The impact of matched and mismatched donor–recipient genotypes for MDR1 polymorphisms (G2677TA, C1236T and C3435T) on the outcomes of patients after allogeneic haematopoietic stem cell transplantation

Author:

Duan Ziwen1,Zhang Xiao2,Liu Yanping1,Wang Jiawen1,Zhu Han1,Chen Ruize1,Xu Wei1ORCID,Miao Kourong1ORCID

Affiliation:

1. Department of Hematology The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital Nanjing China

2. Department of Hematology The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology Suzhou China

Abstract

SummaryIn this study, we investigated whether matched and mismatched multidrug resistance gene (MDR1) genotypes (G2677TA, C1236T and C3435T) were associated with prognosis in patients after allogeneic haematopoietic stem cell transplantation (allo‐HSCT). One hundred patients after transplantation and their donors were enrolled. Matched MDR1 G2677TA donor–recipient was associated with an increased risk of non‐relapse mortality (NRM) (29.5% vs. 6.2%, p = 0.002), poor overall survival (OS) (51.7% vs. 63.8%, p = 0.024) and disease‐free survival (DFS) (38.6% vs. 67%, p = 0.005). There were no differences in OS, DFS or NRM between MDR1 C1236T‐ and C3435T‐matched and ‐mismatched groups. Subgroup analysis suggested that within the matched MDR1 G2677TA group, male gender, haematopoietic cell transplantation‐specific comorbidity index ≥1, serum creatinine >137.2 μmol/L and post‐transplantation thrombocytopenia were associated with poor survival. Our results demonstrated that patients receiving matched MDR1 G2677TA allo‐HSCT experienced a poorer prognosis compared with the mismatched group. The potential mechanism may involve increased expression of P‐glycoprotein, leading to decreased accumulation of antimicrobial agents and ultimately contributing to the progression of inflammation. This identification of MDR1 G2677TA genotype compatibility holds promise as a valuable molecular tool for selecting donors for allo‐HSCT.

Publisher

Wiley

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