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. 2010 Jan 10;28(2):279-84.
doi: 10.1200/JCO.2009.25.0274. Epub 2009 Nov 23.

Immunoglobulin G Fc receptor FcgammaRIIIa 158 V/F polymorphism correlates with rituximab-induced neutropenia after autologous transplantation in patients with non-Hodgkin's lymphoma

Wen-Kai Weng  1 , Robert S Negrin, Philip Lavori, Sandra J Horning
Affiliations

Immunoglobulin G Fc receptor FcgammaRIIIa 158 V/F polymorphism correlates with rituximab-induced neutropenia after autologous transplantation in patients with non-Hodgkin's lymphoma

Wen-Kai Weng et al. J Clin Oncol. .

Abstract

Purpose: 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.

Patients and 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.

Conclusion: 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.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
Kaplan-Meier estimates of event-free survival (EFS) and overall survival (OS).
See this image and copyright information in PMC

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