高通量药敏检测技术在儿童复发难治性急性白血病中的应用

Application of high-throughput drug sensitivity testing in children with relapsed and refractory acute leukemia

摘要:

目的 探究高通量药敏（high-throughput drug sensitivity, HDS）检测技术在儿童复发难治性急性白血病（relapsed and refractory acute 1eukermia, RR-AL）的应用现状及分析挽救治疗方案的可行性。方法 回顾性收集2021年11月—2023年10月郑州大学第一附属医院儿童血液与肿瘤科行HDS检测的RR-AL患儿的临床资料，并对药敏结果及治疗结局进行分析。结果 17例RR-AL患儿接受HDS检测，复发难治性急性髓系白血病7例（41%），复发难治性急性淋巴细胞白血病10例（59%）。高度敏感化疗药物/方案的检出率为53%（9/17），中度敏感化疗药物/方案的检出率为100%（17/17）。17例RR-AL患儿高度敏感度和中度敏感度化疗药物及方案中，MOACD方案（米托蒽醌+长春新碱+阿糖胞苷+环磷酰胺+地塞米松）占比100%，单药米托蒽醌抑制率最高（94%，16/17），靶向药抑制率最高为硼替佐米（94%，16/17）。9例患儿根据HDS结果调整化疗，行造血干细胞移植4例；无病生存4例，死亡5例。8例经验化疗，行造血干细胞移植2例；无病生存4例，死亡4例。结论 HDS检测技术可为儿童RR-AL筛选出高度敏感药物/方案，提高再次缓解率，为后续进行造血干细胞移植创造条件。

Abstract:

Objective To explore the current application of high-throughput drug sensitivity (HDS) testing in children with relapsed and refractory acute leukemia (RR-AL) and analyze the feasibility of salvage treatment plans.Methods A retrospective collection of clinical data from children with RR-AL who underwent HDS testing at the Department of Children's Hematology and Oncology of the First Affiliated Hospital of Zhengzhou University from November 2021 to October 2023 was conducted, followed by an analysis of drug sensitivity results and treatment outcomes.Results A total of 17 children with RR-AL underwent HDS testing, including 7 cases of relapsed refractory acute myeloid leukemia and 10 cases of relapsed refractory acute lymphoblastic leukemia. The detection rate of highly sensitive chemotherapy drugs/regimens was 53% (9/17), while the detection rate of moderately sensitive chemotherapy drugs/regimens was 100% (17/17). Among the 17 RR-AL patients with highly and moderately sensitive chemotherapy drugs and regimens, the MOACD regimen (mitoxantrone + vincristine + cytarabine + cyclophosphamide + dexamethasone) accounted for 100%, with the highest inhibition rate for single-agent mitoxantrone (94%, 16/17), and the highest inhibition rate for targeted therapy being bortezomib (94%, 16/17). Nine patients adjusted their chemotherapy based on HDS testing results, with 4 undergoing hematopoietic stem cell transplantation. Four patients achieved disease-free survival, while 5 died. Eight patients received empirical chemotherapy, with 2 undergoing hematopoietic stem cell transplantation; 4 achieved disease-free survival, while 4 died.Conclusions HDS testing can identify highly sensitive drugs/regimens for children with RR-AL, improving the rate of re-remission and creating conditions for subsequent hematopoietic stem cell transplantation.