Immunoglobulin G Fc receptor FcgammaRIIIa 158 V/F polymorphism correlates with rituximab-induced neutropenia after autologous transplantation in patients with non-Hodgkin's lymphoma.
OBJECTIVE
Rituximab has been given after autologous hematopoietic cell transplantation for recurrent or refractory B-cell lymphoma with the goal of eradicating minimal residual disease. Our previous report showed that administration of two courses of rituximab after transplantation is feasible, with encouraging clinical outcomes after a short follow-up. However, neutropenia after the first or second post-transplantation rituximab treatment occurred in 52% of patients. We previously reported that polymorphisms of two immunoglobulin G Fc receptors predict rituximab response, presumably because of their role in antibody-dependent cellular cytotoxicity. In the current report, we determine whether FcgammaR polymorphisms are correlated with clinical outcomes in 33 patients with B-cell non-Hodgkin's lymphoma who received post-transplantation rituximab.


METHODS
Genomic DNA was used for FcgammaRIIIa V/F or the FcgammaRIIa H/R genotyping. The FcgammaR polymorphisms were then correlated with the incidence of rituximab-induced neutropenia, event-free survival (EFS), and overall survival (OS).


RESULTS
The FcgammaRIIIa 158 V allele dose was correlated with a higher incidence of rituximab-induced neutropenia. The odds of neutropenia after the first or second post-transplantation rituximab increased three-fold with each V allele (robust z = 2.08, P = .038). The FcgammaRIIa polymorphism had no impact on rituximab-induced neutropenia. We did not observe a correlation of either FcgammaRIIIa or FcgammaRIIa polymorphism with EFS or OS.


CONCLUSIONS
The high affinity FcgammaRIIIa 158 V allele is associated with rituximab-induced neutropenia after autologous transplantation. This is a potential tool to identify a high-risk population for developing neutropenia after antibody therapy.
Weng
Wen-Kai
WK
Division of Blood and Marrow Transplantation, 300 Pasteur Dr, Rm H3249, Stanford University School of Medicine, Stanford, CA 94305, USA. wkweng@stanford.edu
Negrin
Robert S
RS
Lavori
Philip
P
Horning
Sandra J
SJ
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D058846:Antibodies, Monoclonal, Murine-Derived; D003131:Combined Modality Therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced* / Q000235:genetics*; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics*; D012008:Recurrence; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C496124:FCGR3A protein, human; D017452:Receptors, IgG; D000069283:Rituximab