单倍体造血干细胞移植治疗重型再生障碍性贫血76例疗效分析

OBJECTIVE: The purpose of this study is to determine the efficacy of haploidentical donor hematopoietic stem cell transplantation in the treatment of severe aplastic anemia. METHODS: The clinical data of 76 patients with severe aplastic anemia（SAA）patients who underwent haplo-HSCT from December 2014 to October 2020 were selectively analyzed. There were 50 males and 26 females with a median age of 16（3–52）years old. There were 49 SAA-Ⅰ patients, 18 SAA-Ⅱ patients, and 9 patients with hepatitis-associated aplastic anemia. There were 15 cases of bone marrow put together with peripheral blood stem cell transplantation and 61 cases of peripheral blood stem-cell transplantation. Conditioning regimens were Cyclophosphamide（CY）+ Fludarabine（Flu）+ATG for 46 patients and Busulfan（Bu）+ CY+Flu+ATG for 30 patients. RESULTS: Three patients died during the myelosuppressive phase following transplantation, and 73 patients had a median time of neutrophil engraftment of 12（9–21）days; in addition to 3 patients who died early, 8 patients did not obtain platelet reconstruction after transplantation, and 65 patients had platelet engraftment with a medium time of 14（9–90）d. The incidence of primary graft failure was 10.9％ and the incidence of secondary graft failure was 5.5％. The incidence of Ⅱ–Ⅳ acute graft-versus-host disease（aGVHD）was 38.4％, the incidence of Ⅲ–Ⅳ aGVHD was 16.4％, the incidence of chronic graft anti-host disease（cGVHD）was 35.8％, and the incidence of extensive cGVHD was 22.4％. The medium follow-up time was 19.5（1–75）months, the prospective overall survival（OS）for 2 years was（78.6±5.0）％, the failure-free survival（FFS）was（75.9±5.1）％, and the transplant-related mortality was（20.2±4.9）％. Multi-factor analysis revealed that the patient older than 35 years old, Ⅲ/Ⅳ aGVHD, HCT-CI≥3, the pre-transplant ferritin ≥1 500 µg/L, the number of neutrophils >1×10(9)/L at the time of onset were risk factors affecting OS（P＝0.008, 0.008, 0.014, 0.004, 0.027）. Patients with graft failure had lower OS and FFS than other patients（P<0.001）. CONCLUSION: Haplo-HSCT is an effective method for treating SAA in children, adolescents, and young patients, and the occurrence of severe aGVHD and severe infection, as well as graft failure, are the main causes of survival rate. The prevention and treatment of severe aGVHD and infection are essential to improve efficacy.