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Homozygous FCGR3A ‐158 V alleles predispose to late onset neutropenia after CHOP‐R for diffuse large B ‐cell lymphoma
Author(s) -
Keane C.,
Nourse J. P.,
Crooks P.,
NguyenVan D.,
Mutsando H.,
Mollee P.,
Lea R. A.,
Gandhi M. K.
Publication year - 2012
Publication title -
internal medicine journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.596
H-Index - 70
eISSN - 1445-5994
pISSN - 1444-0903
DOI - 10.1111/j.1445-5994.2011.02587.x
Subject(s) - medicine , genotype , lymphoma , chop , rituximab , neutropenia , vincristine , cyclophosphamide , oncology , gastroenterology , immunology , chemotherapy , genetics , gene , biology
Background Recent reports suggest genetic polymorphisms influence susceptibility to rituximab‐induced late‐onset neutropenia ( LON ), which in turn may be a predictor of good outcome in B ‐cell lymphoma. Aims We report the largest study to date assessing FCGR3A ‐ V158F polymorphisms in diffuse large B ‐cell lymphoma ( DLBCL ) treated with cyclophosphamide/hydroxydaunorubicin/ O ncovin (vincristine)/prednisone/rituximab ( CHOP ‐ R ). The influence of C1qA ‐ A276G polymorphisms in DLBCL , and the impact of both polymorphisms on susceptibility to LON and outcome were also examined. Methods 115 DLBCL patients treated with CHOP ‐R were compared with 105 healthy W hite people controls with regards to FCGR3A ‐ V158F and C1qA ‐ A276G polymorphisms. LON incidence and event‐free and overall survival ( EFS and OS ) were analysed for linkage to either polymorphism. Results The FCGR3A ‐ V158F but not the C1qA ‐ A276G polymorphism influenced the risk of developing LON . 50% of FCGR3A ‐158 V / V patients experienced LON . In contrast, only 7% V / F and 2% F / F experienced LON . The FCGR3A ‐158 V / V genotype was associated with LON compared with V / F ( P = 0.028) and F / F genotypes ( P = 0.005). Although no patients with either LON or FCGR3A ‐158 V homozygosity relapsed compared with 33% FCGR3A‐158F/ F and 21% non‐ LON , this did not translate into improved EFS or OS . Conclusions Polymorphic analysis may be a predictive tool to identify those at high risk of LON . Prospective studies are required to establish definitively if LON or FCGR3A ‐158 V / V genotype influences outcome.