采用白消安联合增量氟达拉滨预处理的allo-HSCT治疗中高危髓系白血病111例

Busulfan combined with increased-dose of fludarabine as conditioning regimen for allogeneic stem cell transplantation in intermediate and high-risk acute myeloid leukemia

目的探讨白消安联合增量氟达拉滨预处理方案进行异基因造血干细胞移植（allo-HSCT）治疗中高危髓系白血病的疗效与安全性。方法回顾性分析111例接受allo-HSCT的中高危髓系白血病患者的临床资料，预处理方案包括阿糖胞苷＋白消安＋氟达拉滨，氟达拉滨的总剂量为200mg／m^2，分为5～8d静脉输注。其中半相合移植或无关供者移植受者加用抗胸腺细胞球蛋白（ATG），ATG的总剂量为7．5～10mg／kg，分为4d静脉输注。应用环孢素A＋吗替麦考酚酯联合短程甲氨蝶呤进行移植物抗宿主病（GVHD）的预防。结果中性粒细胞和血小板累积植入率分别为100％和98．2％，植入时间中位数分别为13d（9～31d）和16d（8～75d）。Ⅱ～Ⅳ度和Ⅲ～Ⅳ度急性GVHD的累积发生率分别为39．6％和10．3％。在生存期超过3个月的受者中，慢性GVHD和广泛型慢性GVHD的累积发生率分别为21．0％和6．9％。其他合并症包括出血性膀胱炎的累积发生率为17．1％，无肝静脉阻塞病的发生。111例患者的3年总体存活率（0S）为78．8％，3年长期无病生存（DFS）为77．6％，其中疾病稳定期受者3年OS为88．6％，进展期受者3年OS为61．2％（P=0．001）。累积复发率为18．3％，其中疾病稳定期患者为7．3％，进展期患者为36．3％（P〈0．001）。结论白消安联合增量氟达拉滨（200mg／m^2）的清髓性预处理方案可以达到造血干细胞的稳定植入，移植相关并发症少，存活率高，可作为中高危髓系白血病预处理的一种有效选择。

Objective To analyze the efficacy and safety of conditioning regimen with busulfan and increased-dose of fludarabine for allogenetic hematopoietic stem cell transplantation （allo-HSCT） in intermediate and high- risk myeloid leukemia. Methods A total of 111 cases of intermediate and high-risk myeloid leukemia receiving allo-HSCT from Jan. 2007 to Dec. 2015 were retrospectively analyzed. Conditioning regimen consisted of busulfan （4 mg/kg, day orally or 3. 2 mg/kg, day intravenously for 3 days） with total dose of 200 mg/m2 fludarabine （by intravenous infusion, divided into 5-8 days）. For patients with unrelated and mismatched related donors, total dose of 7. 5-10 rag/ kg rabbit antithymocyte globulin （by intravenous infusion, divided into 4 days） was added to the conditioning regimen. GVHD prophylaxis consisted of cyclosporine A, short-term MTX and mycophenolatemofetial （MMF）. Results Neutrophil with ANC 〉0. 5 × 10^9/L was achieved in 100% of recipients with median time of 13 days （range： 9-31 days） and platelet 〉20× 10^9/L in 98. 2% of recipients after a median of 16 clays （range： 8-75 days）. The cumulative incidence of grade Ⅱ to aGVHD was 39. 6% and that of grade Ⅲ to Ⅳ aGVHD was 10. 3%, and overall cGVHD was 21.0% with extensive cGVHD being apparent in 6. 9%. The other complication included hemorrhagic cystitis （17. 1%） and no hepatic veno-occlusive disease （VOD） was diagnosed. For all patients, 3-year overall survival （OS） and 3-year disease-free survival （DFS） was 78. 8% and 77. 6% respectively. For patients with complete remission, the 3-year OS was 88. 6%, which was compared to that of 61.2% with advanced diseases （P = 0. 001）. The overall cumulative rate of relapse was 18. 3% with 7. 3% for stable disease and 36. 2% for advanced diseases （P〈0. 001）. Conclusion Busulfan combined with increased-dose of fludarabine as conditioning regimen for allo-HSCT in AML patients can achieve stably hematopoietic reconstruction, has low toxicities and survival advantage. Such regimen can be used for transplantation in intermediate and high-risk myeloid leukemia and particularly recommended for patients with stable disease.