恶性血液病单倍型造血干细胞移植预处理中兔抗人胸腺细胞球蛋白剂量优化探讨

OBJECTIVE: To compare the clinical efficacy of different doses of rabbit antithymocyte globulin (rATG) in haplo-HSCT in the treatment of hematologic malignancies. METHODS: Malignant hematological patients treated at our hospital from March 2013 to December 2018 were retrospectively analyzed. These patients were divided into three groups as per three doses of ATG (6 mg/kg, 7.5 mg/kg, and 9 mg/kg) in the conditioning regimens. The transplant outcomes were compared in terms of the occurrence of acute graft versus host disease (GVHD), infection, and survival. RESULTS: ①Total 288 patients were enrolled in the study, including 182 men and 106 women, with a median age of 18 (6–62) years. Total 110 patients were diagnosed with acute lymphoblastic leukemia (ALL), 128 with acute myelogenous leukemia (AML), 8 with chronic myeloid leukemia (CML), 28 with myelodysplastic syndrome (MDS), and 14 with mixed cell leukemia (MAL). There were 159 patients in the ATG-6 group, 72 in the ATG-7.5 group, and 57 in the ATG-9 group. The median follow-up time of post transplantation was 14 (0.2–74) months. ②The incidence of neutrophil engraftment (96.9%, 97.2%, and 96.5%, respectively) and platelet engraftment (92.5%, 87.5%, and 86%, respectively) did not significantly differ among the ATG-6, ATG-7.5, and ATG-9 groups (P=0.972, P=0.276). The incidence of grades 2–4 acute GVHD was 14.5%, 11.1%, and 8.8% in the three groups, respectively (P=0.493), chronic GVHD incidence in the three group was 8.8%, 14.3% and 12.0%, respectively (P=0.493). The infection rates of CMV and EBV in the ATG-9 group (77.2% and 12.5%) were significantly higher than those in the ATG-6 (43.3% and 3.5%), and ATG-7.5 group (44.4% and 1.5%) (P<0.001 and P=0.033, respectively). ③Among the three groups, there were no significant difference in the 3-year overall survival [68.5% (95% CI 60.3%–77.9%), 60.1% (95% CI 48.3%–74.8%), 64.7% (95% CI 51.9%–80.7%)], cumulative incidences of relapse [34.6% (95% CI 34.3%–35.1%), 38.0% (95% CI 37.3%–38.7%), 20.6% (95% CI 20.0%–21.3%)], disease-free survival [53.3% (95% CI 44.9%–63.4%), 51.9% (95% CI 41%–65.8%), 63.9% (95% CI 51.9%–78.7%)] and non-relapse mortality [24.2% (95% CI 23.8%–24.5%), 26.0% (95% CI 25.4%–26.6%), 23.6% (95% CI 26.3%–28.2%)] (P=0.648, P=0.165, and P=0.486 and P=0.955). CONCLUSION: Low dose (6 mg/kg) of rATG may increase the risk of grade Ⅱ–Ⅳ aGVHD, and a high dose (9 mg/kg) of ATG could significantly increase the risk of CMV and EBV infection. Median dose (7.5 mg/kg) of ATG is expected to reduce the incidence of moderate to severe aGVHD and viral infections without increasing the mortality.