马利兰﹢氟达拉滨预处理异基因造血干细胞移植治疗白血病的临床研究

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。

Clinical research of allogeneic hematopoietic stem cell transplantation using conditioning regimen with fludarabine and busulfan for leukemia

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.