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1.
The conditional survival analysis of relapsed DLBCL after autologous transplant: a subgroup analysis of LY.12 and CORAL
Assouline, S., Li, S., Gisselbrecht, C., Fogarty, P., Hay, A., van den Neste, E., Shepherd, L. E., Schmitz, N., Baetz, T., Keating, A., et al
Blood advances. 2020;4(9):2011-2017
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Abstract
The conditional survival of patients after frontline therapy for diffuse large B-cell lymphoma (DLBCL) approaches that of the general population once patients have survived disease free for 2 years. We sought to determine the conditional survival of patients among patients with relapsed de novo DLBCL successfully undergoing an autologous stem-cell transplant (ASCT) after first relapse. A total of 478 patients with de novo DLBCL, relapsed after 1 treatment from the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) and LY.12, were included. Patients were followed prospectively after ASCT for a median of 5.3 and 8.2 years, respectively. Individual patient data were analyzed for event-free survival (EFS) and overall survival. Standardized mortality ratios (SMRs) were estimated using French and Canadian life tables. The EFS estimates declined with each year of follow-up after ASCT and were 50.1% (95% confidence interval [CI]: 43.7% to 56.3%) and 43.4% (95% CI: 36.7% to 49.9%) at 5 years in CORAL and LY.12, respectively. The rate of death stabilized once patients achieved at least 4 years of EFS. Compared with the age- and sex-matched population, the SMR was significantly higher until 5 years after ASCT, when values were no longer statistically significant. Patients undergoing ASCT for relapsed DLBCL continue to have a higher rate of death at least until they have survived event free for 5 years. These observations can help to determine endpoints for future clinical trials in this population and for patient counseling. This trial was registered at www.clinicaltrials.gov as #NCT00078949.
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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
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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
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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.
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Autologous stem cell transplantation for HIV-associated lymphoma in the antiretroviral and rituximab era: a retrospective study by the EBMT Lymphoma Working Party
Hubel, K., Re, A., Boumendil, A., Finel, H., Hentrich, M., Robinson, S., Wyen, C., Michieli, M., Kanfer, E., Diez-Martin, J. L., et al
Bone marrow transplantation. 2019
Abstract
The present study aimed at describing the outcome of patients with HIV-associated lymphomas following autologous hematopoietic stem cell transplantation (autoHCT) in the rituximab and combined antiretroviral therapy (cART) era. Eligible for this retrospective study were HIV-positive patients with lymphoma who received autoHCT between 2007 and 2013. A total of 118 patients were included with a median age of 45 years (range 24-66). Underlying diagnoses were diffuse large B cell lymphoma in 47%, Hodgkin lymphoma in 24%, Burkitt lymphoma in 18%, and plasmablastic lymphoma in 7% of patients. Disease status at autoHCT was complete remission in 44%, partial remission (PR) in 38%, and less than PR in 18% of the patients. With a median follow-up of 4 years, 3-year non-relapse mortality, incidence of relapse, progression-free survival (PFS) and overall survival (OS) were 10%, 27%, 63% and 66%, respectively. By multivariate analysis, disease status less than PR but not CD4+ cell count at the time of autoHCT was a significant predictor of unfavorable PFS and OS. In conclusion, in the era of cART and chemoimmunotherapy, the outcome of autoHCT for HIV-related lymphoma is driven by lymphoma-dependent risk factors rather than by characteristics of the HIV infection.
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Allogeneic hematopoietic stem cell transplantation for patients with relapsed/refractory systemic anaplastic large cell lymphoma. A retrospective analysis of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation
Domingo-Domenech, E., Boumendil, A., Climent, F., Socie, G., Kroschinsky, F., Finel, H., Vandenbergue, E., Nemet, D., Stelljes, M., Bittenbring, J. T., et al
Bone marrow transplantation. 2019
Abstract
Information regarding the curative role of allogeneic stem cell transplantation (allo-HCT) in systemic anaplastic large cell lymphoma (sALCL) is scarce. We analyzed the results of allo-HCT in patients with relapsed/refractory sALCL with special emphasis on the role of brentuximab vedotin (BV) as a bridge to allo-HCT. Forty-four patients (24 females, median age 38 years) with sALCL were included. Twenty-three patients (52%) received BV before allo-HCT; BV-treated patients were more heavily pretreated (≥3 lines of therapy in 74% vs. 38%, p = 0.04). Twenty-three patients (52%) were in complete remission (CR) at allo-HCT. Three-year nonrelapse mortality and incidence of relapse (IR) after allo-HCT were 7% and 40%, respectively. With a median follow-up of 39 (12-69) months for survivors, 3-year progression-free survival (PFS) and overall survival were 53% and 74%, respectively. Univariate analysis showed that heavily pretreated patients and those not in CR had a higher IR and a lower PFS. The use of BV before transplant did not impact on any of the outcomes. Allo-HCT is a curative therapeutic strategy in a significant proportion of patients with relapsed/refractory sALCL; BV does not seem to modify transplant-related outcomes but might be able to render more patients candidates for this curative treatment.
