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.doc

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陈 姝，李 文，罗 云，周 慷，张 颖，陈 林， 邓建川，娄世锋 （400010 重庆，重庆医科大学附属第二医院血液科）[摘要] 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>0.5×10 9/L的中位时间12（10～17）d，血小板>20×10 9/L的中位时间15（12～27）d30 d行短串联重复序列复合扩增检测(STR-PCR)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%）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[关键词] 白血病；异基因造血干细胞移植；预处理方案[中图法分类号] [文献标志码] ATherapeutic Effect effect of Aallogeneic Hhematopoietie Sstem Ccell Ttransplantation with Rreduced-intensity Cconditioning rRegimen of Bu/Cy for Patients with Lleukemia Chen Shu, Li Wen, Luo Yun, Zhou Kang, Zhang Ying, Chen Lin, Deng Jianchuan, Lou Shifeng (Department of Hematology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China)[Abstract] Objective tTo evaluate the observe the clinical value of allogeneic hematopoietic stem cell transplantation (Allo-Hsct) with Rreduced intensity Bu/Cy conditioning regimen in the treatment of patients with leukemia .Methods The Rreduced intensity BuCy conditioning regimen including busulfan (BU) 4 mg/(kg.·d) , for 3 d; Ccyclophosphamide (CY) 50 mg/(kg·.d), for 2 d., Aantithymocyte globulin (ATG) 2.5 mg/(kg·.d), for 2/4 d, were used forin 15 Lleukemia patients who underwent Allo-Hsct in our department from April 2010 to March 2012allogeneic hematopoietic stem cell transplantation. There were 2 cases of Aacute lymphocytic leukemia ., 3 cases of Aacute non-lymphoid leukemia , 9 cases of Cchronic myeloid leukemia , and 1 case of Crisis phase of CML,were included. Results (1)Hematopoietic reconstruction: All patients achieved successful hemopoietic reconstruction. The median time of the neutrophil recovery > 0.5×109/L was 12 (ranging 10- to 17) days and the platelet recovery >20×109 /L was 15 (12 -to 27) days after transplantation. In 15 patients, Sshort tandem repeat polymerase chain reaction (STR-PCR) confirmed that the donor cells wasere fully implanted on day +30. (2)Transplant-related complications: were acute graft-versus-host disease (aGVHD) in 6 patients (40%) developed Acute graft-versus-host disease (aGVHD), (among them,there were 2 cases of I。

, 4 cases of II aGVHD, and no of III-IV aGVHD);, chronic graft-versus-host disease (cGVHD) in 8 patients (53.3%) developed Chronic graft-versus-host disease (cGVHD), among them,there were (2 cases of Eextensive-type , and 6 cases of Llimited-type), cGVHD; hemorrhagic cystitis in 3 patients (20%) occurred hemorrhagic cystitis, and infected cytomegalovirus in 4 patients (26.7%)infected cytomegalovirus,. There was but no other serious complications. (3)Recurrence and survival:All patients were followed up for a median time of 15.4 months (ranging 6- to 30) months. 1One patient (6.7%) died of side effects related to the conditional regimen. 2Two patients (13.3%) got recurrence, , and the rest (80%) survived event-free for (4- to 30) months. Conclusion After treated with Reduced reduced intensity Bu/Cy conditioning regimen-HSCT, leukemia patients with Leukemia have a better hematopoietic reconstitution and less transplant-related complications;. It was 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。

[Key words] leukemia; allogeneic hematopoietic stem cell transplantation; conditioning regimenCorresponding author: Lou Shifeng, E-mail: loushifeng@[通信作者] 娄世锋,E-mail: loushifeng@异基因造血干细胞移植(allo-HSCT)仍是目前根治白血病最有效的手段 [1],其预处理方案是重要环节传统预处理方案中，马利兰起主要清髓作用，用量为4 mg/（kg·d）×4 d，一般认为低于4 mg/（kg·d）×2 d则为非清髓剂量大剂量马利兰也是导致肝静脉阻塞综合征等严重移植并发症的主要原因传统预处理方案 [2]已应用多年，虽疗效可靠，但毒副反应显著，移植相关死亡率高；非清髓性预处理方案大大降低了毒性和移植相关死亡率，但由于杀灭白血病细胞效应减弱，白血病复发率升高 [3]，致患者总体生存率并未显著改善近年来，介于清髓与非清髓移植之间的减低剂量预处理方案 [4]逐渐受到关注减低预处理强度可降低放化疗毒性,减少骨髓抑制的时间,但因其强度仍高于传统非清髓方案,故能相对充分地杀灭肿瘤细胞,同时也保留移植物抗肿瘤效应（GVL） [5],可望在降低毒副反应的同时能减少复发，提高患者总体生存率。

我院2010年4月至2012年3月采用减低剂量Bu/Cy预处理方案行allo-HSCT治疗白血病15例，其清髓强度介于传统清髓与非清髓之间，即将马利兰剂量改为4 mg/（kg·d）×3 d，初步观察表明，该预处理方案可在减轻预处理毒性同时减少白血病复发，值得进一步研究1 资料与方法1.1 观察对象2010年4月至2012年3月我科收治白血病患者15例，包括男性7例,女性8例,年龄17～48岁,中位年龄32岁其中慢性粒细胞白血病(chronic myeloid leukemia，CML)10例，慢性期(CP)9例,急变期（BP)1例；急性淋巴细胞白血病(acute lymphoblastic leukemia，ALL) CR1 2例,急性髓系白血病未分化型(AML-M1)PR 1例,急性粒细胞白血病部分分化型(AML-M2)CR1 2例其中行无关供者造血干细胞移植7例（6例HLA全相合,1例HLA 8/10个位点相合,1个Cw和1个DQ位点不合），同胞供者8例（6例HLA全相合,2例HLA 5/6个位点相合，均为1个HLA-A位点不合）供受者均签署知情同意书，临床观察经医院医学伦理委员会批准。

1.2 预处理方案减低剂量Bu/Cy预处理方案：15例白血病患者均采用马利兰+环磷酰胺+ATG预处理方案:马利兰4 mg/（kg·d），3 d（移植前6、5、4 d），口服；环磷酰胺50 mg/（kg·d），2 d（移植前3、2 d），静脉滴注根据供受者HLA位点不合情况用兔抗胸腺。