Low-dose decitabine-intensified modified conditioning regimen alleviates aGVHD in AML/MDS patients treated with allogeneic hematopoietic stem cell transplantation

低剂量地西他滨强化改良预处理方案可减轻接受异基因造血干细胞移植的AML/MDS患者的急性移植物抗宿主病(aGVHD)。

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Abstract

BACKGROUND: The widespread adoption of Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT) has significantly improved the survival rates of patients with hematological malignancies. However, Graft-Versus-Host Disease (GVHD) remains a formidable complication, threatening patient prognosis. Recent research has indicated that decitabine (DAC), known for its hypomethylating properties may also exhibit immune-regulatory capabilities and a potential for reducing GVHD incidence and enhancing survival. METHODS: We retrospectively reviewed data from AML/MDS patients who underwent Allo-HSCT at our center from January 2010 to January 2023. From a total of 251 patients with complete data, we employed propensity score matching (PSM) to create 100 matched pairs (200 patients) for comprehensive trial analysis. Patients receiving low-dose DAC-containing regimen were matched with those who did not receive DAC. RESULTS: Patients in the DAC group exhibited a significantly lower incidence of grade II-IV acute GVHD (aGVHD) compared to non-DAC group (21% vs. 38%, P=0.013). Univariable and multivariable logistic regression analysis demonstrated DAC intervention as a protective factor against grade II-IV aGVHD (P=0.017, OR=0.47, 95% CI 0.23-0.81; P=0.018, OR=0.46, 95% CI 0.24-0.87). Multivariate competing risk regression further supported administration of decitabine as a protective factor against grade II-IV aGVHD (P=0.038, SHR=0.53, 95%CI 0.29-0.97). There was no significant difference between both groups concerning chronic GVHD, infection, disease relapse, overall survival, disease-free survival and GVHD free, relapse free survival. In MRD negative or intermediate risk subgroup, the grade II-IV aGVHD ameliorating effect of DAC was confirmed as well. CONCLUSION: Low-dose DAC-intensified modified conditioning regimen could improve prognosis in AML/MDS Patients treated with allogeneic hematopoietic stem cell transplantation.

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