Pediatric Oncology and Hematology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Erlangen, Germany.
Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen, Germany.
Leukemia. 2023 Mar;37(3):505-517. doi: 10.1038/s41375-023-01822-2. Epub 2023 Jan 27.
Treatment of chronic myeloid leukemia has improved significantly with the introduction of tyrosine kinase inhibitors (TKIs), and treatment guidelines based on numerous clinical trials are available for chronic phase disease. However for CML in the blast phase (CML-BP), prognosis remains poor and treatment options are much more limited. The spectrum of treatment strategies for children and adolescents with CML-BP has largely evolved empirically and includes treatment principles derived from adult CML-BP and pediatric acute leukemia. Given this heterogeneity of treatment approaches, we formed an international panel of pediatric CML experts to develop recommendations for consistent therapy in children and adolescents with this high-risk disease based on the current literature and national standards. Recommendations include detailed information on initial diagnosis and treatment monitoring, differentiation from Philadelphia-positive acute leukemia, subtype-specific selection of induction therapy, and combination with tyrosine kinase inhibitors. Given that allogeneic hematopoietic stem cell transplantation currently remains the primary curative intervention for CML-BP, we also provide recommendations for the timing of transplantation, donor and graft selection, selection of a conditioning regimen and prophylaxis for graft-versus-host disease, post-transplant TKI therapy, and management of molecular relapse. Management according to the treatment recommendations presented here is intended to provide the basis for the design of future prospective clinical trials to improve outcomes for this challenging disease.
随着酪氨酸激酶抑制剂(TKI)的引入,慢性髓性白血病的治疗有了显著改善,针对慢性期疾病的治疗指南也已基于大量临床试验制定。然而,对于急变期慢性髓性白血病(CML-BP),预后仍然较差,治疗选择也更为有限。儿童和青少年 CML-BP 的治疗策略范围主要是经验性发展的,包括源自成人 CML-BP 和儿童急性白血病的治疗原则。鉴于这种治疗方法的异质性,我们组建了一个国际儿科 CML 专家小组,根据当前文献和国家标准,为这种高危疾病的儿童和青少年制定一致治疗的建议。建议包括有关初始诊断和治疗监测、与费城阳性急性白血病的鉴别、诱导治疗的亚型特异性选择以及与酪氨酸激酶抑制剂联合使用的详细信息。鉴于异基因造血干细胞移植目前仍然是 CML-BP 的主要治疗干预措施,我们还为移植的时机、供体和移植物的选择、预处理方案的选择以及移植物抗宿主病的预防、移植后 TKI 治疗以及分子复发的管理提供了建议。根据这里提出的治疗建议进行管理,旨在为未来改善这种具有挑战性的疾病的预后的前瞻性临床试验设计提供基础。