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Allogeneic stem cell transplantation as part of front line therapy for Mantle cell lymphoma
Rule, S., Cook, G., Russell, N. H., Hunter, A., Robinson, S., Morley, N., Sureda, A., Patrick, P., Clifton-Hadley, L., Adedayo, T., et al
British journal of haematology. 2018
Abstract
Mantle cell lymphoma (MCL) is an aggressive form of non-Hodgkin lymphoma that remains incurable for the majority of patients. Allogeneic stem cell transplantation (alloSCT) produces long-term disease-free remissions for around 30-40% patients, however it is reserved for the treatment of relapsed disease. This study examined the use of front line transplantation for young patients in an attempt to improve outcomes. Twenty-five patients received an alloSCT using BEAM [BCNU (carmustine), etoposide, cytarabine, melphalan)-Campath conditioning following permissive induction therapy from both related and unrelated donors. This was a multi-centre prospective trial. Twenty-four of 25 patients engrafted with no non-relapse mortality events by day 100. With a median follow-up of 60.5 months, there have been six deaths (3 from MCL). The progression-free survival (PFS) and overall survival were 68% and 80% at 2 years and 56% and 76% at 5 years. PFS was very similar for both sibling and unrelated transplants and there was no difference in PFS between patients with respect to remission status prior to transplantation. Nine (38%) patients experienced acute graft-versus-host disease (GVHD) and 14 (58%) experienced chronic GVHD, of which 8 were extensive. Front line alloSCT is feasible but should only be considered for patients at high risk of early progression following conventional therapy.
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Allogeneic hematopoietic stem cell transplantation for relapsed follicular lymphoma: A combined analysis on behalf of the Lymphoma Working Party of the EBMT and the Lymphoma Committee of the CIBMTR
Sureda, A., Zhang, M. J., Dreger, P., Carreras, J., Fenske, T., Finel, H., Schouten, H., Montoto, S., Robinson, S., Smith, S. M., et al
Cancer. 2018
Abstract
BACKGROUND Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains the only potentially curative treatment option for relapsed follicular lymphoma (FL), yet questions remain about the optimal timing. This study analyzed long-term outcomes and associated factors among recipients of allo-HCT with FL. METHODS Patients with relapsed FL who underwent allo-HCT from 2001 to 2011 with a human leukocyte antigen (HLA)-matched donor were included. Outcome analyses for overall survival (OS), progression-free survival (PFS), transplant-related mortality (TRM), and disease relapse/progression were calculated. A multivariate analysis was performed to determine factors associated with outcomes, and a prognostic score for treatment failure was developed in a subset analysis of patients. RESULTS In all, 1567 patients with relapsed FL were included; the median follow-up was 55 months. The 5-year probabilities of OS and PFS were 61% and 52%, respectively. The 5-year cumulative incidences of disease progression/relapse and TRM were 29% and 19%, respectively. Chemoresistant disease, older age, heavy pretreatment, poor performance status (PS), and myeloablative protocols were predictors for worse survival. The prognostic score, using age, lines of prior therapy, disease status, and PS, stratified patients into 3 groups-low, intermediate, and high risk-with 5-year PFS rates of 68%, 53%, and 46%, respectively, and 5-year OS rates of 80%, 62%, and 50%, respectively. CONCLUSIONS Allo-HCT should be considered for patients with relapsed FL and available HLA-matched donors. Outcomes are better in earlier phases of the disease, and reduced-intensity conditioning should be preferred. The prognostic score presented here can assist in counseling patients and determining the time to proceed to transplantation. Cancer 2018. (c) 2018 American Cancer Society.