摘要
目的:探讨马利兰+氟达拉滨(Bu/Flu)预处理方案异基因造血干细胞移植治疗白血病的临床疗效。方法:30例患者中,急性淋巴细胞白血病(ALL)12例,急性髓系白血病(AML)12例,其中1例为MDS转化,慢性粒细胞白血病(CML)6例;其中急性白血病未缓解或复发状态下移植6例,CML加速期患者1例。供者干细胞为G-CSF动员后采集的HLA配型全相合或一个位点不合的同胞(21例)或非血缘(9例)外周血造血干细胞,有1例成人ALL患者接受HLA配型相合的双份脐带血移植。预处理方案包括:注射用马利兰3.2mg/(kg·d)×3-4d,氟达拉滨30mg/(m2·d)×4-6d,同胞不全相合和非血缘移植患者加用兔抗人胸腺细胞免疫球蛋白(ATG)2.5mg/(kg·d)×3d。输注外周血单个核细胞数7.73(0.36-16.0)×108/kg,CD34+造血干细胞数3.26(0.77-17.6)×106/kg。用环孢素+短疗程甲氨喋呤或环孢素+吗替麦考酚酯预防移植物抗宿主病(GVHD)。采用DNA短串联重复序列多态性(STR)分析方法鉴定供者干细胞植入情况。结果:29例患者重建造血,检测外周血白细胞STR-DNA证实均为100%完全供者植入,1例非血缘全相合患者未植入于短期内死亡外,其余患者为完全供者型,植入率为96.7%。血缘相关HSCT和非血缘相关HSCT白细胞植活的中位时间分别为11(8-17)d和13(9-15)d;血小板植活的中位时间分别为13(7-22)d和14(8-25)d。出现急性GVHD 14例,占46.7%,其中I-II度10例(33.3%),III-IV度者4例(13.3%);6例发生慢性局限性GVHD,发生率为20.0%。随访1-66个月(中位时间20个月),总体生存率(OS)为63.3%,无事件生存率(DFS)为51.7%。结论:Bu/Flu预处理方案移植治疗白血病相关并发症轻,有很好耐受性和较好疗效,是值得推广应用的预处理方案。
Objective:To discuss the clinical effect of fludarabine and busulfan conditioning regimen for allogeneic peripheral blood stem cell transplantation in leukemia patients. Methods:Of the 30 patients,12 were acute lympho-blastic leukemia( ALL),12 acute myeloid leukemia( AML),one acute myeloid leukemia transformed from myelodys-plastic syndrome(MDS),6 chronic myelogenous leukemia(CML). Donor's peripheral blood hematopoietic stem cells were collected after the G-CSF mobilized HLA matching or 1 point mismatched sibling(21 cases)or unrelated(9 cases). 1 adult ALL patient received HLA matching pair of umbilical cord blood transplantation. Conditioning regi-men:injected busulfan 3. 2mg/(kg·d)for 3 -4 days,fludarabine 30mg/(m2 ·d)for 4 -6 days,compatriot mis-matched and unrelated transplantation combined with rabbit anti-human thymocytes immune globulin(ATG)2. 5mg/(kg·d)for 3 days. Infusion of peripheral blood mononuclear cells(0. 36 -16. 0)× 108/kg(average 7. 73 × 108/kg),(0. 77 -17. 6)× 106/kg CD34﹢ hematopoietic stem cells( average 3. 26 × 106/kg). Cyclosporine ﹢ short course of methotrexate or CSA ﹢ mycophenolate mofetil were used to prevent graft-versus-host disease( GVHD). DNA sequencing of short tandem repeat polymorphism( STR)analysis method was performed for identification of do-nor stem cells implantation. Results:Twenty nine patients achieved hematopoiesis reconstitution with their full donor chimerisms confirmed by STR-DNA analysis,1 patient didn't achieve hematopoiesis reconstitution. No serious com-plications occurred. Neutrophil engraftment was at 8-17 days( median 11 days),platelet engraftment at 8-25 days (median 13 days). Acute GVHD occurred in 14 cases,accounting for 46. 7%,I-II degree aGVHD happened in 10 cases(30. 0%),III-IV degree aGVHD happened in 4 cases(16. 7%). Chronic GVHD occurred in 6 cases of 30 patients could be assessed,accounting for 20. 0%. 1-66 months of follow-up(median time 20 months)revealed the overall survival rate was 63. 3%,disease - free 51. 7%. Conclusion:Allo - HSCT by conditioning regimen with busulfan and fludarabine is low toxic,well tolerated and with better effect for leukemia patients. It is worthy of popu-larization and application.
出处
《现代肿瘤医学》
CAS
2014年第6期1430-1434,共5页
Journal of Modern Oncology
基金
西安交通大学医学院医院新技术新疗法项目(编号:2011073)
关键词
异基因造血干细胞移植
白血病
预处理
氟达拉滨
allogeneic hematopoietic stem cell transplantation
leukemia
conditioning regimen
fludarabine