This study mainly aimed to illuminate the impact of matched and mismatched MDR1 G2677TA, C1236T, C3435T donor-recipient on prognosis of patients after allo-HSCT. As results of our analysis, we concluded that matched MDR1 G2677TA donor-recipient was associated with an increased risk of NRM, and poor OS and DFS. However, we failed to observe differences in survival between MDR1 C1236T, C3435T matched and mismatched donor-recipient group.
Especially, in matched MDR1 G2677TA donor-recipient group, male patients had worse OS and PFS than female, which was not found in the whole cohort. And the OS and PFS of MDR1 G2677TA matched patients with PT, HCT-CI ≥ 1, and serum creatinine > 137.2umol/L was also significantly shorter than patients with PT, HCT-CI ≥ 1, and serum creatinine > 137.2umol/L in the whole group. For example, the OS and DFS of patients with PT was 52.1% and 40%, while patients in matched MDR1 G2677TA group developed PT, the OS and DFS was 33.3% and 21.4%. What’s more, the OS and PFS of patients with serum creatinine > 137.2umol/L was 33.3% and 27.8%, respectively while those patients in matched MDR1 G2677TA group developed AKI and serum creatinine > 137.2umol/L, the OS and PFS was 12.5% and 0. It seemed that matched MDR1 G2677TA donor-recipient was really an important risk factor for the prognosis of patients after allo-HSCT.
At present, research about the impact of donor and recipient MDR1 G2677TA match on the outcomes of patients after allo-HSCT was limited. Previous studies have shown that MDR1 SNPs have the ability to alter the function of P-glycoprotein which is encoded by MDR1 gene, and influence the efficiency of drugs absorption or elimination[11]. Published reports have demonstrated that cyclosporin, tacrolimus, imatinib et al are substrates of P-glycoprotein–mediated efflux[12–13]. Cyclosporine and tacrolimus are widely used in immunosuppressive regimens to prevent and treat GVHD in allo-HSCT. Many studies have reported the correlations between MDR1 gene polymorphisms and cyclosporin and tacrolimus concentration, which may explain the reason of the poor prognosis of patients with matched MDR1 G2677TA[14–17]. Casto AM et al[18] have also reported that only the donor MDR1 C3435T genotype was a risk factor for CMV reactivation by altering the efflux of cyclosporine and tacrolimus from donor lymphocytes. We cannot perfectly explain this relationship, and more clinical and basic researches are needed to clarify.
In our whole cohort, we tried to discovery associations between complications after allo-HSCT and survival. The timeline of complications from transplant permission through duration of follow up was shown in Fig. 6. We collected common complications of patients after allo-HSCT, such as myeloid and platelet engraftment failure, acute and chronic GVHD, EBV and CMV reactivation, PT, HC and AKI et al. And the discoveries demonstrated that the survival of patients after allo-HSCT accompanied with HC, CMV, and EBV were similar with patients without these complications, which were similar with previous studies[19–21]. But when the virus load > 4080copies/ml in CMV reactivation patients, their prognosis would get worse results[20]. More importantly, just like other published reports[22–24], patient with HCT ≥ 1, AKI and PT had bad prognosis. Further analysis was performed to clarify the relationship between serum creatinine and prognosis. Unfortunately, the serum creatinine of AKI patients after allo-HSCT higher than 137.2umol/L had significantly shorter OS and DFS. Several retrospective studies have revealed that stage 3 AKI has been associated with increased NRM in patient[25], which were similar with our results.
Although there are foundings revealed by our study, some limitations of its are evident. First, the cohort of our donors and recipients examined are small and it would be better to be confirmed by a much larger number of donors and recipients. Furthermore, our study should collect data about the cyclosporine concentration of patients in order to explain perfectly the relationship between donor-recipient MDR1 matched and the survival. Because of too many confounding factors affecting the concentration of cyclosporine, we finally quitted.