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费城染色体阳性急性淋巴细胞白血病的治疗

英文原题:Treatment of Philadelphia-Positive Acute Lymphoblastic Leukemia.

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Treatment of Philadelphia-Positive Acute Lymphoblastic Leukemia.

PubMed 2025/06/24(内容时间) Acta Haematol Q2 · IF 2.8(JCR 2025)

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研究概要

尽管 TKI 仍是治疗的基石,但免疫治疗策略的整合——包括双特异性抗体和 CAR-T 细胞疗法——已扩大了治疗选择,不仅在 R/R 背景下,而且越来越多地用于一线方案。旨在优化这些疗法的序贯、联合和持续时间的研究对于进一步提高临床结局至关重要。

研究思路结论见上方概要

费城染色体阳性急性淋巴细胞白血病历来与不良预后和有限治疗选择相关。然而,在过去20年中,治疗范式已显著转变。摘要:酪氨酸激酶抑制剂(TKIs),如伊马替尼、达沙替尼和普纳替尼的引入,已彻底改变了一线治疗,显著提高了缓解率和长期生存。这些药物与减低强度化疗或甚至与皮质类固醇联合使用时,已使毒性较低的方案成为可能,尤其对老年或不适合患者有益。可测量残留病监测的实施已成为风险分层和治疗决策的关键工具。因此,异基因造血干细胞移植,曾被视为治愈性治疗的基石,其在实现持续深度分子学缓解患者中的作用正在被重新评估。更近期,免疫治疗策略——包括双特异性T细胞衔接器博纳吐单抗和嵌合抗原受体(CAR)T细胞疗法——已作为常规化疗和TKIs的有效替代方案出现。

展开英文摘要原文

BACKGROUND: Philadelphia chromosome-positive acute lymphoblastic leukemia has historically been associated with poor prognosis and limited therapeutic options. Over the past 2 decades, however, the treatment paradigm has markedly shifted. SUMMARY: The introduction of tyrosine kinase inhibitors (TKIs), such as imatinib, dasatinib, and ponatinib, has revolutionized frontline therapy, significantly improving remission rates and long-term survival. These agents, when combined with reduced-intensity chemotherapy or even with corticosteroids, have enabled less toxic regimens, particularly beneficial for older or unfit patients. The implementation of measurable residual disease monitoring has emerged as a pivotal tool for risk stratification and therapeutic decision-making. Consequently, the role of allogeneic hematopoietic stem cell transplantation, considered a cornerstone of curative treatment, is being reevaluated in patients achieving sustained deep molecular responses. More recently, immunotherapeutic strategies - including the bispecific T-cell engager blinatumomab and chimeric antigen receptor (CAR) T-cell therapies - have emerged as effective alternatives to conventional chemotherapy and TKIs. KEY MESSAGES: While TKIs remain the backbone of treatment, the integration of immunotherapeutic strategies - including bispecific antibodies and CAR T-cell therapy - has expanded therapeutic options, not only in the R/R setting but increasingly in frontline regimens. Ongoing research aimed at optimizing the sequencing, combination, and duration of these therapies is essential to further enhance clinical outcomes.

论文信息

作者
Torrent A、Ribera JM
单位
ICO Badalona, Hospital Universitari Germans Trias i Pujol, Institut d'Investigació contra la Leucèmia Josep Carreras, Universitat Autònoma de Barcelona, Barcelona, Spain, atorrent@iconcologia.net.Spain
文献类型
综述
期刊
Acta haematologica2026
原文标识
PubMed 40555197 · DOI 10.1159/000547026