强化预处理allo—HSCT联合伊马替尼治疗费城染色体阳性ALL八例

Combined intensive preconditioning regimen allo-HSCT with imatinib for treatment of Ph chromosome positive acute lymphocyte leukemia

目的总结强化预处理异基因造血干细胞移植（allo-HSCT）联合伊马替尼治疗费城染色体阳性（Ph^＋）急性淋巴细胞白血病（ALL）的经验。方法接受同胞allo-HSCT的Ph^＋ALL患者8例，移植前均达完全缓解（CR），其中5例在移植前后使用伊马替尼，3例未使用。8例中，7例采用以白消安＋环磷酰胺（BuCy2）为基础的增强预处理方案，1例采用全身放疗（TBI）＋Cy的增强预处理方案。患者输注单个核细胞的中位数为6．02×10^8／kg，输注的CD34^＋细胞的中位数为3．14×10^6／kg。术后采用环孢素A（CsA）及甲氨蝶呤（MTX）预防移植物抗宿主病（GVHD）。结果allo-HSCT后所有患者均达到白细胞植入和血小板植入，白细胞植入时间中位数为15．5d，血小板植入时间中位数为19d；allo-HSCT后30d，8例患者经检测均为完全供者型。患者对预处理方案的耐受性良好，未发生严重预处理相关并发症。8例患者中，4例患者发生急性GVHD，其中Ⅰ度2例，Ⅱ度1例，Ⅳ度1例。7例存活100d以上的患者中，3例发生慢性GVHD。随访结束时共6例患者存活，其中3例无白血病存活，3例复发。死亡2例，1例死于原发病复发，1例死于急性GVHD。结论强化预处理allo-HSCT联合伊马替尼是治疗Ph^＋ALL的有效方法，但在应用过程中应注意伊马替尼的抗慢性GVHD作用。

Objective To evaluate the outcome of combination of intensive preconditioning regimen allo-HSCT with imatinib for treatment of Ph chromosome positive acute lymphocyte leukemia （ALL）. Methods Betweeja 2009 and 2010, 8 patients diagnosed as Ph^＋ ALL received allo-HSCT from HLA identical sibling during complete remission. Imatinib was added into the therapies of 5 patients. Seven patients received the intensive preconditioning regimen based on BuCy2, one patient received the regimen of TBI-Cy. A median of 6. 02 ×10^8/kg mononuclear cells and 3. 14 × 10^6/kg CD34^＋ cells were transfused. GVHD prophylaxis included cyclosporine A and methotrexate. Results All patients were well tolerant to the regimen without serious regimen-related toxicity. The median time of ANC≥0. 5× 10^9/L was 15.5 days, and that of PLT≥20 × 10^9/L was 19 days. Thirty days after allo-HSCT, all patients got donor engraftment successfully. Among 8 cases, 4 cases presented acute GVHD, 2 developed degree Ⅰ, one developed degree Ⅱ , and one developed degree Ⅳ. Seven patients were alive 100 days after allo-HSCT, 3 of whom presented chronic GVHD. At the end of following-up period, 6 patients were alive, among them, 3 patients were alive without relapsel 3 patients relapsed; Two patients died, one from acute GVHD, and one from leukemia relapse. Conclusion Combined intensive preconditioning regimen allo-HSCT with Imatinib was an effective treatment for Ph^＋ ALL, but the effect of anti-chronic GVHD of imatinib should arouse certain attention.