减低强度预处理并更换供者二次异基因造血干细胞移植治疗移植后复发恶性血液病44例临床研究

OBJECTIVE: The purpose of this study was to assess the safety and efficacy of a second allogeneic hematopoietic stem cell transplantation（allo-HSCT）with reduced-intensity conditioning（RIC）in patients with hematological malignancies who had relapsed after the first allo-HSCT. METHODS: Between April 2018 and June 2021, 44 patients with hematological malignancies（B-ALL 23, T-ALL/T-LBL 4, AML15, and MDS 2）were enrolled and retrospectively examined. Unrelated donors（n＝12）or haploidentical donors（n＝32）were used. Donors were replaced in all patients for the second allo-HSCT. Hematological and immunological germline predisposition genes and hematopoietic and immune function tests were used to select the best-related donor. Total body irradiation（TBI）/fludarabine（FLU）-based（n＝38）, busulfan（BU）/FLU-based（n＝4）, total marrow irradiation（TMI）/FLU-based（n＝1）, and BU/cladribine-based（n＝1）were the RIC regimens used. For graft versus host disease（GVHD）prevention, cyclosporine, mycophenolate mofetil, short-term methotrexate, and ATG were used. Eighteen（40.9％）of 44 patients with gene variations for which targeted medications are available underwent post-transplant maintenance therapy. RESULTS: The median age was 25 years old (range: 7–55). The median interval between the first and second HSCT was 19.5 months (range: 6–77). Before the second allo-HSCT, 33 (75％) of the patients were in complete remission (CR), whereas 11 (25％) were not. All patients had long-term engraftment. The grade Ⅱ–Ⅳ GVHD and severe acute GVHD rates were 20.5％ and 9.1％, respectively. Chronic GVHD was found in 20.5％ of limited patterns and 22.7％ of severe patterns. CMV and EBV reactivation rates were 29.5％ and 6.8％, respectively. Hemorrhage cystitis occurred in 15.9％ of cases, grade Ⅰ or Ⅱ. The 1-yr disease-free survival (DFS), overall survival (OS), and cumulative recurrence incidence (RI) rates of all patients were 72.5％ (95％ CI, 54.5％–84.3％), 80.6％ (95％ CI, 63.4％–90.3％), and 25.1％ (95％ CI, 13.7％–43.2％), respectively, with a median follow-up of 14 (2–39) months. There were eight deaths (seven relapses and one infection). The rate of non-relapse mortality (NRM) was only 2.3％. The CR patients' 1-yr RI rate was significantly lower than the NR patients (16.8％ vs 48.1％, P＝0.026). The DFS rate in CR patients was greater than in NR patients, although there was no statistical difference (79.9％ vs 51.9％, P＝0.072). Univariate analysis revealed that CR before the second allo-HSCT was an important prognostic factor. CONCLUSION: With our RIC regimens, donor change, and post-transplant maintenance therapy, the second allo-HSCT in relapsed hematological malignancies after the first allo-HSCT is a safe and effective treatment with high OS and DFS and low NRM and relapse rate. The most important factor influencing the prognosis of the second allo-HSCT is the patient's illness condition before the transplant.