化疗联合供者淋巴细胞输注对异基因造血干细胞移植后微小残留病阳性患者慢性移植物抗宿主病及预后的影响

OBJECTIVE: To explore clinical features and severity of chronic graft-versus-host disease (cGVHD) after chemotherapy plus donor lymphocyte infusion (Chemo-DLI) in a consecutive cohort of acute leukemia patients who were minimal residual disease (MRD) positive after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The global scoring system proposed by National Institutes of Health (NIH) Consensus Conference was used to identify the characteristics and severity of cGVHD in patients who MRD positive after Chemo-DLI. RESULTS: 54 (59.3%) patients were diagnosed with cGVHD after Chemo-DLI, with the median time of onset of 70 (13–504) days. There were 6 cases (6.6%) of mild cGVHD, 21 cases (23.1%) of moderate cGVHD and 27 cases (29.7%) of severe cGVHD.The 5-year cumulative incidence of relapse after Chemo-DLI was 61.9% (95%CI 45.3%–78.5%), 15.1% (95%CI 1.1%–29.1%), and 26.6% (95%CI 9.2%–44.0%) (χ(2)=18.901, P<0.001) in non-cGVHD, mild to moderate cGVHD, and severe cGVHD groups, respectively. The 5-year cumulative incidence of relapse after Chemo-DLI was 61.9% (95%CI 45.3%–78.5%), 19.9% (95%CI 8.1%–31.7%), and 28.6% (95%CI 0.0%–65.0%) (χ(2)=18.307, P<0.001) in non-cGVHD, classical cGVHD, and overlap syndrome groups, respectively. cGVHD was not associated with non-relapse morality after Chemo-DLI. Probabilities of 5-year leukemia-free survival (LFS) after Chemo-DLI were 24.0% (95%CI 9.1%–38.9%), 77.2% (95%CI 60.8%–93.6%), and 64.9% (95%CI 45.7%–84.1%) (χ(2)=24.447, P<0.001) in non-cGVHD, mild to moderate cGVHD, and severe cGVHD groups, respectively. Probabilities of 5-year LFS after Chemo-DLI were 24.0% (95%CI 9.1%–38.9%), 75.5% (95%CI 62.7%–88.3%), and 42.9% (95%CI 1.8%–84.0%) (χ(2)=25.665, P<0.001) in non-cGVHD, classical cGVHD, and overlap syndrome groups, respectively. Probabilities of 5-year overall survival (OS) after Chemo-DLI were 50.0% (95%CI 31.1%–68.9%), 87.9% (95%CI 74.7%–100.0%), and 71.0% (95%CI 52.0%–90.0%) (χ(2)=9.517,P=0.009) in non-cGVHD, mild to moderate cGVHD, and severe cGVHD groups, respectively. Probabilities of 5-year OS after Chemo-DLI were 50.0% (95%CI 31.1%–68.9%), 83.9% (95%CI 72.8%–95.0%), and 51.4% (95%CI 6.2%–96.6%) (χ(2)=10.673, P=0.005) in non-cGVHD, classical cGVHD, and overlap syndrome groups, respectively. In multivariate analysis, patients receiving allo-HSCT in first complete remission stage and classical cGVHD after Chemo-DLI were associated with lower relapse risk and better survival. CONCLUSION: These findings highlight the close relation between cGVHD and the graft-versus-leukemia effect in patients who were MRD positive and received Chemo-DLI after allo-HSCT. However, overlap syndrome could not improve the clinical outcomes of these patients.