Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, 49100, Petah-Tikva, Israel.
Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Ann Hematol. 2020 Dec;99(12):2939-2945. doi: 10.1007/s00277-020-04232-x. Epub 2020 Sep 6.
Sequential protocols combining salvage chemotherapy with reduced intensity conditioning (RIC) and allogeneic hematopoietic cell transplantation (alloHCT) for high-risk acute myeloid leukemia (AML) have been studied more than a decade. Purpose of this retrospective analysis was to evaluate the anti-leukemic efficacy and toxicity of FLAG-IDA protocol (fludarabine, cytarabine, and idarubicin) followed by treosulfan-based conditioning for patients with active AML. From January 2014 to November 2019, a total of 29 active AML patients [median age, 64 years (range, 23-73)] were treated. All patients completed protocol regimen and were transplanted. Five patients (17%) had grade 3-4 toxicities; therefore, treosulfan was substituted with total body irradiation (TBI) non-myeloablative conditioning. Six (20%) patients died within 30 post-transplant days, all from infectious complications. Out of 23 evaluable patients on day 30, 22 (96%) achieved complete hematologic remission with full donor chimerism. Non-relapse mortality (NRM) rates at 1 and 3 years were 22% and 49%, respectively. Median overall survival (OS) was 12 (95% CI, 4-20) months. OS and disease-free survival were 50% and 46% at 1 year and 28% and 17% at 2 years, respectively. Age, gender, disease burden, number of previous lines, and comorbidity score did not predict survival. Sequential strategy combining FLAG-IDA and treosulfan may offer a salvage option for few selected patients with active AML; however, high NRM presents a major obstacle to treatment success. Future efforts should focus on reducing NRM by moderating regimen intensity and by better selection of patients.
十余年来，人们一直在研究将挽救性化疗与强度降低的调理（RIC）和同种异体造血细胞移植（alloHCT）相结合的序贯方案，用于治疗高危急性髓系白血病（AML）。本回顾性分析的目的是评估 FLAG-IDA 方案（氟达拉滨、阿糖胞苷和伊达比星）继之以基于三氟尿苷的调理后用于活动性 AML 患者的抗白血病疗效和毒性。2014 年 1 月至 2019 年 11 月，共治疗了 29 例活动性 AML 患者[中位年龄 64 岁（范围 23-73）]。所有患者均完成了方案治疗并接受了移植。5 例（17%）发生 3-4 级毒性；因此，用全身照射（TBI）非清髓性调理替代了三氟尿苷。6 例（20%）患者在移植后 30 天内死亡，均死于感染性并发症。23 例可评估的患者中，有 22 例（96%）在第 30 天达到完全血液学缓解，均为完全供者嵌合。1 年和 3 年的非复发死亡率（NRM）分别为 22%和 49%。中位总生存期（OS）为 12 个月（95%CI，4-20）。1 年时 OS 和无病生存期分别为 50%和 46%，2 年时分别为 28%和 17%。年龄、性别、疾病负担、既往治疗线数和合并症评分均不能预测生存。FLAG-IDA 和三氟尿苷的序贯策略可能为少数选定的活动性 AML 患者提供一种挽救选择；然而，高 NRM 是治疗成功的主要障碍。未来的努力应侧重于通过降低方案强度和更好地选择患者来降低 NRM。
