-
1.
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.
-
2.
Allogeneic hematopoietic stem cell transplantation from unmanipulated haploidentical donor and unrelated cord blood for T-cell lymphoma: a retrospective study from the Société Francophone de Greffe de Moelle et de Therapie Cellulaire
Cornillon, J., Daguenet, E., Tournilhac, O., Blaise, D., N. Guyen S, Wallet, H. L., Chevallier, P., Dulery, R., Forcade, E., Srour, M., et al
Bone marrow transplantation. 2021
Abstract
After chemotherapy, fewer than 30% of patients with T-cell lymphoma (T-NHL) are long-term disease-free survivors. Thus, there is a growing interest in allogeneic stem cell transplantation (alloSCT) and its potential graft-versus-lymphoma effect (GVL) for patient with high-risk or recurrent T-NHL with the aim at providing durable disease control in T-NHL. We conducted this registry study to evaluate the outcome of recipients of alternative donor alloSCT for T-NHL. Patients transplanted with Haploidentical donor (Haplo, n?=?41) or Umbilical Cord Blood (UCB, n?=?54) were analyzed for overall survival (OS), non-relapse mortality (NRM), relapse, and acute/chronic graft-versus-host disease (aGVHD/cGVHD) incidence. At 2 years, OS and PFS were, respectively, of 59% and 53%, without significant difference between Haplo and UCB. In multivariate analysis, disease status at transplant was an independent risk factor for OS and PFS, and aGVHD III-IV was the main factor for OS and NRM. While no major impact of donor source on survival and mortality was noted, this study suggests that alternative donor transplantation appears feasible and offers benefits to patients with T-cell lymphoma.
-
3.
Outcome after Haematopoietic Stem Cell Transplantation in Patients with Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type: a French Study from the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)
Walter, L. P., Couronné, L., Jais, J. P., Nguyen, P. D., Blaise, D., Pigneux, A., Socié, G., Thieblemont, C., Bachy, E., Fegueux, N., et al
American journal of hematology. 2021
Abstract
We evaluated the outcome of 65 French patients with Extranodal NK/T-cell lymphoma, nasal type (ENKTL) undergoing haematopoietic stem cell transplantation (HSCT) (19 allogeneic and 46 autologous). Fifty-four patients (83%), most of which receiving L asparaginase (L-aspa) containing regimens (81%), achieved complete or partial response at time of HCST. After a median follow-up of 79.9 months, 4-years progression-free survival (PFS) and overall survival (OS) were similar in both autologous and allogeneic groups (PFS: 34% vs 26%, p=0.12 and OS: 52% vs 53%, p=0.74). Response status at HSCT was the major independent prognostic factor on survival (OS: HR: 4.013 [1.137; 14.16], p=0.031 and PFS: HR: 5.231 [1.625; 16.838], p=0.006). As compared to control patients receiving chemotherapy and/or radiotherapy containing regimens only, upfront HSCT did not improve the outcome of responder patients, including those treated by L-aspa. However, it tends to provide survival benefit for relapsed patients with initial high-risk clinical features who achieved second remission. Whereas the place of HSCT in upfront therapy has still to be clarified, these data confirm that HSCT should be considered for consolidation in selected patients with relapsed ENKTL. Based on a large non Asian ENKTL cohort since the L-aspa era, this study provides some insight into the survival patterns of ENKTL patients with HSCT in the Western hemisphere and may give future direction for the next clinical trial design. This article is protected by copyright. All rights reserved.
-
4.
