减低剂量Bu+Cy预处理方案进行异基因造血干细胞移植治疗白血病的效果观察

Therapeutic effect of allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning regimen of Bu+Cy for leukemia

目的观察采用减低剂量Bu+Cy预处理方案在白血病患者异基因造血干细胞移植中的应用价值。方法采用减低剂量Bu+Cy预处理方案:马利兰4 mg/(kg·d),3 d;环磷酰胺50 mg/(kg·d),2 d;兔抗胸腺细胞球蛋白(ATG)2.5 mg/(kg·d),2/4 d。行异基因造血干细胞移植治疗白血病共15例,其中急性淋巴细胞白血病2例,急性非淋巴细胞白血病3例,慢性粒细胞白血病9例,慢性粒细胞白血病急性粒细胞变1例。结果①造血重建:患者均顺利植入,中性粒细胞>0.5×109/L的中位时间为12(10～17)d,血小板>20×109/L的中位时间为15(12～27)d。30 d行短串联重复序列复合扩增(STR-PCR)检测均为完全嵌合型。②移植相关并发症:15例患者中6例(40.0%)发生急性移植物抗宿主病(aGVHD),其中Ⅰ度2例,Ⅱ度4例,无Ⅲ～Ⅳ度;8例(53.3%)发生慢性移植物抗宿主病(cGVHD),其中广泛型2例,局限型6例;3例(20.0%)出血性膀胱炎;4例(26.7%)血巨细胞病毒感染。③复发及生存情况:随访中位时间15.4(6～30)个月,1例(6.7%)移植相关死亡,2例(13.3%)血液学复发,余12例(80.0%)无病存活6～30个月。结论减低剂量Bu+Cy预处理方案行异基因造血干细胞移植,造血重建快,移植并发症少,术后复发率低,且预处理相关死亡率低,是治疗白血病安全有效的方法。

Objective To evaluate the clinical value of allogeneic hematopoietic stem cell transplantation （allo-HSCT） with reduced intensity Bu＋ Cy conditioning regimen in the treatment of patients with leukemia. Methods The reduced intensity Bu＋ Cy conditioning regimen including busulfan （Bu） 4 mg/（kg . d） , for 3 d; cyclophosphamide （Cy） 50 mg/（kg .d）, for 2 d, antithymocyte globulin （ATG） 2.5 mg/（kg .d）, for 2/4 d, were used in 15 leukemia patients who underwent allo-HSCT in our department from April 2010 to March 2012. There were 2 cases of acute lymphocytic leukemia, 3 cases of acute non-lymphoid leukemia, 9 cases of chronic myeloid leukemia, and 1 case of Crisis phase of CML. Results All patients achieved successful hemopoietic reconstruction. The median time of the neutrophil recovery 〉0.5 × 10^9/L was 12 （ ranging from 10 to 17） d and the platelet recovery 〉20× 10^9/L was 15 （12 to 27） d after transplantation. In 15 patients, short tandem repeat polymerase chain reaction （STR-PCR） confirmed that the donor cells were fully implanted on day 30. Transplant-related complications were acute graft-versus-host disease （aGVHD） in 6 patients （40%） （2 patients with aGVHD = grade Ⅰ , 4 patients with aGVHD = gradeⅡ , and none with aGVHD = grade Ⅲ-Ⅳ ）, chronic graft-versus-host disease （cGVHD） in 8 patients （53.3%） （2 cases of extensive-type, and 6 cases of limited-type）, hemorrhagic cystitis in 3 patients （20%）, and infected cytomegalovirus in 4 patients （26.7%）. There was no other serious complication. All patients were followed up for a median time of 15.4 months （ranging from 6 to 30）. One patient （6.7%） died of side effect related to the conditional regimen. Two patients （ 13.3% ） got recurrence, and the rest （ 80.0% ） survived event-free for 4 to 30 months. Conclusion After treated with reduced intensity Bu＋ Cy conditioning regimen-HSCT, leukemia patients have a better hematopoietic reconstitution and less transplant-related complications. It is also suggested that the pre-conditioning regimen has a low recurrence rate and a lower mortality. Therefore, this method maybe one of the safe and effective treatments for leukemia.