Jiang Jieling, Li Xiaofan, Wu Dong, Lu Quanyi, Miao Kourong, Wang Houcai, Li Xiaoping, Chen Yingnian, Zhou Shiyuan, Zhou Yali, Liao Guiping, Jiang Chuanhe, Yuan Xiaohong, Zhao Youshan, Chang Chunkang, Chen Jie, Zhu Han, Ma Ruye, Li Nainong, Yin Xiaolin, Wu Xiaojin, Wang Sanbin, Wang Chun, Hu Jiong
Department of Hematology. Shanghai Institute of Hematology Blood & Marrow Transplantation Center Collaborative Innovation Center of Hematology Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital Shanghai China.
Department of Hematology Fujian Medical University Union Hospital Fuzhou China.
EJHaem. 2024 Jul 8;5(4):757-767. doi: 10.1002/jha2.947. eCollection 2024 Aug.
Relapse remains the main cause of treatment failure in patients with myeloid malignancies even after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We observed a particularly low incidence of relapse in patients prepared with fludarabine, busulfan and melphalan in our previous study and this multicenter retrospective analysis aimed to confirm the feasibility of the regimen and to identify the potential prognostic factors. This study was performed using registry data from adults patients with myeloid malignancies who underwent their first allo-HSCT following fludarabine(≥100 mg/m), busulfan (≥3.2 mg/kg) and melphalan (≥100 mg/m) based conditioning at nine transplantation centers in China between Jan. 2020 and Mar. 2022. A total of 221 consecutive patients (AML = 171, MDS-IB-1 or 2 = 44, CMML = 6) with median age of 46 were enrolled in this study. The median follow-up was 507 days for survivors. The 2-year NRM, CIR, OS and DFS were 10.6% ± 2.2%, 14.8% ± 3.3%, 79.4% ± 3.7% and 74.6% ± 3.7%, respectively. In multivariate analyses, high HCT-CI (≥3) was the only independent factor for higher NRM [hazard ratio (HR), 2.96; 95% confidence interval (CI), 1.11 to 7.90; = 0.030] and ECOG score ≥2 was the only independent factor for inferior OS (HR, 2.43; 95%CI, 1.15 to 5.16; = 0.020) and DFS (HR, 2.12; 95%CI, 1.13 to 4.02; = 0.020). AML diagnosis and positive measurable residual disease (MRD) at transplantation were predictors for higher CIR (HR = 7.92, 95%CI 1.05-60.03, = 0.045; HR = 3.64, 95%CI 1.40-9.44, = 0.008; respectively), while post-transplantation cyclophosphamide based graft-versus-host disease prophylaxis was associated with lower CIR (HR = 0.24 95%CI 0.11-0.54, = 0.001). The intensity of conditioning regimen did not impact CIR, NRM, DFS and OS. These results supported that double alkylating agents of busulfan and melphalan based conditioning regimens were associated with low relapse rate and acceptable NRM in adult patients with myeloid malignancies. The optimal dose remained to be confirmed by further prospective studies.
即使在异基因造血干细胞移植（allo-HSCT）后，复发仍然是髓系恶性肿瘤患者治疗失败的主要原因。在我们之前的研究中，我们观察到接受氟达拉滨、白消安和马法兰预处理的患者复发率特别低，这项多中心回顾性分析旨在确认该方案的可行性，并确定潜在的预后因素。本研究使用了2020年1月至2022年3月期间在中国9个移植中心接受首次allo-HSCT的成年髓系恶性肿瘤患者的登记数据。共有221例连续患者（急性髓系白血病[AML]=171例，骨髓增生异常综合征-国际预后积分系统[MDS-IPSS]-1或2级=44例，慢性粒-单核细胞白血病[CMML]=6例）入组本研究，中位年龄为46岁。幸存者的中位随访时间为507天。2年的非复发死亡率（NRM）、复发率（CIR）及总生存率（OS）和无病生存率（DFS）分别为10.6%±2.2%、14.8%±3.3%、79.4%±3.7%和74.6%±3.7%。在多变量分析中，高造血细胞移植合并症指数（HCT-CI）（≥3）是NRM升高的唯一独立因素[风险比（HR），2.96；95%置信区间（CI），1.11至7.90；P=0.030]，东部肿瘤协作组（ECOG）评分≥2是OS（HR，2.43；95%CI，1.15至5.16；P=0.020）和DFS（HR，2.12；95%CI，1.13至4.02；P=0.020）较差的唯一独立因素。AML诊断和移植时可测量残留病（MRD）阳性是CIR升高的预测因素（HR=7.92，95%CI 1.05-60.03，P=0.045；HR=3.64，95%CI 1.40-9.44，P=0.008；分别），而移植后基于环磷酰胺预防移植物抗宿主病与较低的CIR相关（HR=0.24，95%CI 0.11-0.54，P=0.001）。预处理方案的强度不影响CIR、NRM、DFS和OS。这些结果支持，基于白消安和马法兰的双烷化剂预处理方案与成年髓系恶性肿瘤患者的低复发率和可接受的NRM相关。最佳剂量仍有待进一步的前瞻性研究来证实。
