Objective: To investigate the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS) and secondary acute myelogenous leukemia (MDS-AML) using conditioning regimen with busulfan (Bu) and increased-dose of fludarabine (ID-Flu).
Methods: A total of 49 patients with MDS or MDS-AML were treated by allo-HSCT, the clinical data was analyzed retrospectively.
Results: All patients achieved hematopoietic reconstitution. Neutrophil engraftment was at 10 - 22 days (median 13 days), and platelet engraftment was at 8 - 66 days (median 16 days). The cumulative incidences of Ⅱ-Ⅳ degree acute graft-versus-host disease (GVHD), hemorrhagic cystitis (HC), and hepatic venous occlusive disease (VOD) were 28.6%, 14.3% and 2.0%, respectively. The transplant-related mortality (TRM) was only 4.1% at 100d and 8.2% at 1-92 months of followed-up (median 14 months) period. Overall survival (OS) and disease free survival (DFS) was 75.5%, 73.5%, respectively. Kaplan-Meier curve showed that 3-year OS and 3-year DFS was (71.1 ± 7.8)%, (66.7 ± 8.3)%, respectively, with a relapse incidence (RI) 16.3%. OS for MDS and MDS-AML was 81.5% and 68.2%, and RI in two settings was 3.7%, 31.8%, respectively. OS for MDS-AML at complete remission (CR) and non-CR subgroup was 83.3% and 50.0%, respectively, while cumulative RR was 16.7% and 50.0%, respectively. OS and RI except for non-CR subgroup were 82.1% and 7.7%. Univariate analysis showed that pre-HSCT disease status had correlation with OS (P=0.031), but age, decitabine in conditioning regimen, stem cell source, HLA matching, patient-donor gender, dose of mononuclear cells and GVHD had no correlation with OS.
Conclusion: Bu/ID-Flu conditioning regimen for MDS and MDS-AML has high efficiency, fewer complications, lower toxicity and TRM. The OS and DFS were higher and RI was lower except for refractory MDS-AML patients. The regimen is valuable for clinical application.
目的: 探讨白消安联合增加剂量氟达拉滨（Bu/ID-Flu）为主预处理方案进行异基因造血干细胞移植（allo-HSCT）治疗骨髓增生异常综合征（MDS）和MDS转化的急性髓系白血病（MDSAML）的疗效与安全性。
方法: 回顾性分析Bu/ID-Flu预处理方案进行allo-HSCT治疗27例MDS和22例MDS-AML患者的临床资料。
结果: 全部49例患者均达到造血重建。白细胞植活中位时间为13 (10~22) d，血小板植活中位时间为16 (8~66) d。Ⅱ~Ⅳ度急性移植物抗宿主病（GVHD）、出血性膀胱炎及肝静脉阻塞病的发生率分别为28.6%、14.3％和2.0%。移植后100 d和总体移植相关死亡率（TRM）分别为4.1 %（2/49）和8.2%（4/49）。中位随访14(1~92）个月，总生存（OS）率、无病生存（DFS）率分别为75.5%、73.5%。Kaplan-Meier分析示3年OS率、DFS率分别为（71.1±7.8）%、（66.7±8.3）%，复发率为16.3%。MDS、MDS-AML患者的OS率分别为81.5%（22/27）、68.2%（15/22），复发率分别为3.7%（1/27）、31.8%（7/22）。allo-HSCT前达完全缓解（CR）与未达CR的MDS-AML患者的OS率分别为83.3%（10/12）、50.0%（5/10），复发率分别为16.7%（2/12）、50.0%（5/10）。除化疗未达CR的MDS-AML患者（10例）外，其余39例患者的OS率及复发率分别为82.1 %（32/39）和7.7%（3/39）。单因素分析显示，移植前疾病状态是影响OS的高危因素（P=0.031），年龄、预处理中加入地西他滨、造血干细胞来源、HLA相合与否、供受者性别差异、输入CD34+细胞数和GVHD均不是影响OS的危险因素。
结论: 应用Bu/ID-Flu为主的预处理方案对MDS和MDS-AML患者进行allo-HSCT，造血功能恢复迅速、植入稳定，并发症发生率和TRM较低。除MDS-AML化疗未达CR患者外，OS率较高且复发率较低。