Elitzur Sarah, Izraeli Shai
The Rina Zaizov Division of Pediatric Hematology-Oncology, Schneider Children's Medical Center, Petah Tikva, Israel, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Harefuah. 2023 Jan;162(1):57-63.
Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, constituting approximately 25% of childhood cancers. In recent decades, survival rates have improved dramatically, from approximately 10% in the 1960's to over 90% today. This tremendous achievement has been accomplished through collaborative randomized clinical trials, with progressive evolution of highly efficient, risk-adapted multi-agent chemotherapeutic regimens, effective central nervous system prophylactic strategies and improved supportive care. Recently, our understanding of the genetic basis of ALL has been greatly enhanced, and precise methods for treatment response assessment with serial measurements of minimal residual disease have been developed. Certain patient subgroups have genetically targetable lesions, such as Philadelphia-positive ALL, whose outcomes have been dramatically improved by combined tyrosine kinase inhibitors and chemotherapy, or specific patient subsets of "Philadelphia-like" ALL. Despite the great progress in curing childhood ALL, significant challenges still remain. Acute adverse effects of chemotherapy may be life-threatening, and long-term side effects often impair survivors' quality of life. Survival rates in patients with relapsed or refractory ALL remain poor. This led to the introduction of novel immune-based therapies into the treatment of relapsed/refractory B-ALL: blinatumomab, a CD19 bi-specific T-cell engager; inotuzumab- a CD22-immunotoxin, and CD19-CAR (chimeric antigen receptor) T cells. These modalities have demonstrated improved remission rates with reduced toxicity compared to chemotherapy. The role of immunotherapy in the treatment of newly-diagnosed and relapsed patients will be more precisely defined in the near future.
急性淋巴细胞白血病(ALL)是儿童期最常见的恶性肿瘤,约占儿童癌症的25%。近几十年来,生存率有了显著提高,从20世纪60年代的约10%提高到如今的90%以上。这一巨大成就得益于协作性随机临床试验,以及高效、风险适应性多药化疗方案的逐步演进、有效的中枢神经系统预防策略和改善的支持治疗。最近,我们对ALL遗传基础的理解有了极大增强,并且已经开发出通过连续测量微小残留病进行治疗反应评估的精确方法。某些患者亚组存在可进行基因靶向治疗的病变,如费城染色体阳性ALL,联合酪氨酸激酶抑制剂和化疗使其预后得到显著改善,或“费城样”ALL的特定患者亚组。尽管在治愈儿童ALL方面取得了巨大进展,但重大挑战依然存在。化疗的急性不良反应可能危及生命,长期副作用常常损害幸存者的生活质量。复发或难治性ALL患者的生存率仍然很低。这促使新型免疫疗法被引入复发/难治性B-ALL的治疗中:blinatumomab,一种CD19双特异性T细胞衔接器;inotuzumab,一种CD22免疫毒素,以及CD19嵌合抗原受体(CAR)T细胞。与化疗相比,这些疗法已显示出缓解率提高且毒性降低。免疫疗法在新诊断和复发患者治疗中的作用将在不久的将来得到更精确的界定。