Medical Faculty, Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany.
Leukemia. 2013 Jun;27(6):1229-35. doi: 10.1038/leu.2013.7. Epub 2013 Jan 14.
The combination of azacitidine and donor lymphocyte infusions (DLI) as first salvage therapy for relapse after allogeneic transplantation (allo-HSCT) was studied in 30 patients with acute myeloid leukemia (AML; n=28) or myelodysplastic syndromes (MDS; n=2) within a prospective single-arm multicenter phase-II trial. Treatment schedule contained up to eight cycles azacitidine (100 mg/m(2)/day, days 1-5, every 28 days) followed by DLI (from 1-5 × 10(6) to 1-5 × 10(8) CD3(+)cells/kg) after every second azacitidine cycle. A median of three courses azacitidine (range 1-8) were administered, and 22 patients (73%) received DLI. Overall response rate was 30%, including seven complete remissions (CRs, 23%) and two partial remissions (7%). Five patients remain in CR for a median of 777 days (range 461-888). Patients with MDS or AML with myelodysplasia-related changes were more likely to respond (P=0.011), and a lower blast count (P=0.039) as well as high-risk cytogenetics (P=0.035) correlated with the likelihood to achieve CR. Incidence of acute and chronic graft-versus-host disease was 37% and 17%, respectively. Neutropenia and thrombocytopenia grade III/IV occurred during 65% and 63% of treatment cycles, while infections were the most common grade III/IV non-hematological toxicity. Azacitidine and DLI as salvage therapy is safe, induces long-term remissions and may become an alternative for patients with AML or MDS relapsing after allo-HSCT.
在一项前瞻性单臂多中心 II 期试验中，对 30 例异基因造血干细胞移植（allo-HSCT）后复发的急性髓系白血病（AML；n=28）或骨髓增生异常综合征（MDS；n=2）患者进行了阿扎胞苷联合供者淋巴细胞输注（DLI）作为一线挽救治疗的研究。治疗方案包括最多 8 个周期的阿扎胞苷（100mg/m2/天，第 1-5 天，每 28 天），然后在每两个阿扎胞苷周期后进行 DLI（1-5×106 至 1-5×108 CD3+细胞/kg）。中位数为 3 个疗程的阿扎胞苷（范围 1-8），22 例（73%）患者接受了 DLI。总体缓解率为 30%，包括 7 例完全缓解（CR，23%）和 2 例部分缓解（7%）。5 例患者的 CR 中位数为 777 天（范围 461-888）。MDS 或伴有 MDS 相关改变的 AML 患者更有可能有反应（P=0.011），较低的原始细胞计数（P=0.039）和高危细胞遗传学（P=0.035）与获得 CR 的可能性相关。急性和慢性移植物抗宿主病的发生率分别为 37%和 17%。中性粒细胞减少和血小板减少 III/IV 级分别发生在 65%和 63%的治疗周期中，而感染是最常见的 III/IV 级非血液学毒性。阿扎胞苷和 DLI 作为挽救治疗是安全的，可诱导长期缓解，可能成为 allo-HSCT 后复发的 AML 或 MDS 患者的替代治疗方法。
