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

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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.

Original languageEnglish (US)
Pages (from-to)2115-2122
Number of pages8
JournalBiology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
Volume21
Issue number12
DOIs
StatePublished - Dec 1 2015

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Donor Selection
Homologous Transplantation
B-Cell Lymphoma
Bone Marrow Transplantation
Transplantation
Disease-Free Survival
Graft vs Host Disease
Tissue Donors
Fc Receptors
Bone Marrow
Blood Donors
Transplants
Recurrence
Cyclophosphamide
Survival
Mortality
Rituximab
Infection

Keywords

  • Allogeneic bone marrow transplantation
  • Donor prioritization
  • Fc receptor polymorphism
  • Haploidentical
  • Post-transplantation cyclophosphamide
  • Post-transplantation rituximab

ASJC Scopus subject areas

  • Transplantation
  • Hematology

Cite this

@article{89d78bf1a05f45d292aec8af22e15aa7,
title = "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",
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",
author = "Kanakry, {Jennifer A.} and Christopher Gocke and {Bolanos Meade}, {F Javier} and Douglas Gladstone and Lode Swinnen and Blackford, {Amanda L.} and Fuchs, {Ephraim J} and Huff, {Carol Ann} and Borrello, {Ivan M} and Matsui, {William H.} and Brodsky, {Robert A} and Gary Rosner and Shanbhag, {Satish P} and Leo Luznik and Jones, {Richard J} and Ambinder, {Richard F} and Kasamon, {Yvette L.}",
year = "2015",
month = "12",
day = "1",
doi = "10.1016/j.bbmt.2015.07.012",
language = "English (US)",
volume = "21",
pages = "2115--2122",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",
number = "12",

}

TY - JOUR

T1 - 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

AU - Kanakry, Jennifer A.

AU - Gocke, Christopher

AU - Bolanos Meade, F Javier

AU - Gladstone, Douglas

AU - Swinnen, Lode

AU - Blackford, Amanda L.

AU - Fuchs, Ephraim J

AU - Huff, Carol Ann

AU - Borrello, Ivan M

AU - Matsui, William H.

AU - Brodsky, Robert A

AU - Rosner, Gary

AU - Shanbhag, Satish P

AU - Luznik, Leo

AU - Jones, Richard J

AU - Ambinder, Richard F

AU - Kasamon, Yvette L.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - 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.

AB - 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.

KW - Allogeneic bone marrow transplantation

KW - Donor prioritization

KW - Fc receptor polymorphism

KW - Haploidentical

KW - Post-transplantation cyclophosphamide

KW - Post-transplantation rituximab

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U2 - 10.1016/j.bbmt.2015.07.012

DO - 10.1016/j.bbmt.2015.07.012

M3 - Article

C2 - 26183076

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VL - 21

SP - 2115

EP - 2122

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

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ER -