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.
目的： 评估减低强度预处理（RIC）、更换供者二次异基因造血干细胞移植（二次移植）治疗移植后复发恶性血液病的疗效及安全性。 方法： 纳入2018年4月至2021年6月于北京高博博仁医院造血干细胞移植科接受RIC、更换供者二次移植的44例移植后复发恶性血液病患者，回顾性分析其临床资料。 结果： ①全部44例患者中男21例，女23例，中位年龄25（7~55）岁；急性B淋巴细胞白血病23例，急性T淋巴细胞白血病/T淋巴母细胞性淋巴瘤4例，急性髓系白血病15例，骨髓增生异常综合征2例；首次allo-HSCT供者类型包括无关供者12例、单倍体供者32例，所有患者在二次移植时均更换了供者；两次allo-HSCT间隔的中位时间为19.5（6~77）个月；二次移植前33例（75.0%）患者原发病为完全缓解，11例（25.0%）为未缓解；预处理方案包括全身放射治疗/氟达拉滨（38例）、白消安/氟达拉滨（4例）、全骨髓照射/氟达拉滨（1例）、白消安/克拉屈滨（1例）；采用环孢素A、霉酚酸酯、短程甲氨蝶呤及抗胸腺细胞球蛋白预防移植物抗宿主病（GVHD）。②所有患者均获得造血重建，Ⅱ~Ⅳ度、Ⅲ~Ⅳ度急性GVHD发生率分别为20.5%、9.1%，局限型、广泛型慢性GVHD发生率分别为20.5%、22.7%，巨细胞病毒、EB病毒感染发生率分别为29.5%、6.8%，出血性膀胱炎发生率为15.9%（均为Ⅰ~Ⅱ度）。③中位随访14（2~39）个月，移植后1年无病生存率、总生存率分别为72.5%（95% CI 54.5%~84.3%）、80.6%（95% CI 63.4%~90.3%），累积复发率为25.1%（95% CI 13.7%~43.2%）。8例患者死亡，7例死于复发，1例死于感染，非复发死亡率为2.3%。④二次移植前完全缓解组、未缓解组移植后1年累积复发率分别为16.8%、48.1%（P=0.026），无病生存率分别为79.9%、51.9%（P=0.072）。⑤单因素分析显示二次移植前原发病是否完全缓解是预后的影响因素。 结论： 采用RIC方案、更换供者及移植后维持治疗等策略的二次移植治疗allo-HSCT后复发的恶性血液病具有较好的安全性及疗效。影响二次移植预后的最重要因素是二次移植前的疾病状态。.
Keywords: Donor; Hematological malignancy; Reduced-intensity conditioning; Second allogeneic hematopoietic stem cell transplantation.