白消安注射液预处理在异基因造血干细胞移植治疗恶性血液病中的效果

Outcome of intravenous busulfan-based conditioning prior to allogeneic hematopoietic stem cell transplantation for treating hematologic malignancies

背景:白消安/环磷酰胺是经典的非全身照射预处理方案,效果肯定,但白消安常为口服制剂,国内使用白消安注射液进行预处理相关报道较少。目的:观察含白消安注射液预处理方案进行异基因造血干细胞移植治疗恶性血液病的疗效和毒副作用。设计、时间及地点:临床观察实验,于2005-06/2008-01在华中科技大学同济医学院附属同济医院血液科完成。对象:24例恶性血液病患者,男12例,女12例,平均年龄29岁。方法:亲缘白细胞分化抗原全合的移植采用含白消安注射液的改良的白消安/环磷酰胺预处理方案:阿糖胞苷2～4g/(m2·d)×2d,白消安注射液3.2mg/(kg·d)×3d,环磷酰胺1.8g/(m2·d)×2d,司莫司汀250mg/(m2·d)×1d;亲缘白细胞分化抗原不合和非亲缘的移植在改良白消安/环磷酰胺方案基础上加用猪抗胸腺淋巴细胞球蛋白20mg/(kg·d)×4d或兔抗胸腺淋巴细胞球蛋白2.5mg/(kg·d)×4d。亲缘白细胞分化抗原全合移植13例,亲缘白细胞分化抗原不合移植6例,非亲缘移植5例。主要观察指标:移植后患者造血功能恢复时间、移植相关毒性、巨细胞病毒感染、移植物抗宿主病发生情况。结果:移植后30d所有患者行短串联重复序列检测均显示为完全供者的基因型。移植过程中2例患者出现轻度口腔黏膜炎,11例患者出现轻度胃肠道反应,5例患者出现轻度肝功能异常,无一例发生癫痫和肝静脉闭塞病。急性移植物抗宿主病发生率为33.3%,在可供评价的20例患者中,慢性移植物抗宿主病发生率为65.0%,其中广泛型3例。中位随访时间267d,17例患者无病生存,1例带病生存,6例死亡,存活病例仍在继续随访中。结论:本组患者的白消安注射液用法及用量保证了移植的成功,且无明显毒副作用。

BACKGROUND： Busulfan/cyclophosphamide is a classic conditioning regimen of non-total body irradiation. It is affirmative, but busnlfan is used to be oral pharmaceutics, and the reports correlated intravenous busulfan-based conditioning is less in China. OBJECTIVE： To explore the effect and toxic reactions of intravenous busulfan-based conditioning prior to allogeneic hematopoietic stem cell transplantation （allo-HSCT） for hematologic malignancies. DESIGN, TIME AND SETTING： The clinical experiment was performed at the Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from June 2005 to January 2008. PARTICIPANTS： Twenty-four patients with hematologic malignancies, 12 males and 12 females were enrolled in this study, averagely 29 years old. METHODS： Homologous leucocytic antigen matched sibling identical transplantation used intravenous busulfan-based modified conditioning, arabisylcytosin 2-4 g/（m^2 · d）×2 d, busulfan 3.2 mg/（kg · d）×3 d, cyclophosphamide 1.8 g/（m^2 · d）×2 d, semustine 250 mg/（m^2 · d）× 1 d. Homologous leucocytic antigen matched incompatible transplantation used intravenous busulfan-based modified conditioning, and combined with pig anti-thymic lymphocyte protein 20 mg/（kg · d） × 4 d or rabbit anti-thymic lymphocytes protein 2.5 mg/（kg · d） × 4 d. A total of 13 received sibing transplants, 6 received related mismatch transplants and 5 received unrelated transplants. MAIN OUTCOME MEASURES： Recovery of blood-producing function after transplantation, transplantation associated toxicity, cytomegalovirus infections and graft versus host disease RESULTS： The DNA fingerprinting showed engraftement in all 30 patients by short tandem repeated-polymerase chain reaction （STR-PCR） after transplantation. During conditioning, 2 had slight oral mucositis, 11 had slight vomiting, 5 had slight hepatic damage and none developed seizure and veno-occlusion disease. Acute graft versus host disease （aGVHD） occurred in 8 of 24 patients （33.3%）. In 20 patients with evaluation, the incidence of chronic graft versus host disease （cGVHD） was 65.0% （13/20）, in which extensive type occurred in 3 patients. All patients were followed-up for median 267 days after allo-HSCT, and 17 alive patients without relapse, 1 alive with relapse, 6 died. Living cases were still in follow-up. CONCLUSION： The usage and dosage of busulfan are suitable for obtaining success transplantation, and no significant toxic and side effects.