von Tresckow, B., Ayuk, F., Penack, O., Vucinic, V., von Bonin, M., Baldus, C., et al
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND The outcome of patients with large B-cell lymphoma (LBCL) who relapse or progress after CD19-directed CAR-T cell therapy administered as salvage therapy beyond the second treatment line is poor. However, a minority of patients become long-term survivors despite CAR-T failure. The German Lymphoma Alliance (GLA) has proposed a hierarchical management algorithm for CAR-T failure in LBCL, aiming at allogeneic hematopoietic cell transplantation (alloHCT) as definite therapy in eligible patients. PURPOSE The purpose of this study was to investigate characteristics, relapse patterns and management strategies in long-term survivors after CAR-T failure with particular focus on feasibility and outcome of alloHCT. STUDY DESIGN Retrospective analysis of all evaluable patients with relapse/progression event (REL) observed in a previous reported GLA sample (Bethge et al, Blood 2022) between November 2018 and May 2021. RESULTS REL occurred in 214 of 356 patients (60%) having undergone CAR-T for LBCL in the previous GLA study. For 143 of these 214 patients (67%) an evaluable dataset was available. 26 of 143 patients (18%) survived 12 months or longer from REL, 109 (76%) died within the first year after REL, and 8 patients (6%) were alive but had not reached the 12-months landmark. Long-term survivors had more favorable pre-CAR-T features, had a longer interval between CAR-T and REL, and had more often received a tumor biopsy post CAR-T failure, whereas the choice of the first salvage regimen had no impact. AlloHCT was feasible in 40 of 53 patients (75%) intended and resulted in a 12-month post-transplant overall survival of 36% in those patients who underwent transplant with sensitive or untreated REL. CONCLUSIONS AlloHCT after CAR-T failure in LBCL is feasible and may be an important contributor to long-term survival although selection bias has to be taken into account. Thus, alloHCT should be considered as a reasonable treatment option in eligible patients in this setting. Since the overall outlook after CAR-T failure nevertheless remains poor, novel effective therapeutic approaches are needed, either for allowing long-term disease control per se, or for improving the preconditions for successful alloHCT.
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Allogeneic hematopoetic stem cell transplant for patients with refractory T-Cell lymphomas
Massoud, R., Naim, H., Klyuchnikov, E., Janson, D., Wolschke, C., Ayuk, F., Kröger, N.
European journal of haematology. 2023
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Editor's Choice
Abstract
OBJECTIVE Allogeneic stem cell transplantation (allo-SCT) may have a curative potential due to the graft versus lymphoma effect. In this study, we aimed to compare transplant outcomes between refractory-T-NHL (ref-NHL) and Chemosensitive-T-NHL (CS-T-NHL). MATERIALS AND METHODS We retrospectively reviewed the records of 26 ref-NHL and 29 CS-T-NHL consecutive patients who underwent allo-SCT at our center and compared the transplant outcomes between the groups. RESULTS All patients were heavily pretreated with 27% of patients relapsing post-auto-SCT and two patients in the ref-T-NHL post-allo-SCT. Patients were transplanted mainly from unrelated donors. There were no differences in leucocytes and platelet engraftment between the two groups. At 3 years, the relapse incidence was 34% in Ref-TNHL and 19% in CS-TNHL (p = .33), with non-relapse mortality rates of 28% and 22%, respectively (p = .52). Female patients and those with a previous auto-SCT had lower relapse incidence (p = .045, p = .003). The 3-year overall survival was 39% in Ref-TNHL and 56% in CS-TNHL (p = .15). Trends for improved progression-free survival (PFS) and graft-versus-host disease relapse-free survival (GRFS) were observed in the CS-TNHL group (PFS: 60% vs. 30%, p = .075; GRFS 38% vs. 21%, p = .1). CONCLUSION Acknowledging the retrospective nature of our study, our results indicate that allo-SCT has a curative potential in patients with T-NHL even in refractory status.
PICO Summary
Population
Adults with lymphoma undergoing allogeneic transplant, from a single centre in Germany (n=55)
Intervention
patients with refractory T-cell lymphoma (ref-NHL, n=26)
Comparison
patients with chemosensitive T-cell lymphoma (CS-T-NHL, n=29)
Outcome
All patients were heavily pretreated with 27% of patients relapsing post-auto-SCT and two patients in the ref-T-NHL post-allo-SCT. Patients were transplanted mainly from unrelated donors. There were no differences in leucocytes and platelet engraftment between the two groups. At 3 years, the relapse incidence was 34% in Ref-TNHL and 19% in CS-TNHL, with non-relapse mortality rates of 28% and 22%, respectively. Female patients and those with a previous auto-SCT had lower relapse incidence. The 3-year overall survival was 39% in Ref-TNHL and 56% in CS-TNHL. Trends for improved progression-free survival (PFS) and graft-versus-host disease relapse-free survival (GRFS) were observed in the CS-TNHL group (PFS: 60% vs. 30%; GRFS: 38% vs. 21%).
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7.