Allogeneic stem cell transplantation for peripheral T cell lymphomas: a retrospective study in 285 patients from the Societe Francophone de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC)
Mamez, A. C., Dupont, A., Blaise, D., Chevallier, P., Forcade, E., Ceballos, P., Mohty, M., Suarez, F., Beguin, Y., Peffault De Latour, R., et al
Journal of hematology & oncology. 2020;13(1):56
Abstract
BACKGROUND Peripheral T cell lymphomas form a heterogeneous group with a usually dismal prognostic. The place of allogeneic stem cell transplantation to treat PTCL is debated. METHODS We retrospectively analyzed the overall survival (OS), event-free survival (EFS), relapse, and transplant-related mortality (TRM) and associated variables in 285 adults with non-primary cutaneous PTCL (PCTL-NOS (39%), angioimmunoblastic T cell lymphomas (29%), anaplastic T cell lymphomas (15%), and other subtypes (17%)), who received alloSCT in 34 centers between 2006 and 2014. RESULTS AlloSCT was given as part of front-line therapy (n = 138) to 93 patients in first complete response (CR) and 45 in first partial response (PR), and of salvage therapy (n = 147) to 116 patients for second or more CR/PR and 31 for progressive disease. Reduced-intensity conditioning (RIC) was given to 172 patients (62%), while 107 (38%) received myeloablative conditioning (MAC). The median follow-up was 72.4 months. The 2- and 4-year OS were 65% and 59%, respectively, and the cumulative incidence of relapse was 18% after 1 year and 19% after 2 years. TRM was 21% at 1 year, 24% after 2 years, and 28% after 4 years. In multivariate analysis, grade III-IV acute GvHD (HR = 2.57, 95% CI 1.53-4.31; p = 0.00036), low Karnofsky score < 80% (HR = 5.14, 95% CI 2.02-13.06; p = 0.00058), and progressive disease status before transplant (HR = 2.21, 95% CI 1.25-3.89; p = 0.0062) were significantly associated with a reduced OS. CONCLUSIONS The data demonstrate in the largest retrospective cohort of non-cutaneous PTCL so far reported that alloSCT after RIC or MAC is an effective strategy, even in chemoresistant patients.
-
5.
Idelalisib exposure before allogeneic stem cell transplantation in patients with follicular lymphoma: an EBMT survey
Sellner, L., Schetelig, J., Koster, L., Choi, G., Blaise, D., Beelen, D., Schianca, F. C., Passweg, J., Schanz, U., Gyan, E., et al
Bone marrow transplantation. 2020
-
6.
PTCy-based haploidentical vs matched related or unrelated donor reduced-intensity conditioning transplant for DLBCL
Dreger, P., Sureda, A., Ahn, K. W., Eapen, M., Litovich, C., Finel, H., Boumendil, A., Gopal, A., Herrera, A. F., Schmid, C., et al
Blood advances. 2019;3(3):360-369
-
-
Free full text
-
Abstract
This study retrospectively compared long-term outcomes of nonmyeloablative/reduced intensity conditioning (NMC/RIC) allogeneic hematopoietic cell transplantation (allo-HCT) from a haploidentical family donor (haplo-HCT) using posttransplant cyclophosphamide (PTCy) with those of matched sibling donor (MSD) and matched unrelated donor (MUD) with or without T-cell depletion (TCD+/TCD-) in patients with relapsed diffuse large B-cell lymphoma (DLBCL). Adult patients with DLBCL who had undergone their first NMC/RIC allo-HCT between 2008 and 2015 were included. Recipients of haplo-HCT were limited to those receiving graft-versus-host disease (GVHD) prophylaxis with PTCy. GVHD prophylaxis in MSD was limited to calcineurin inhibitor (CNI)-based approaches without in vivo TCD, while MUD recipients received CNI-based prophylaxis with or without TCD. Outcome analyses for overall survival (OS) and progression-free survival (PFS), nonrelapse mortality (NRM), and disease relapse/progression were calculated. A total of 1438 patients (haplo, 132; MSD, 525; MUD TCD+, 403; and MUD TCD-, 378) were included. Patients with haplo donors were significantly older, had a better performance status and had more frequently received total body irradiation-based conditioning regimens and bone marrow grafts than MSD and MUD TCD+ or TCD-. 3-year OS, PFS, NRM and relapse/progression incidence after haplo-HCT was 46%, 38%, 22%, and 41%, respectively, and not significantly different from outcomes of matched donor transplants on multivariate analyses. Haplo-HCT was associated with a lower cumulative incidence of chronic GVHD compared with MSD, MUD TCD+/TCD-. NMC/RIC haplo-HCT with PTCy seems to be a valuable alternative for patients with DLBCL considered for allo-HCT but lacking a matched donor.
-
7.
