肿瘤细胞治疗研究
英文原题：Optimization of upfront therapy for adult acute lymphoblastic leukemia: a paradigm shift toward immunotherapy.
成人急性淋巴细胞白血病（ALL）的治疗方案正在演变，一线治疗现已纳入靶向免疫治疗药物。
成人急性淋巴细胞白血病（ALL）治疗方案持续演进，目前一线治疗已纳入靶向免疫治疗药物。靶向免疫疗法，如blinatumomab、inotuzumab ozogamicin（InO）、利妥昔单抗和nelarabine，正与传统化疗方案联合，以提高缓解率和微小残留病（MRD）阴性率，同时降低毒性。将blinatumomab纳入费城染色体阴性（Ph−）和阳性（Ph+）ALL患者的一线方案，可显著促进早期MRD清除。InO作为初始治疗的应用日益增加，尤其用于老年或身体状况不适合强化治疗的患者。CD20阳性B-ALL患者在化疗中加入利妥昔单抗可改善长期结局。在青少年和青年成人（AYA）患者的儿童方案为基础的T细胞ALL治疗中加入nelarabine，可降低中枢神经系统（CNS）复发风险。包括Ph+和Ph样ALL在内的高危亚型现已接受免疫治疗和分子靶向治疗。Ph+ ALL患者的一线标准方案包括多药化疗、酪氨酸激酶抑制剂（TKI）dasatinib或ponatinib，以及blinatumomab，以增强分子应答并尽量减少异基因造血干细胞移植（allo-HCT）的需求。对于伴激酶活化改变的Ph样ALL患者，JAK抑制剂联合ABL类TKI、化疗和免疫治疗是当前早期临床试验探索的方案。在诊断时检测MRD并开展基因组分析，改变了治疗模式，使所有患者都可采用个体化治愈策略。临床试验研究旨在确定高危及MRD阳性患者接受靶向治疗和CAR-T细胞疗法的最佳顺序，以延长生存、降低毒性并减少首次缓解期对allo-HCT的依赖。
Adult acute lymphoblastic leukemia (ALL) treatment protocols are evolving with frontline therapy now incorporates targeted immunotherapeutic agents. Targeted immune therapies like blinatumomab, inotuzumab ozogamicin (InO), rituximab, and nelarabine are being combined with traditional chemotherapy protocols to enhance remission rates and minimal residual disease (MRD) negativity while decreasing toxicities. The incorporation of blinatumomab into initial treatment protocols for both Philadelphia chromosome-negative (Ph -) and positive (Ph +) ALL patients results in notable early MRD elimination. The medical use of InO as an initial treatment has increased specifically for older or medically unfit patients. The addition of rituximab to chemotherapy treatment in CD20-positive B-ALL patients produces superior long-term results. Adding nelarabine to pediatric-inspired T-cell ALL treatment protocols in young adult and adolescent (AYA) patients resulted in decrease their risk of central nervous system (CNS) relapse. High-risk ALL subtypes including Ph + and Ph-like ALL now receive immunotherapeutic and molecularly targeted treatments. Ph + ALL patients receive standard treatment with multi-agent chemotherapy and TKIs dasatinib or ponatinib and blinatumomab as part of their frontline therapy to enhance molecular responses and minimize the requirement for allogeneic hematopoietic stem cell transplantation (allo-HCT). The combination of JAK inhibitors with ABL-class TKIs, chemotherapy, and immunotherapy represents current early-phase trial approaches for Ph-like ALL patients with kinase-activating alterations. The practice of testing MRD and genomic profiling at diagnosis revolutionized treatment approaches by allowing personalized curative strategies for all patients. Research on clinical trials aims to establish the best sequence of targeted therapies and CAR T-cell therapy for high-risk and MRD-positive patients to achieve longer survival rates with reduced toxicity and less dependence on allo-HCT in first remission.
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