title: Homozygous FCGR3A-158V alleles predispose to late onset neutropenia after CHOP-R for diffuse large B-cell lymphoma.
abstract: 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.
  
  
  OBJECTIVE
  We report the largest study to date assessing FCGR3A-V158F polymorphisms in diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide/hydroxydaunorubicin/Oncovin (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 White 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-158V/V patients experienced LON. In contrast, only 7% V/F and 2% F/F experienced LON. The FCGR3A-158V/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-158V 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-158V/V genotype influences outcome.
authors: Haematology Department, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
authors: C
authors: C
authors: Keane
authors: J P
authors: JP
authors: Nourse
authors: P
authors: P
authors: Crooks
authors: D
authors: D
authors: Nguyen-Van
authors: H
authors: H
authors: Mutsando
authors: P
authors: P
authors: Mollee
authors: R A
authors: RA
authors: Lea
authors: M K
authors: MK
authors: Gandhi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D003520:Cyclophosphamide / Q000009:adverse effects; D004317:Doxorubicin / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006720:Homozygote; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000235:genetics*; D011241:Prednisone / Q000009:adverse effects; D011446:Prospective Studies; D017452:Receptors, IgG / Q000235:genetics*; D013997:Time Factors; D014750:Vincristine / Q000009:adverse effects; D055815:Young Adult
chemical_list: C496124:FCGR3A protein, human; D017452:Receptors, IgG; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone