Optimizing treatment of acute myeloid leukemia in patients with Down syndrome: a new clinical protocol

Introduction. In Russia, there is currently no standard treatment for acute myeloid leukemia (AML) in children with Down syndrome (DS). The overall survival rates of patients with AML/myelodysplastic syndrome (MDS) and DS in Russia do not exceed 67%. The main problems encountered by these patients are high toxicity and severe infectious complications. Aim: to conduct a retrospective analysis of treatment outcomes in children with AML/MDS and DS in Russia treated according to different protocols, including those who received non-protocol treatment, and to develop of a uniform treatment protocol with reduced toxicity. Materials and methods. The analysis included 79 patients, 65 of them with AML and 14 with MDS, who received therapy at 40 Russian clinics from 2018 to 2024. Patient recruitment started in 2018 for the multicenter AML-MRD-2018 protocol study. Results. Seventy-six patients received specific therapy. A total of 50 (63%) patients underwent treatment according to the ML-DS-2006. Eleven patients (14%) were treated according to the AML-BFM-1998/2004 protocol and 15 (19%) patients received non-protocol treatment according to schemes “7 + 3”, “5 + 2”, low doses of cytarabine. Fifty-eight (75%) patients achieved complete remission. Initially refractory disease was reported in 3 patients (4%), relapses occurred in 6 (8%) patients. One child developed AML six months after the resolution of MDS. The median follow-up was 2 years and 4 months. The overall and event-free survival at 3 years in the patients with AML/MDS and DS were 66% (95% confidence interval 56–79) and 62% (95% confidence interval 52–75), respectively. Mortality among the patients reached 30%; 16 deaths (70%) occurred before remission, 12 (75%) of which were due to infectious complications. Conclusion. The AML-DS-2025 protocol with a reduced cumulative dose of anthracyclines but an increased total dose of cytarabine, in our opinion, should lead to improved long-term overall and event-free survival rates in children with AML/MDS and DS, as well as to decreased immediate and long-term toxicity.