Outcome in patients with diffuse large B-cell lymphoma who relapse after autologous stem cell transplantation and receive active therapy. A retrospective analysis of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation (EBMT)
Gonzalez-Barca, E., Boumendil, A., Blaise, D., Trneny, M., Masszi, T., Finel, H., Michieli, M. G., Bittenbring, J. T., Gritti, G., Snowden, J. A., et al
Bone marrow transplantation. 2019
Abstract
Autologous hematopoietic stem cell transplantation (auto-HSCT) is the standard of care for patients with diffuse large B-cell lymphoma (DLBCL) who relapse/progress after first line chemoimmunotherapy. Long-term outcome of those who relapse after transplant is poor. We present the results of a retrospective study of 256 adult patients reported to the EBMT registry with DLBCL who relapsed after auto-HSCT performed between 2003 and 2013, and who received active salvage strategies. One hundred and fifty-four (60%) were male; median age was 53 years. Median time to relapse was 7 months, 65% relapsed during the first year. Overall response rate after salvage therapy was 46%. Median follow-up after first salvage therapy was 40 months (IQR 23-63 months). Overall survival (OS) at 3 years was 27% (95% CI 22-33). OS at 3 years of patients relapsing longer than 1 year after auto-HSCT was 41% (95% CI 31-53) compared with 20% (95% CI 14-24) in those who relapsed in less than 1 year. Eighty-two patients (32%) had a second HSCT, an allogeneic HSCT (allo-HSCT) in 69 cases, at a median time of 6.5 months after relapse. OS at 3 years after allo-HSCT was 36% (95% CI 25-51). In conclusion, the prognosis of patients with DLBCL that relapse after auto-HSCT is dismal. Patients who relapse in less than 1 year remain an unmet need, and should be considered for CAR T cell therapy or clinical trials. Patients who relapse after 1 year can be rescued with salvage therapies and a second HSCT. These results provide a benchmark to compare data of new prospective studies.
-
8.
The impact of advanced patient age on mortality after allogeneic hematopoietic Cell Transplantation for Non-Hodgkin's Lymphoma: A retrospective study by the EBMT Lymphoma Working Party
Kyriakou, C., Boumendil, A., Finel, H., N. NNorbert Schmitz, Andersen, N. S., Blaise, D., Chevallier, P., Browne, P., Malladi, R., Niederwieser, D., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
BACKGROUND More than 60% of patients with non-Hodgkin lymphoma (NHL) are over 60 years old at presentation. The purpose of this study was to compare the potential risks and benefits of allogeneic HSCT in elderly patients with NHL with younger patients in a large sample taking also into account comorbidity information. METHODS Eligible were all patients >=18 years who had received an alloHCT from a matched sibling or unrelated donor for NHL between 2003 and 2013 and were registered with the EBMT. Primary endpoint was 1-year non-relapse mortality (NRM). RESULTS 3,919 patients were eligible and categorized by age: young (Y), 18-50y (n=1,772); middle age (MA) 51-65y (n=1,967); old (O) 66-77y (n=180). Of the total 3,919 patients, 37% had FL, 30% DLBCL, 21 % MCL, and 11% PTCL; 85% were chemosensitive and 15% chemorefractory at the time of alloHCT, respectively. With a median follow-up for survivors of 4.5 years, NRM for Y/MA/O was 13%/20%/33% at 1 year (p <0.001) whilst relapse incidence and overall survival (OS) at 3 years were 30%/31%/28% (p=0.355) and 60%/54%/38% (p <0.001) for Y/MA/O, respectively. Multivariable adjustment for confounders including gender, NHL subset, time from diagnosis, chemosensitivity, donor, and conditioning confirmed that higher age was a significant predictor for NRM and OS but not for relapse risk. Although comorbidity was a significant predictor of NRM in a subset analysis restricted to the 979 patients with comorbidity information available, age retained its significant impact on NRM. CONCLUSIONS AlloHCT in patients >65y exerts similar NHL control as in younger patients but is associated with a higher NRM which is not fully explained by comorbidity. Thus, although alloHCT is feasible and effective in very old patients, the increased NRM risk has to be taken into account when deciding about transplant indication for NHL in this age group.
-
9.
