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).