亲缘异基因造血干细胞移植联合甲磺酸伊马替尼治疗Ph阳性白血病

Hematopoietic stem cell transplantation in combination with imatinib mesylate for treatment of Philadelphia-positive leukemia

背景:造血干细胞移植是可以治愈Ph+白血病有效方法,甲磺酸伊马替尼是一种高度特异的酪氨酸激酶抑制剂,能抑制BCR/ABL酪氨酸激酶活性,在Ph+白血病中的应用越来越多。目的:探讨甲磺酸伊马替尼联合亲缘异基因造血干细胞移植治疗Ph+白血病的临床疗效。方法:回顾性分析2011年1月至2012年10月采用亲缘异基因造血干细胞移植联合甲磺酸伊马替尼治疗12例Ph+白血病的疗效并文献复习。结果与结论:12例患者移植后均获得造血重建,移植后中性粒细胞和血小板植活的中位时间分别为15 d和18 d;发生Ⅱ度急性移植物抗宿主病7例,Ⅲ度急性移植物抗宿主病1例,局限型慢性移植物抗宿主病7例,广泛型慢性移植物抗宿主病3例;无白血病存活率为67%,移植相关死亡率为25%。行HLA匹配亲缘造血干细胞移植者的总体存活率为75.0%。平均无病生存8.5个月(7-17个月),BCR/ABL转阴时间2-5个月。亲缘异基因造血干细胞移植前、后联合甲磺酸伊马替尼治疗Ph+白血病,具有降低移植前白血病细胞负荷,抑制残留白血病细胞增殖,促进供者完全嵌合状态的转变,是一种安全有效的治疗方法。

BACKGROUND： Hematopoietic stem cell transplantation is recognized as the only method of curing Philadelphia-positive leukemia. Imatinib mesylate is a competitive inhibitor of the BCPJABL tyrosine kinase, which has been used more and more in the treatment of Philadelphia-positive leukemia. OBJECTIVE： To observe the curative effect of imatinib mesylate combined with allogeneic hematopoietic stem cell transplantation for treatment of Philadelphia-positive leukemia. METHODS： We retrospectively analyzed the clinical effect of 12 patients with Philadelphia-positive leukemia who were treated with the combined therapy of imatinib mesylate and allogeneic hematopoietic stem cell transplantation from January 2011 to October 2012, and reviewed the relevant literatures. RESULTS AND CONCLUSION： Hematopoietic recenstitution was achieved in all 12 patients and the median times of neutrophil recovery and platelet recovery were 15 and 18 days, respectively. Of the 12 patients, 7 patients developed acute graft-versus-host disease Ⅱ, 1 developed acute graft-versus-host disease III, 7 developed localized chronic graft-versus-host disease, and 3 developed extensive chronic graft-versus-host disease. Leukemia-free survival rate was 66.7%, and transplant-related mortality was 25.0%. The overall survival rate of HLA-matched sibling donors was 75.0%. The mean disease-free survival period was 8.5 months （7-17 months）, and the time needed for BCR/ABL becoming negative was 2-5 months. As an effective and safe method for PhUadelphia-positive leukemia, allogeneic hematopoietic stem cell transplantation combined with imatinib mesylate before and after transplantation reduces the leukemia cell load before transplantation, inhibits the proliferation of residual leukemia cells, and promotes full chimerism change.