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Conditioning regimens for allotransplants for diffuse large B-cell lymphoma: myeloablative or reduced intensity?

ABSTRACT: The best conditioning regimen before allogeneic transplantation for high-risk diffuse large B-cell lymphoma (DLBCL) remains to be clarified. We analyzed data from 396 recipients of allotransplants for DLBCL receiving myeloablative (MAC; n = 165), reduced intensity (RIC; n = 143), or nonmyeloablative conditioning (NMAC; n = 88) regimens. Acute and chronic GVHD rates were similar across the groups. Five-year nonrelapse mortality (NRM) was higher in MAC than RIC and NMAC (56% vs 47% vs 36%; P = .007). Five-year relapse/progression was lower in MAC than in RIC/NMAC (26% vs 38% vs 40%; P = .031). Five-year progression-free survival (15%-25%) and overall survival (18%-26%) did not differ significantly between the cohorts. In multivariate analysis, NMAC and more recent transplant year were associated with lower NRM, whereas a lower Karnofsky performance score (< 90), prior relapse resistant to therapy, and use of unrelated donors were associated with higher NRM. NMAC transplants, no prior use of rituximab, and prior relapse resistant to therapy were associated with a greater risk of relapse/progression. In conclusion, allotransplantation with RIC or NMAC induces long-term progression-free survival in selected DLBCL patients with a lower risk of NRM but with higher risk of lymphoma progression or relapse.

SUBMITTER: Bacher U

PROVIDER: S-EPMC3501720 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Conditioning regimens for allotransplants for diffuse large B-cell lymphoma: myeloablative or reduced intensity?

Bacher Ulrike U Klyuchnikov Evgeny E Le-Rademacher Jennifer J Carreras Jeanette J Armand Philippe P Bishop Michael R MR Bredeson Christopher N CN Cairo Mitchell S MS Fenske Timothy S TS Freytes Cesar O CO Gale Robert Peter RP Gibson John J Isola Luis M LM Inwards David J DJ Laport Ginna G GG Lazarus Hillard M HM Maziarz Richard T RT Wiernik Peter H PH Schouten Harry C HC Slavin Shimon S Smith Sonali M SM Vose Julie M JM Waller Edmund K EK Hari Parameswaran N PN

Blood 20120924 20

The best conditioning regimen before allogeneic transplantation for high-risk diffuse large B-cell lymphoma (DLBCL) remains to be clarified. We analyzed data from 396 recipients of allotransplants for DLBCL receiving myeloablative (MAC; n = 165), reduced intensity (RIC; n = 143), or nonmyeloablative conditioning (NMAC; n = 88) regimens. Acute and chronic GVHD rates were similar across the groups. Five-year nonrelapse mortality (NRM) was higher in MAC than RIC and NMAC (56% vs 47% vs 36%; P = .00 ...[more]

PMID: 23007405

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Project description:Reduced-intensity conditioning (RIC) regimens are frequently used for allogeneic hematopoietic cell transplantation (allo-HCT) in patients with diffuse large B cell lymphoma (DLBCL). However, the RIC regimen with the best risk/benefit profile for allo-HCT in DLBCL is not known. This is particularly important because patients with DLBCL undergoing allo-HCT in the future would be enriched for those whose lymphoma has failed chimeric antigen receptor T cell (CAR-T) therapy or other novel immunotherapies, with potentially more advanced disease and suboptimal performance scores. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we report the outcomes of the 3 most commonly used allo-HCT RIC regimens in patients with DLBCL. Our analysis included a total of 562 adult DLBCL patients in the CIBMTR registry undergoing allo-HCT using matched related or unrelated donors, between 2008 and 2016. Patients received 1 of 3 RIC regimens: fludarabine/i.v. busulfan ~6.4 mg/kg (Flu/Bu), fludarabine/melphalan 140 mg/m2 (Flu/Mel140), or BCNU/etoposide/cytarabine/melphalan (BEAM). Accordingly, the study group was divided into 3 groups: Flu/Bu (n = 151), Flu/Mel140 (n = 296), and BEAM (n = 115). Relative to Flu/Bu, the Flu/Mel140 (hazard ratio [HR], 2.33; 95% confidence interval [CI], 1.42 to 3.82; P = .001) and BEAM (HR, 2.54; 95% CI, 1.34 to 4.80; P = .004) regimens were associated with a risk of higher nonrelapse mortality (NRM). Although the risk of relapse with Flu/Mel140 was lower than that with Flu/Bu (HR, .70; 95% CI, .52 to .95; P = .02), this did not translate to improved progression-free survival (HR, 1.04) or overall survival (HR, 1.30). There was a significantly higher risk of grade III-IV acute graft-versus-host disease with BEAM compared with Flu/Bu (HR, 2.19; 95% CI, 1.10 to 4.35; P = .03). In the chemosensitive subset, multivariate analysis showed a significantly higher mortality risk with Flu/Mel140 (HR, 1.48; 95% CI, 1.07 to 2.04; P = .02) relative to Flu/Bu conditioning. In the largest analysis comparing the impact of various RIC regimens on the survival of DLBCL patients undergoing allo-HCT, our results suggest that Flu/Bu is a better RIC choice in less fit or heavily pretreated patients due to lowest NRM risk.

