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Clinical Trial
. 2015 Dec;21(12):2115-2122.
doi: 10.1016/j.bbmt.2015.07.012. Epub 2015 Jul 14.

Phase II Study of Nonmyeloablative Allogeneic Bone Marrow Transplantation for B Cell Lymphoma with Post-Transplantation Rituximab and Donor Selection Based First on Non-HLA Factors

Jennifer A Kanakry  1 , Christopher D Gocke  2 , Javier Bolaños-Meade  1 , Douglas E Gladstone  1 , Lode J Swinnen  1 , Amanda L Blackford  3 , Ephraim J Fuchs  1 , Carol Ann Huff  1 , Ivan Borrello  1 , William H Matsui  1 , Robert A Brodsky  1 , Gary L Rosner  3 , Satish Shanbhag  1 , Leo Luznik  1 , Richard J Jones  1 , Richard F Ambinder  4 , Yvette L Kasamon  1
Affiliations
Clinical Trial

Phase II Study of Nonmyeloablative Allogeneic Bone Marrow Transplantation for B Cell Lymphoma with Post-Transplantation Rituximab and Donor Selection Based First on Non-HLA Factors

Jennifer A Kanakry et al. Biol Blood Marrow Transplant. 2015 Dec.

Abstract

Outcomes of nonmyeloablative (NMA), HLA-haploidentical (haplo), related-donor allogeneic blood or marrow transplantation (allo-BMT) with high-dose post-transplantation cyclophosphamide (PTCy) appear to be similar to those using HLA-matched donors. Thus, it may be possible to prioritize donor factors other than HLA matching that could enhance antitumor activity. The Fc receptor polymorphism FCGR3A-158VV may confer greater sensitivity to rituximab than FCGR3A-158FF. In a prospective phase II study of NMA, related-donor allo-BMT with PTCy and post-transplantation rituximab for patients with B cell lymphomas, we hypothesized that donor selection that prioritized FCGR3A-158 polymorphism over HLA matching would be feasible, safe, and improve outcomes. The primary endpoint was 1-year progression-free survival (PFS). Of 83 patients transplanted (median age, 59 years), 69 (83%) received haplo grafts. Fifty-four (65%) received a graft that maintained or improved their Fc receptor polymorphism status. With 2.6-year median follow-up, the 1-year PFS and overall survival (OS) probabilities were 71% and 86%, respectively, with 1-year relapse and nonrelapse mortality (NRM) probabilities of 20% and 8%. At 1 year, the probability of acute grades II to IV graft-versus-host disease (GVHD) was 41%, with acute grades III to IV GVHD probability of 5% and chronic GVHD probability of 11%. Among haplo transplants, the 1-year probabilities of PFS, OS, relapse, and NRM were 70%, 83%, 20%, and 10%, respectively. No differences in outcomes were observed based on donor FCGR3A-158 polymorphism. Excess infection risk was not apparent with post-transplantation rituximab. Although donor selection based on FCGR3A-158 polymorphism was not shown to influence PFS, this study suggests that donor selection based on criteria other than best HLA match is feasible and safe. This study opens the way for the future investigation of donor prioritization based on promising non-HLA factors that may improve antitumor activity and decrease relapse after allo-BMT. This study was registered at www.clinicaltrials.gov as NCT00946023.

Keywords: Allogeneic bone marrow transplantation; Donor prioritization; Fc receptor polymorphism; Haploidentical; Post-transplantation cyclophosphamide; Post-transplantation rituximab.

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Figures

Figure 1
Figure 1. Overall outcomes of non-myeloablative, related-donor bone marrow transplantation with posttransplantation high-dose cyclophosphamide and rituximab (n=83)
A) Relapse and non-relapse mortality by competing risk analysis. B) Acute graft-versus-host disease (grades 2–4 and grades 3–4) by competing risk analysis. C) Chronic graft-versus-host disease (overall and requiring systemic therapy) by competing risk analysis. D) Progression-free and overall survival. Of these 83 patients, 69 received HLA-haploidentical grafts.
Figure 2
Figure 2. Outcomes of non-myeloablative, related-donor bone marrow transplantation according to donor FCGR3A-158 polymorphism
A) Relapse by competing-risk analysis. B) Progression-free survival.
Figure 3
Figure 3. Outcomes of non-myeloablative, related HLA-haploidentical donor bone marrow transplantation (n=69)
A) Relapse and non-relapse mortality by competing risk analysis. B) Progression-free and overall survival.
See this image and copyright information in PMC

References

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