Allogeneic hematopoietic stem cell transplantation for B-cell lymphoma in Taiwan
Lee, C. H., Lin, T. C., Yao, M., Hsiao, L. T., Ko, B. S., Liu, C. J., Chen, T. Y.
Cancer medicine. 2023
Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered for patients with high-risk B-cell lymphoma and relapsed or refractory disease. This study aimed to analyze the long-term follow-up data of patients who underwent allo-HSCT in Taiwan. This was a retrospective observational study using data from the Taiwan Society of Blood and Marrow Transplantation database. A total of 105 patients who underwent allo-HSCT because of high-risk, relapsed, or refractory disease between 2010 and 2019 were included. Forty-five percent of the patients previously underwent autologous stem cell transplantation (ASCT). The median follow-up duration was 18.6 months. The probability of 3-year progression-free survival and overall survival (OS) was 34.5% and 37%, respectively. The probability of 1-year non-relapse mortality was 31.4%, and the major cause was infection (75.8%). The multivariable analysis showed that not in remission at the time of transplantation and the absence of graft-versus-host disease (GVHD) were factors associated with inferior OS. The probability of 3-year OS in patients with diffuse large B-cell lymphoma who underwent allo-HSCT and allo-HSCT after ASCT was 40.2% and 25.2%, respectively. Allo-HSCT could be a salvage therapeutic option for relapsed or refractory B-cell lymphoma. Complete remission at the time of allo-HSCT and the presence of GVHD are independent variables for overall survival.
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The salvage role of allogeneic hematopoietic stem-cell transplantation in relapsed/refractory diffuse large B cell lymphoma
Min, G. J., Jeon, Y. W., Kim, T. Y., Kwag, D., Kim, B. S., Lee, J., Lee, J. H., Park, S. S., Park, S., Yoon, J. H., et al
Scientific reports. 2023;13(1):17496
Abstract
To clarify the role of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) in the chimeric antigen receptor T-cell therapy era, we analyzed the clinical characteristics and outcomes of 52 patients treated with allo-HSCT with relapsed/refractory diffuse large B cell lymphoma. Most enrolled patients had previously undergone intensive treatments, the median number of chemotherapy lines was 4, and the median time from diagnosis to allo-HSCT was 27.1 months. Patients were divided into remission-achieved (n = 30) and active-disease (n = 22) groups before allo-HSCT. Over a median follow-up period of 38.3 months, overall survival (OS) and event-free survival (EFS) rates were 38.4% and 30.6%, respectively. The cumulative incidence of relapse (CIR) and the non-relapsed mortality (NRM) were 36.7% and 32.7%, respectively. OS, EFS, and graft-versus-host disease-free, relapse-free survival (GRFS) outcomes were significantly superior in the remission-achieved group with lower CIR. In a multivariate analysis, a shorter interval from diagnosis to allo-HSCT reflected relatively rapid disease progression and showed significantly poor OS and EFS with higher CIR. Patients with active disease had significantly lower EFS, GRFS, and higher CIR. Previous autologous stem-cell transplantation was associated with better GRFS. Allo-HSCT is an established modality with a prominent group of cured patients and still has a role in the CAR T-cell era, particularly given its acceptable clinical outcomes in young patients with chemo-susceptible disease.
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Allogeneic stem cell transplant for treatment of mycosis fungoides and Sezary syndrome: a systematic review and meta-analysis
Goyal, A., O'Leary, D., Foss, F.
Bone marrow transplantation. 2023
Abstract
Allogeneic hematopoietic stem cell transplant (allo-HSCT) has been noted to be a potential curative treatment in cases of advanced-stage mycosis fungoides (MF) or Sezary syndrome (SS). To assess outcomes of allo-HSCT for MF/SS we performed a systematic review and meta-analysis including 15 manuscripts and 557 patients, published from 2010-2023. Meta-analysis revealed 1-year and 3+year overall survival (OS) of 51% (95% CI 39-64%) and 40% (32-49%). Progression-free survival at 1 year and 3+years were 42% (31-53%) and 33% (25-42%). Non-relapse mortality was 18% (13-23%). Relapse occurred in of 47% (40-53%) with a median time to relapse of 7.9 months (range 1.6-24 months). Rates of acute and chronic graft-versus-host disease (GVHD) were 45% (35-55%) and 40% (33-48%). Reduced-intensity conditioning (RIC) was associated with superior OS compared to myeloablative conditioning (MAC) (58% vs. 30%, p < 0.001). Of patients with relapse after allo-HSCT, 46% treated with donor lymphocyte infusion (DLI) achieved complete remission. These data support use of allo-HSCT for treatment of advanced-stage MF/SS and suggest superiority of RIC over MAC. Rates of GVHD were comparable to allo-HSCT in general. The improved OS for RIC and high rate of CR with DLI underscore the importance of the graft-versus-lymphoma effect in allo-HSCT for MF/SS.
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10.
