Hu S S, Wu Y B, Zhu P P, Shi J M, Yu J, Zhao Y M, Lai X Y, Liu L Z, Fu H R, Huang H, Luo Y
Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China Institute of Hematology, Zhejiang University, Hangzhou 310000, China Department of Hematology, Jinhua People's Hospital, Jinhua 321000, China.
Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China Institute of Hematology, Zhejiang University, Hangzhou 310000, China.
Zhonghua Xue Ye Xue Za Zhi. 2022 Dec 14;43(12):992-1002. doi: 10.3760/cma.j.issn.0253-2727.2022.12.004.
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. 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% ) . 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 (=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 (>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) % . (94.77±1.75) % , =0.004; (91.45±2.63) % . (95.54±2.05) % , =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) % . (95.08±1.41) % , =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 (=0.054) . Patients accepting daughter donors and son donors had a 3-year incidence of moderate and severe cGVHD that was 40.07% . 27.41% , respectively, among those over 35 (40.07±6.65) % . (27.41±4.54) % (=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) % . (95.08±0.95) % , =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) % . (94.49±1.45) % , =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) % . (95.62±1.26) % , =0.404]. 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.
探讨供受者性别差异对兔抗人胸腺细胞球蛋白（ATG）联合单纯外周血干细胞（PBSC）造血干细胞移植（haplo-HSCT）治疗恶性血液病疗效的影响。2015年2月至2020年9月，648例血液系统恶性肿瘤患者在浙江大学第一附属医院骨髓移植中心接受清髓性预处理方案的haplo-HSCT治疗。中位年龄为32（14 - 62）岁，其中男性363例（56.0%），女性285例（44.0%）。急性淋巴细胞白血病（ALL）242例（37.3%），急性髓系白血病（AML）293例（45.2%），骨髓增生异常综合征（MDS）56例（8.7%），非霍奇金淋巴瘤（NHL）27例（4.2%），其他血液系统恶性肿瘤30例（4.6%）。①全组3年总生存（OS）率、无病生存（DFS）率、Ⅱ - Ⅳ级急性移植物抗宿主病（aGVHD）发生率、Ⅲ - Ⅳ级aGVHD发生率、3年中重度慢性移植物抗宿主病（cGVHD）发生率、重度cGVHD发生率、3年复发率及非复发死亡率（NRM）分别为（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）%、（9.80±1.24）%。②供受者性别匹配组与供受者性别不匹配组在28天累积中性粒细胞植入率、28天累积血小板植入率、Ⅱ - Ⅳ级aGVHD发生率、Ⅲ - Ⅳ级aGVHD发生率、3年OS率、3年DFS率、复发累积发生率、NRM及中重度cGVHD发生率、重度cGVHD发生率方面差异均无统计学意义。③男女、女女、男男及女男组间28天累积中性粒细胞植入率差异无统计学意义（P = 0.148）。四组间Ⅱ - Ⅳ级aGVHD发生率、Ⅲ - Ⅳ级aGVHD发生率、3年OS率、3年DFS率、累积复发率及NRM以及cGVHD发生率差异均无统计学意义（P>0.05）。女男组28天累积血小板植入率显著低于男女组及女女组[（91.45±2.63）%、（94.77±1.75）%，P = 0.004；（91.45±2.63）%、（95.54±2.05）%，P = 0.005]。女男组与男男组28天累积血小板植入率差异无统计学意义[（91.45±2.63）%、（95.08±1.41）%，P = 0.284]。④年龄≤35岁患者中，接受姐妹供者和同胞供者的患者3年重度cGVHD发生率分别为（26.71±5.90）%和（10.33±4.43）%（P = 0.054）。接受女儿供者和儿子供者的35岁以上患者中，中重度cGVHD的3年发生率分别为40.07%、27.41%[（40.07±6.65）%、（27.41±4.54）%，P = 0.084]。⑤女性供者至男性受者的28天累积血小板植入率显著低于其他组[（91.45±2.63）%、（95.08±0.95）%，P = 0.037]。⑥在ATG - Fresenius（ATG - F）10 mg/kg组中，女性供者至男性受者的28天累积血小板植入率显著低于其他组[（89.29±4.29）%、（94.49±1.45）%，P = 0.037]。但在兔抗人胸腺细胞免疫球蛋白（rATG - T）6 mg/kg组中，女性供者与男性受者间28天累积血小板植入率差异无统计学意义[（93.44±3.38）%、（95.62±1.26）%，P = 0.404]。基于ATG和PBSC来源的haplo - HSCT模式下，供者与患者的性别组合对恶性血液病患者移植后的主要临床结局无影响。女性供者至男性受者的28天累积血小板植入率较低，血小板植入时间较长。
