挽救性异基因造血干细胞移植治疗45例复发难治性急性髓系白血病疗效分析

Salvaged allogeneic hematopoietic stem cell transplantation for refractory/recurrent acute myeloid leukemia

目的分析复发难治性急性髓系白血病（AML）挽救性异基因造血干细胞移植（allo—HSCT）的疗效。方法2006年9月至2010年4月共完成45例复发难治性AML挽救性allo—HSCT，预处理前骨髓中幼稚细胞中位数为0．360（0．200～0．920）。供者来源：同胞HLA配型6／6相合移植6例，非血缘关系移植9例，单倍体移植30例。预处理方案：改良BuCy（白消安＋环磷酰胺）方案20例，大剂量阿糖胞苷（HDAra—C）＋Bu／氟达拉滨（Flu）16例，FLAG／RICBuCy方案6例，全身照射（TBI）／Cy2例，TBI／FIu方案1例，根据患者病情可加入G—CSF、甲氨蝶呤、米托葸醌、替尼泊苷、阿克拉霉素、赛替哌等药物。结果43例患者稳定植活，1例于植活前死于多器官衰竭。1例植入失败复发，白细胞植活中位时间为14（10～21）d，血小板植活中位时间为15（9～79）d。20例患者发生急性移植物抗宿主病（GVHD），累计发生率为53．3％，其中Ⅱ～Ⅳ度累计发生率为34％。26例患者发生慢性GVHD，慢性GVHD的累计发生率为59．1％，其中广泛型GVHD的累计发生率为38．3％。发生CMV血症28例，细菌感染33例，真菌感染16例。11例患者复发，其中9例为血液学复发，1例为免疫学复发，1例为中枢神经系统复发，累计复发率为29．2％。中位随访时间为30（0．5～57）个月，45例患者中29例存活，3年总存活率及无病存活率分别为62．6％及60．2％。结论个体化预处理方案联合预防性的免疫治疗进行allo．HSCT是治疗复发难治AML有效可靠的手段。

Objective To evaluate the efficacy of salvaged allogeneic hematopoietic stem cell trans- plantation （allo-HSCT） for refractory/recurrent acute myeloid leukemia （AML）. Methods A total of 45 pa- tients with refractory/recurrent AML were enrolled from September 2006 to April 2010. The median blasts in bone marrow （BM） were 36% （20% to 92% ） before conditioning. The donors were identical siblings （6） or unrelated ones （9） or haploidentical family members （30）. Conditioning regiments were individualized ac- cording to patients＇status, the regimen with high-dose cytarabine plus BuCy/CY was mostly used （20）. The patients with impaired organ function received above regimen except using fludarabine instead of cyclophos- phamide （16）. FLAG followed by reduced-intensified BuCy was employed for the recipients with more than 40% blasts in BM （6） to reduce leukemia burden. TBI/CY or TBI/Fludarabine was used for the recipients with extramedullary infiltration of leukemia or muhidmg resistant leukemia. G-CSF, MTX, NVT, Vm26, Acla or Thaltipa was added into conditioning regiments according to leukemia character. Results All but 2 patients attained durable engraftment. The incidence of grade U to IV aGVHD and cGVHD were 34% , 59.1% , respectively. With median follow-up 30 （0.5 -57） months, the relapse rate was 29.2%. Twenty- nine of 45 （60.2%） patients remained in complete remission since salvaged HSCT. Three-years disease-free survival and overall survival were 60.2% and 62.6%, respectively. Conclusion Our results indicated that the combination of salvaged HSCT with prophylactic immunotherapy might be a promising modality for treatment of refractory/recurrent AML, even with high leukemia burden.