Abstract

The FcγRllla (FCGR3A) 158V/V allotype displays a higher antibody-dependent cellular cytotoxicity compared to the FCGR3A-158V/F or 158F/F allotype, leading to susceptibility to rheumatoid arthritis, better clinical response to rituximab in NHL, and lower risk of periodontitis. We tested the hypothesis that FCGR3A polymorphism influences the development of GVHD and GVL, and TRM. The FCGR3A-158V/F genotype was determined in 49 recipient and donor pairs who underwent HLA-matched SCT in our institute. Subjects with the recipient FCGR3A-158V/V allotype and the donor FCGRA-158V/V allotype were almost one-third and twice as likely to develop chronic GVHD respectively (Table 1). The recipients with the FCGR3A-158V/V allotype had a 60% increase in probability of 3-year TRM. Multivariate analysis showed that the recipient FCGR3A-158V/V allotype and the donor FCGRA-158V/V allotype were independent risk factors for chronic GVHD (HR = 0.8 and 1.2, respectively), as well as the unrelated donor BMT (HR = 1.6) and the related donor PBSCT (HR = 2.4). The recipient FCGR3A-158V/V was an independent predictor for 3-year TRM (HR = 4.0) with the high risk disease (HR = 3.0) and the cord blood transplantation (HR = 5.0). We conclude that the recipient and donor FCGR3A polymorphism is associated with the development of chronic GVHD and TRM after HLA-matched SCT. These findings could therefore be useful in selecting the donor and creating therapeutic strategies for improving the final outcome of allogeneic SCT. Besides, these raise the question of whether the genetic risk factor in a recipient might also be involved in the mechanisms of chronic GVHD.

Table 1

FCGR3A allotype 2–4 acute GVHD(HR) Chronic GVHD (HR) 3 YR TRM (HR) 
*P<0.05 
Recipient FCGR3A-158V/V 46% (1.2) 17%* (0.8*) 72%* (4.0*) 
Recipient FCGR3A-158V/F or 158F/F 39% 57% 44% 
Donor FCGR3A-158V/V 46% (1.1) 67%* (1.2*) 43% (0.5) 
Donor FCGR3A-158V/F or 158F/F 38% 30% 50% 
FCGR3A allotype 2–4 acute GVHD(HR) Chronic GVHD (HR) 3 YR TRM (HR) 
*P<0.05 
Recipient FCGR3A-158V/V 46% (1.2) 17%* (0.8*) 72%* (4.0*) 
Recipient FCGR3A-158V/F or 158F/F 39% 57% 44% 
Donor FCGR3A-158V/V 46% (1.1) 67%* (1.2*) 43% (0.5) 
Donor FCGR3A-158V/F or 158F/F 38% 30% 50% 

Disclosures: No relevant conflicts of interest to declare.

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