aDepartment of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children's Hospital, Rome bUniversity of Pavia, Pavia, Italy.
Curr Opin Oncol. 2013 Nov;25(6):707-15. doi: 10.1097/CCO.0000000000000011.
To review and summarize the available evidence on factors predicting prognosis of children with relapsed acute lymphoblastic leukemia (ALL) and on the currently used treatment strategies, as well as on the most promising and innovative molecular or cellular therapies.
Relapse still represents the most common cause of treatment failure, occurring in approximately 15-20% of childhood ALL. Risk-oriented standard salvage regimens are mostly based on combinations of the same agents incorporated in frontline therapies. Allogeneic hematopoietic stem cell transplantation (HSCT) is largely employed as postremission therapy, being superior to chemotherapy in high-risk patients. With conventional therapies including HSCT, 40-50% of children with relapsed ALL can be rescued. Thus, innovative approaches are needed to further improve the outcome of patients, especially when carrying poor prognostic factors. The last decade has witnessed the development of novel agents, including nucleoside analogues, anti-CD22 monoclonal antibodies and bi-specific, anti-CD3/CD19 antibodies, together with new formulations of existing chemotherapeutic agents and targeted molecules, such as tyrosine kinase inhibitors and FLT3 inhibitors.
A significant proportion of children with relapsed ALL are salvaged by risk-oriented therapies. Novel agents should be integrated into combination regimens with the aim of further improving outcome of patients.
回顾和总结预测儿童复发急性淋巴细胞白血病（ALL）预后的因素和目前使用的治疗策略的现有证据，以及最有前途和创新的分子或细胞疗法。
复发仍然是治疗失败的最常见原因，约发生在 15-20%的儿童 ALL 中。风险导向的标准挽救方案主要基于一线治疗中包含的相同药物的组合。异基因造血干细胞移植（HSCT）主要用作缓解后治疗，在高危患者中优于化疗。通过包括 HSCT 在内的常规治疗，40-50%的复发 ALL 患儿可以得到挽救。因此，需要创新方法来进一步改善患者的预后，特别是在存在不良预后因素的情况下。过去十年见证了新型药物的发展，包括核苷类似物、抗 CD22 单克隆抗体和双特异性、抗 CD3/CD19 抗体，以及现有化疗药物和靶向分子的新制剂，如酪氨酸激酶抑制剂和 FLT3 抑制剂。
通过风险导向治疗，相当一部分复发 ALL 患儿得到挽救。应将新型药物纳入联合治疗方案，以进一步提高患者的预后。
