Dyakonova Y Y, Bydanov O I, Popov A M, Olshanskaya Y V, Boichenko E G, Aleynikova O V, Maschan M A, Shelikhova L N, Litvinov D V, Khachatryan L A, Ponomareva N I, Fechina L G, Novichkova G A, Pashanov E D, Karachunskiy A I
Dmitry Rogachev National Research Center for Pediatric Hematology, Oncology, and Immunology, Moscow, Russia.
Республиканский Republican Scientific and Practical Center for Pediatric Oncology, Hematology, and Immunology, Minsk, Republic of Belarus.
Ter Arkh. 2018 Aug 17;90(7):38-50. doi: 10.26442/terarkh201890738-50.
The analysis of experience of nelarabine use in refractory/relapsed T-cell acute lymphoblastic leukemia (T-ALL) depending on the immunophenotype and the line of therapy.
All the patients with relapsed or refractory T-ALL aged from 0 to 18 years who received treatment with nelarabine as a part of the therapeutic element R6 were included in the study. For all patients a detailed immunological analysis of leukemia cells with discrimination of immunological variants TI, TII, TIII or TIV was performed. Patients administered with nelarabine as a first therapeutic element were referred to the first-line therapy group, other patients were referred to the second-line therapy group. Nelarabine was ad- ministered as intravenous infusion at a dose of 650 mg/m2, on days 1-5. Allogeneic hematopoietic stem cells transplantation (allo-HSCT) was considered for all patients.
From 2009 to 2017, 54 patients with refractory/relapsed T-ALL were treated with nelarabine. Five-year event-free survival (EFS) and overall survival (OS) was 28% for all patients, cumulative risk of relapse (CIR) was 27%. EFS was significantly higher in nelarabine first-line therapy group in comparison with second-line therapy group (34±8% vs 8±8%, p=0,05). In patients after allo-HSCT EFS, OS and CIR were 51±10%, 50±10% and 39,1±9,5% accordingly. The best results were achieved in patients with TI immunophenotype. No toxicity-related mortality as well as severe neurologic complications or discontinuation of therapy associated with use of nelarabine were reported.
The use of nelarabine is an effective strategy for the treatment of relapsed and refractory T-ALL. The best treatment outcomes were obtained in patients with TI immunophenotype and in the first-line therapy group. Optimal dosage regimens can be established dur- ing controlled clinical trials.
根据免疫表型和治疗线数分析奈拉滨在难治性/复发性T细胞急性淋巴细胞白血病（T-ALL）中的应用经验。
本研究纳入了所有0至18岁复发或难治性T-ALL患者，这些患者接受了作为治疗方案R6一部分的奈拉滨治疗。对所有患者的白血病细胞进行了详细的免疫分析，区分了免疫变体TI、TII、TIII或TIV。接受奈拉滨作为首个治疗方案的患者被归入一线治疗组，其他患者被归入二线治疗组。奈拉滨以650mg/m²的剂量在第1 - 5天静脉输注。所有患者均考虑进行异基因造血干细胞移植（allo-HSCT）。
2009年至2017年，54例难治性/复发性T-ALL患者接受了奈拉滨治疗。所有患者的5年无事件生存率（EFS）和总生存率（OS）为28%，累积复发风险（CIR）为27%。奈拉滨一线治疗组的EFS显著高于二线治疗组（34±8%对8±8%，p = 0.05）。allo-HSCT后的患者中，EFS、OS和CIR分别为51±10%、50±10%和39.1±9.5%。TI免疫表型的患者取得了最佳结果。未报告与毒性相关的死亡以及与使用奈拉滨相关的严重神经并发症或治疗中断情况。
使用奈拉滨是治疗复发和难治性T-ALL的有效策略。TI免疫表型的患者和一线治疗组取得了最佳治疗效果。可在对照临床试验中确定最佳给药方案。
