供患者性别组合对恶性血液病患者单倍体造血干细胞移植结局的影响

OBJECTIVE: To investigate how gender differences between the donor and the recipient affect the effectiveness of antithymocyte globulin (ATG) and pure peripheral blood stem cell (PBSC) hematopoietic stem cell transplantation (haplo-HSCT) in the treatment of malignant hematological diseases. METHODS: From February 2015 to September 2020, 648 hematological malignancies patients underwent myeloablative condition regimen haplo-HSCT treatment at the Bone Marrow Transplant Center of the First Affiliated Hospital of Zhejiang University. The median age was 32 (14–62) years, with 363 males (56.0％) and 285 females (44.0％) present. 242 cases of acute lymphoblastic leukemia（ALL）（37.3％）, 293 cases of acute myeloid leukemia（AML）（45.2％）, 56 cases of myelodysplastic syndrome（MDS）（8.7％）, 27 cases of non-Hodgkin's lymphoma（NHL）（4.2％）, and 30 cases of other hematological malignancies（4.6％）. RESULTS: ① The 3-year overall survival（OS）, DFS, the incidence of Ⅱ–Ⅳ grade acute graft-versus-host disease（aGVHD）, the incidence of Ⅲ–Ⅳ grade aGVHD, the 3-year incidence of moderate & severe chronic GVHD（cGVHD）, severe cGVHD, the 3-year incidence of relapse, and NRM of the whole group were（73.10±1.90）％,（70.80±1.90）％,（33.96±1.87）％,（13.08±1.33）％,（35.10±2.14）％,（10.66±1.38）％,（19.43±1.67）％, and（9.80±1.24）％, respectively. ②There was no statistically significant difference between the donor-recipient gender match and donor-recipient gender mismatch groups in the 28-day cumulative neutrophil engraftment rate, 28-day cumulative platelet engraftment rate, the incidence of Ⅱ–Ⅳ grade aGVHD, the incidence of Ⅲ–Ⅳ grade aGVHD, 3-year OS, 3-year DFS, the cumulative incidence of relapse, NRM, and incidence of moderate & severe cGVHD, severe cGVHD. ③The 28-day cumulative neutrophil engraftment rate did not differ statistically between the male-female, female-female, male-male, and female-male groups（P＝0.148）. The incidence of Ⅱ–Ⅳ grade aGVHD, the incidence of Ⅲ–Ⅳ grade aGVHD, 3-year OS, 3-year DFS, cumulative relapse rate, and NRM, and the incidence of cGVHD were not statistically different among the four groups（P>0.05）. The 28-day cumulative platelet engraftment rate of the female-male group was significantly lower than male-female group, and the female-female group［（91.45±2.63）％ vs.（94.77±1.75）％, P＝0.004;（91.45±2.63）％ vs.（95.54±2.05）％, P＝0.005］. No significant difference existed in the 28-day cumulative platelet engraftment rate between the female-male group and the male-male group［（91.45±2.63）％ vs.（95.08±1.41）％, P＝0.284］. ④Among patients ≤35 years old, the 3-year incidence of severe cGVHD patients receiving sister donors and sibling donors were（26.71±5.90）％ and（10.33±4.43）％, respectively（P＝0.054）. Patients accepting daughter donors and son donors had a 3-year incidence of moderate and severe cGVHD that was 40.07％ vs. 27.41％, respectively, among those over 35（40.07±6.65）％ vs.（27.41±4.54）％（P＝0.084）. ⑤Female donors to male recipients had a significantly lower 28-day cumulative platelet engraftment rate compared to the other groups［（91.45±2.63）％ vs.（95.08±0.95）％, P＝0.037］. ⑥ Female donors to male recipients had a significantly lower 28-day cumulative platelet engraftment rate than the other groups in the ATG-Fresenius（ATG-F）10 mg/kg group［（89.29±4.29）％ vs.（94.49±1.45）％, P＝0.037］. But when compared to the other groups in the Rabbit Antihuman Thymocyte Immunoglobulin（rATG-T）6 mg/kg group, the 28-day cumulative platelet implantation rate between female donors and male recipients was not significantly different［（93.44±3.38）％ vs.（95.62±1.26）％, P＝0.404］. CONCLUSION: The main clinical outcomes of patients with malignant blood diseases following transplantation are unaffected by the gender combination of the donor and patient in the haplo-HSCT mode based on ATG and PBSC sources. Female donors to male recipients have a lower 28-day cumulative platelet engraftment rate and longer platelet engraftment times.