Blinatumomab 治疗小儿急性淋巴细胞白血病:一个中心的经验

N. V. Muliarova, A. Smirnova, S. Lapaeva, Y. Toshina, Y. Dinikina
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引用次数: 0

摘要

背景。尽管在治疗 B 细胞急性淋巴细胞白血病(B-ALL)方面取得了成功,但克服标准化疗方案的毒性和治疗复发/难治性(r/r)白血病仍是当务之急。最有希望的方案是使用免疫疗法(IT),包括单克隆抗体 blinatumomab (BM)。研究目的分析 BM 在 V-ALL 儿童中的使用适应症、疗效和耐受性。材料与方法。自2016年4月至2024年1月,在阿尔马佐夫国立医学研究中心儿童肿瘤血液病和中医化疗科对B-ALL患儿使用BM的情况进行了回顾性评估。研究结果研究共纳入 53 名患者,包括 28 名女孩(53%)和 25 名男孩(47%),中位年龄为 7.7 岁(2.08-19.8 岁)。使用 BM 的适应症如下:(1) 原发性 ALL 患者巩固缓解(CR)(17 人,32%);(2) 在完成诱导化疗(CT)后或异基因造血干细胞移植(alloHSCT)阶段前,最小残留病(MRD)持续存在(23 人,43%);(3) 由于СT之前的毒性或其他禁忌症而替代标准CR(12人,23%);(4) r/r ALL的挽救治疗(1人,1.9%)。89%的病例在第一个IT疗程后达到了MRD阴性的缓解状态。对一名患有r/r ALL且骨髓完全被疱疹浸润的患者使用BM进行治疗是有效的,有助于在治疗的第15天将肿瘤数量减少到7.2%,但是,由于之前存在的严重感染的发生和发展,出现了致命的结果。最常见的III-IV级毒性变异是白细胞/中性粒细胞减少(28%)和神经毒性(3.7%)。有 19% 的患者需要减少 BM 剂量以缓解毒性,而减少剂量治疗的中位天数为 4 天。为此目的使用皮质类固醇的病例占 11%,使用抗菌疗法的病例占 13%。在结果评估时,研究组中没有出现复发病例。文章分析了在 B-ALL 患者中使用 BM 的国际经验。我们的经验和所提供的文献数据表明,BM 在 B-ALL 儿童患者中的适应症有了合理的扩展,而且疗效显著,毒性也令人满意。
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Blinatumomab in pediatric acute lymphoblastic leukemia: one center experience
Background. Despite the successes achieved in the treatment of B-cell acute lymphoblastic leukemia (B-ALL), overcoming the toxicity of standard chemotherapy regimens and the treatment of relapsed/refractory (r/r) forms of the disease remains relevant. The most promising option is to use immunotherapy (IT), including a monoclonal antibody blinatumomab (BM). The purpose of the study. To analyze indications of using, as well as efficacy and tolerability of BM in children with V-ALL. Materials and methods. From April 2016 to January 2024 a retrospective assessment of using of BM in children with B-ALL in the chemotherapy department of oncohematological diseases and TCM for children in Almazov National Medical Research Centre was performed. Results. The study included 53 patients, including 28 (53 %) girls and 25 (47 %) boys with median age of 7,7 (2,08–19,8) years. Indications for using of BM were as follows: (1) consolidation of remission (CR) with primary ALL (n = 17, 32 %); (2) persistence of minimal residual disease (MRD) (n = 23, 43 %) after completion of chemotherapy (CT) induction or before the stage of allogeneic haematopoietic stem cell transplantation (alloHSCT); (3) replacement of the standard CR due to the previous toxicity of СT or other contraindications to its implementation (n = 12, 23 %); (4) salvage therapy for r/r ALL (n = 1, 1,9 %). The status of MRD-negative remission after the 1st course of IT was achieved in 89 % of cases. Therapy using BM in a patient with the r/r ALL and total blast infiltration of the bone marrow was effective and facilitated reducing the tumor population to 7,2% by day 15 of therapy, however, there was a fatal outcome due to development and progression of preexisted severe infection. The most common variants of grade III–IV toxicity were leuko-/neutropenia (28 %) and neurotoxicity (3,7 %). BM dose reduction for the purpose of relieving toxicity was required in 19 % of patients, while the median days of therapy with dose reduction was 4. Corticosteroids were used for this purpose in 11 % of cases, antibacterial therapy — in 13 %. At the time of results evalution, there were no relapses of the disease in the study group. The article analyzes the international experience of using BM in patients with B-ALL.Conclusion. Our experience and the presented literature data demonstrate a reasonable expansion of indications for using of BM in children with B-ALL with high efficacy and satisfactory toxicity profile.
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