Reduced Intensity Compared to Non-myeloablative Conditioning in Patients with Non-Hodgkin Lymphoma undergoing Allogeneic Hematopoietic Stem Cell Transplantation
Nath, K., Peterson, K., Brown, S., Devlin, S., Rodriguez, N., Barker, J., Giralt, S., Gyurkocza, B., Jakubowski, A., Papadopoulos, E., et al
Transplantation and cellular therapy. 2023
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Full text
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Editor's Choice
Abstract
BACKGROUND . Reduced intensity (RIC) and non-myeloablative (NMA) conditioning are preferred for patients with non-Hodgkin lymphoma (NHL) receiving allogeneic hematopoietic stem cell transplantation (allo-HCT). Although prior studies have suggested that higher-intensity regimens within RIC-NMA conditioning are associated with inferior outcomes in patients with NHL, the optimal conditioning regimen remains unknown. OBJECTIVES AND STUDY DESIGN . We performed a retrospective single-center analysis to determine outcomes of adult patients with B- and T-cell NHL who underwent allo-HCT and received either RIC or NMA conditioning between March 2008 - December 2019. RIC regimens included fludarabine-cyclophosphamide-thiotepa-4Gy-total body irradiation (Flu-Cy-TT-4Gy-TBI), fludarabine-melphalan (Flu-Mel), fludarabine-cyclophosphamide-4Gy-total body irradiation (Flu-Cy-4Gy-TBI) and fludarabine-busulfan-4 (Flu-Bu-4). The NMA regimen included fludarabine-cyclophosphamide-2Gy-total body irradiation (Flu-Cy-2Gy-TBI). The primary outcome was overall survival. Secondary outcomes included progression-free survival, non-relapse mortality and the incidence of acute and chronic graft-vs-host-disease (GvHD). RESULTS . Of 279 transplanted patients (median age, 58 years), 110 received RIC (55% Flu-Mel, 38% Flu-Cy-TT-4Gy-TBI, 6% Flu-Bu-4, 1% Flu-Cy-4Gy-TBI) and 169 received NMA conditioning with Flu-Cy-2Gy-TBI. With a median of 64 months of follow-up from allo-HCT, there was no significant difference in overall survival between the NMA and RIC groups (median not reached [NR] vs 103 months, respectively. P = 0.1), and this was maintained on multivariable analysis. Similarly, after adjustment for all independently significant covariates (age, Karnofsky performance status, HCT-CI, disease histology), the regression analysis showed no significant difference in progression-free survival with RIC compared to NMA conditioning (hazard ratio [HR] 1.38; 95% CI 0.92 - 2.09, P = 0.24). On univariable analysis, there was no significant difference in non-relapse mortality between RIC and NMA conditioning (100-day estimates: 10.0% vs. 1.8%, respectively, P = 0.5). After adjustment for age, ethnicity, Karnofsky performance score, HCT-CI, GvHD prophylaxis and donor source, RIC conditioning was associated with a significantly higher incidence of non-relapse mortality compared to NMA conditioning (HR 2.61, 95% CI 1.04 - 6.52, P = 0.039). On multivariable analysis, compared with the Flu-Cy-2Gy-TBI regimen, the RIC cohort had higher rates of grade II-IV (HR, 2.25; 95% CI, 1.31 - 3.86; P = 0.002) and grade III-IV acute GvHD (HR, 5.62; 95% CI, 2.03 - 15.6; P < 0.001). CONCLUSION . The findings of this study suggest that NMA conditioning with Flu-Cy-TBI-2Gy may be considered over more intensive RIC regimens for patients with NHL undergoing allo-HCT.
PICO Summary
Population
Adults with B- or T-cell non-Hodgkin lymphoma who underwent allogeneic stem cell transplant (allo-HSCT) at a single centre in USA (n=279)
Intervention
Reduced intensity conditioning (RIC) with or without total body irradiation (n=110)
Comparison
Non-myeloablative (NMA) conditioning (n=169)
Outcome
With a median of 64 months of follow-up from allo-HCT, there was no significant difference in overall survival between the NMA and RIC groups (median not reached [NR] vs 103 months, respectively), and this was maintained on multivariable analysis. Similarly, after adjustment for all independently significant covariates (age, Karnofsky performance status, HCT-CI, disease histology), the regression analysis showed no significant difference in progression-free survival with RIC compared to NMA conditioning (hazard ratio [HR] 1.38; 95% CI 0.92 - 2.09). On univariable analysis, there was no significant difference in non-relapse mortality between RIC and NMA conditioning (100-day estimates: 10.0% vs. 1.8%, respectively). After adjustment for age, ethnicity, Karnofsky performance score, HCT-CI, GvHD prophylaxis and donor source, RIC conditioning was associated with a significantly higher incidence of non-relapse mortality compared to NMA conditioning (HR 2.61, 95% CI 1.04 - 6.52). On multivariable analysis, compared with the Flu-Cy-2Gy-TBI regimen, the RIC cohort had higher rates of grade II-IV (HR, 2.25; 95% CI, 1.31 - 3.86) and grade III-IV acute GvHD (HR, 5.62; 95% CI, 2.03 - 15.6).