肿瘤细胞治疗研究
英文原题：Incorporating Immunotherapies into the Evolving Standard of Care for Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia.
在高收入国家，由于风险适应性化疗和可测量残留病（MRD）指导策略，儿童B细胞前体急性淋巴细胞白血病（BCP-ALL）的生存率超过90%。
在高收入国家，由于风险适应性化疗和可测量残留病（MRD）指导策略，儿童B细胞前体急性淋巴细胞白血病（BCP-ALL）的生存率超过90%。然而，复发仍是主要死亡原因，化疗相关毒性凸显了对同等有效、毒性更低方法的需求。靶向CD19和CD22的B细胞导向免疫疗法已成为变革性模式。本综述综合了三类主要免疫疗法的临床证据：CD19/CD3 T细胞衔接器（blinatumomab）、CD22抗体药物偶联物（inotuzumab ozogamicin（InO））和靶向CD19的嵌合抗原受体（CAR）-T细胞疗法，评估其整合至一线和复发治疗算法、安全性、耐药机制及未来方向。随机儿童试验表明，blinatumomab纳入一线和首次复发治疗时，主要通过巩固治疗，通过减少复发和治疗相关死亡率提高生存率。InO在复发疾病中显示出高诱导缓解率和MRD阴性率，但携带肝窦阻塞综合征风险，尤其在造血干细胞移植（HSCT）前后。CD19 CAR-T细胞疗法在80-90%的重度预处理患者中诱导MRD阴性缓解，40-50%的患者无需强制HSCT巩固即可获得持久生存。新兴药物和联合策略旨在克服抗原逃逸并提高持久性。中枢神经系统（CNS）疾病控制、长期免疫效应、测序、监管差异和全球可及性方面仍存在挑战。免疫疗法正在重塑儿童BCP-ALL的治疗格局，使得在维持或提高治愈率的同时减少化疗成为可能。战略性整合与全球公平可及对于实现低毒性的普遍治愈至关重要。免疫治疗后的复发可能表现出独特的疾病特征，需要新的治疗方法。
Survival for pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) exceeds 90% in high-income countries due to risk-adapted chemotherapy and measurable residual disease (MRD)-guided strategies. However, relapse remains a leading cause of death, and chemotherapy-related toxicities highlight the need for equally effective, less toxic approaches. B-cell-directed immunotherapies targeting CD19 and CD22 have emerged as transformative modalities. This review synthesizes clinical evidence for three major immunotherapeutic classes: CD19/CD3 T cell engagers (blinatumomab), CD22 antibody-drug conjugates (inotuzumab ozogamicin (InO)), and CD19-directed chimeric antigen receptor (CAR)-T cell therapies, evaluating their integration into frontline and relapsed treatment algorithms, safety, resistance mechanisms, and future directions. Randomized pediatric trials demonstrate that blinatumomab improves survival by reducing relapse and treatment-related mortality when incorporated into frontline and first-relapse therapy, primarily in consolidation. InO shows high induction response and MRD-negativity rates in relapsed disease but carries a risk of sinusoidal obstruction syndrome, particularly around hematopoietic stem cell transplantation (HSCT). CD19 CAR-T cell therapy induces MRD-negative remissions in 80-90% of heavily pretreated patients, with durable survival in 40-50% without mandatory HSCT consolidation. Emerging agents and combination strategies aim to overcome antigen escape and improve durability. Challenges remain regarding central nervous system (CNS) disease control, long-term immune effects, sequencing, regulatory disparities, and global access. Immunotherapies are reshaping pediatric BCP-ALL treatment, enabling chemotherapy reduction while maintaining or improving cure rates. Strategic integration and equitable global access are vital to achieving universal cures with reduced toxicity. Post-immunotherapy relapses may exhibit distinct disease characteristics requiring novel treatment approaches.
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