3.4 Association of donor CSF3R SNPs with relapse and TRM
Relapse occurred in 50 patients, including 38 patients who died of relapse and 12 patients who remained alive after treatment. None of the rs2275471, rs78861150, rs3917981, rs150501885, or rs2275472 polymorphisms were associated with the rate of relapse except for the rs3917980G/G or A/G genotype (p=.082) (Fig 2A). However, multivariate analysis including rs3917980 and disease risk showed no significant association (HR=1.6; 95% CI: 0.57-4.7, p=.366) (Table 3 and Fig 5). Further subgroup analyses based on HLA loci showed that relapse had no association with rs3917980 in recipients receiving haplo-HSCT (p=.27), and none of those six SNPs were associated with relapse in the HLA-matched all-HSCT group (data not shown). Moreover, in this study, AML, MDS and CML were classified as myeloid leukemia, and ALL was classified as lymphocytic leukemia to elucidate whether there is a correlation between CSF3R SNPs and relapse in the above subgroup. The results showed that the rs3917980G/G or A/G genotype correlated with a lower incidence of relapse in the myeloid leukemia subgroup (p=.047) (Fig 2B).
Regarding the association between CSF3R SNPs and TRM, only the rs2275472T/C genotype was associated with a lower incidence of TRM (Fig 2C, p=.0031); however, further multivariate analysis showed no statistically significant association (Table 3). In subgroup analyses, this effect was confirmed in HLA-mismatched and HLA-matched recipients, as cumulative analysis showed that there was a significant association between the rs2275472T/C genotype and TRM (p=.043 and p=.032) (Fig 2D and 2E), while no associations were found in any of the rs2275471, rs78861150, rs3917981, rs3917980, and rs150501885 CSF3R SNPs (p>.05).
In view of the close correlation between TRM and SNPs, we aimed to understand the reasons for the increasing incidence of TRM caused by the rs2275472T/C genotype. By analyzing correlations among post-transplantation infection, GVHD, platelet implantation, neutrophil implantation and SNPs, we found no evidence of an effect of the CSF3R SNP genotype on the incidence of aGVHD, and this result was further proven in all HLA-unmatched and HLA-matched patients. The genotypes of these six CSF3R SNPs did not influence the incidence of cGVHD and CMV (data not shown). However, the engraftment of PLTs was an independent protective factor against TRM (HR=0.048, 95% CI: 0.024-0.098, p<.001) (Table 3). Cumulative analysis showed that good platelet implantation was associated with lower transplantation-related mortality (p<.000) (Fig 2F).