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目的 观察bcr/abl反义寡核苷酸 (AS ODN)净化后自体骨髓移植 (ABMT)治疗慢性粒细胞白血病 (CML)的疗效。方法 5例CML中慢性期 2例 ,加速期 1例 ,急变期 2例 ,均具b3a2型bcr/ablmRNA。骨髓采集前患者均经 2个疗程大剂量联合化疗的体内净化 ,自体骨髓经CS30 0 0plus浓集后加入 18bp的硫代bcr/ablAS ODN(40~ 6 0 μg/ml,48~ 6 0h)体外净化Ph+ 细胞。预处理方案为全身照射 +环磷酰胺 (TBI+CTX)或马法兰、阿糖胞苷、CTX和环己亚硝脲 (MAC +CCNU)。结果 体内净化后骨髓Ph+ 细胞减至 34 % (2 4%~ 46 % ) ,bcr/ablmRNA(+)的CFU GM减至 45 .6 % (33%~ 5 8% )。经bcr/ablAS ODN净化后 ,2例骨髓bcr/ablmRNA(- ) ,3例bcr/ablmRNA(+) ,但bcr/ablmRNA(+)的CFU GM明显减少。 5例ABMT后造血重建有延迟现象。经 2年以上随访观察 ,3例移植后持续 9~ 12个月主要遗传学缓解 (MCR) ,且移植后慢性期明显延长 ,其中 1例急变期患者至今无须治疗 ,现已无病生存 37个月 ,bcr/ablmRNA(- )。 1例急变期患者仅获短暂MCR ,移植后 7个月急变期复发 ,1例移植后第 74天因造血重建延迟而感染、出血死亡。结论 bcr/ablAS ODN净化后ABMT可使部分患者取得相当一段时期的MCR及延长慢性期。
Objective To observe the curative effect of autologous bone marrow transplantation (ABMT) treated with bcr / abl antisense oligonucleotide (AS ODN) in the treatment of chronic myeloid leukemia (CML). Methods Five cases of chronic phase CML in 2 cases, 1 case of accelerated phase, 2 cases of blast crisis, with b3a2 type bcr / ablmRNA. Patients before bone marrow harvesting were both treated with high-dose chemotherapy combined with 2 courses of chemotherapy. The autologous bone marrow was enriched with CS30 0plus and then added with 18bp thio-bcr / ablAS ODN (40-600 μg / ml, 48-60h) in vitro Purify Ph + cells. The pretreatment regimen was systemic irradiation with cyclophosphamide (TBI + CTX) or melphalan, cytarabine, CTX and macrolide (MAC + CCNU). Results In vivo, the percentage of bone marrow Ph + cells was reduced to 34% (2-4% ~ 46%) and the CFU GM of bcr / ablmRNA (+) was reduced to 45.6% (33% ~ 58%). After bcr / ablAS ODN purification, bcr / ablmRNA (-) and bcr / ablmRNA (+) were detected in 2 cases and CFU GM in bcr / ablmRNA (+). Delayed hematopoietic reconstitution occurred in 5 cases of ABMT. After 2 years of follow-up, 3 patients had sustained major remission (MCR) 9 to 12 months after transplantation and their chronic phase was significantly prolonged after transplantation. One of the patients with acute phase has no need for treatment up to now and has survived 37 Month, bcr / ablmRNA (-). Only one short-term MCR was found in 1 case of acute phase, and relapsed in 7 months after acute phase of transplantation. One case died of hematopoietic reconstitution on day 74 after hemorrhage. Conclusions After bcr / ablAS ODN purification, ABMT can make part of patients get MCR for a long time and prolong the chronic phase.