Reduced-intensity versus reduced-toxicity myeloablative fludarabine/busulfan-based conditioning regimens for allografted non-Hodgkin lymphoma adult patients: a retrospective study on behalf of the Societe Francophone de Greffe de Moelle et de Therapie Cellulaire
Le Bourgeois, A., Labopin, M., Blaise, D., Ceballos, P., Vigouroux, S., Peffault de Latour, R., Marcais, A., Bulabois, C. E., Bay, J. O., Chantepie, S., et al
Annals of Oncology. 2017;28(9):2191-2198
Abstract
Background: Fludarabine/busulfan-based conditioning regimens are widely used to perform allogeneic stem-cell transplantation (allo-SCT) in high-risk non-Hodgkin lymphoma (NHL) patients. The impact of the dose intensity of busulfan on outcomes has not been reported yet. Patients and methods: This was a retrospective with the aim to compare the outcomes of NHL patients who received before allo-SCT a fludarabine/busulfan conditioning regimen, either of reduced intensity (FB2, 2 days of busulfan at 4mg/kg/day oral or 3.2mg/kg/day i.v.) (n=277) or at a myeloablative reduced-toxicity dose (FB3/FB4, 3 or 4 days of busulfan at 4mg/kg/day oral or 3.2mg/kg/day i.v.) (n=101). Results: In univariate analysis, the 2-year overall survival (FB266.5% versus 60.3%, P=0.33), lymphoma-free survival (FB257.9% versus 49.8%, P=0.26), and non-relapse mortality (FB219% versus 21.1%, P=0.91) were similar between both groups. Cumulative incidence of grade III-IV acute graft versus host disease (GVHD) (FB211.2% versus 18%, P=0.08), extensive chronic GVHD (FB2: 17.3% versus 10.7%, P=0.18) and 2-year GVHD free-relapse free survival (FB2: 44.4% versus 42.8%, P=0.38) were also comparable. In multivariate analysis there was a trend for a worse outcome using FB3/FB4 regimens (overall survival: HR 1.47, 95% CI: 0.96-2.24, P=0.08; lymphoma-free survival: HR: 1.43, 95% CI: 0.99-2.06, P=0.05; relapse incidence: HR 1.54; 95% CI: 0.96-2.48, P=0.07). These results were confirmed using a propensity score-matching strategy. Conclusion: We conclude that reduced toxicity myeloablative conditioning with fludarabine/busulfan does not improve the outcomes compared with reduced-intensity conditioning in adults receiving allo-SCT for NHL.
-
10.
Allogeneic stem cell transplantation for patients with mantle cell lymphoma who failed autologous stem cell transplantation: a national survey of the SFGM-TC
Tessoulin, B., Ceballos, P., Chevallier, P., Blaise, D., Tournilhac, O., Gauthier, J., Maillard, N., Tabrizi, R., Choquet, S., Carras, S., et al
Bone Marrow Transplantation. 2016;51(9):1184-90
Abstract
Poly-chemotherapy plus rituximab followed by autologous stem cell transplantation (auto-SCT) is standard care for untreated young patients with mantle cell lymphoma (MCL). Despite this intensive treatment, transplant patients remain highly susceptible to relapse over time. The French SFGM-TC performed a national survey on reduced-intensity conditioning allogeneic stem cell transplantation (RIC-allo-SCT) for fit relapsed/refractory patients who failed after auto-SCT (n=106). Median times of relapse after auto-SCT, and from auto-SCT to RIC-allo-SCT were 28 months and 3.6 years, respectively. Sixty per cent of patients received at least three lines of treatment before RIC-allo-SCT. Conditioning regimens for RIC-allo-SCT were heterogeneous. Twenty patients experienced grade III/IV aGvHD, extensive cGvHD was reported in 28 cases. Median follow-up after RIC-allo-SCT was 45 months. Median PFS after RIC-allo-SCT was 30.1 months and median overall survival was 62 months. Treatment-related mortality (TRM) at 1 year and 3 years were estimated at 28% and 32%, respectively. A total of 52 patients died; major causes of death were related to toxicity (n=34) and MCL (n=11). Patients in good response before RIC-allo-SCT experienced a better PFS and OS. Our work highlights the need for new RIC-allo-SCT MCL-tailored approaches to reduce TRM, and early and late relapse.