Project description:ImportanceReduced-intensity conditioning and nonmyeloablative conditioning (RIC-NMAC) regimens are frequently used in allogeneic hematopoietic cell transplant (HCT) for non-Hodgkin lymphoma. However, the optimal RIC-NMAC regimen in allogeneic HCT for non-Hodgkin lymphoma is not known.ObjectiveTo investigate whether RIC-NMAC regimens at a higher end of the intensity spectrum are associated with increased nonrelapse mortality and lower overall survival compared with RIC-NMAC regimens at the lower end of the intensity spectrum in patients with non-Hodgkin lymphoma undergoing allogeneic HCT.Design, setting, and participantsThis cohort study used data from 1823 adult patients with non-Hodgkin lymphoma in the Center for International Blood and Marrow Transplant Research registry. Included patients underwent allogeneic HCT using matched related or unrelated donors between January 2008 and December 2016. Statistical analysis was performed from June 1, 2019, to February 10, 2020.InterventionsPatients received 1 of 4 RIC-NMAC regimens: fludarabine-intravenous busulfan (Flu-Bu), approximately 6.4 mg/kg (n = 458); fludarabine-melphalan (Flu-Mel140), 140 mg/m2 (n = 885); fludarabine-cyclophosphamide (Flu-Cy) (n = 391); or Flu-Cy with 2 Gy total body irradiation (Flu-Cy-2GyTBI) (n = 89).Main outcomes and measuresThe primary outcome was overall survival. Secondary outcomes were nonrelapse mortality, incidence of relapse, progression-free survival, and the incidence of acute and chronic graft-vs-host disease (GVHD).ResultsOf 1823 patients, 1186 (65%) were male, with a mean (SD) age of 54.8 (9.9) years. The 4-year adjusted OS was 58% in the Flu-Bu cohort, 67% in the Flu-Cy-2GyTBI cohort, 49% in the Flu-Mel140 cohort, and 63% in the Flu-Cy cohort (P < .001). After adjustment for age, Karnofsky performance score, HCT comorbidity index, NHL subtype, remission status at HCT, and the use of antithymocyte globulin or alemtuzumab, the regression analysis showed a significantly higher mortality risk associated with Flu-Mel140 compared with Flu-Bu (hazard ratio [HR], 1.34; 95% CI, 1.13-1.59; P < .001). Compared with the Flu-Cy cohort, the Flu-Mel140 cohort had a higher risk of chronic GVHD (HR, 1.38; 95% CI, 1.15-1.65; P < .001). The Flu-Mel140 regimen was associated with a higher nonrelapse mortality risk (HR, 1.78; 95% CI, 1.37-2.31; P < .001) compared with the Flu-Bu regimen.Conclusions and relevanceThe findings suggest that use of the more intense RIC-NMAC regimen, Flu-Mel140, may have a negative association with overall survival and may be associated with higher nonrelapse mortality. The Flu-Bu and Flu-Cy regimens with or without 2GyTBI regimens appeared to provide comparable overall survival.

Dataset Information

Conditioning regimens for allotransplants for diffuse large B-cell lymphoma: myeloablative or reduced intensity?

Publications

Conditioning regimens for allotransplants for diffuse large B-cell lymphoma: myeloablative or reduced intensity?

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