Acute lymphoblastic leukemia in children with Down syndrome: “Moscow–Berlin” experience

Abstract

Down syndrome (DS) is one of the most common chromosomal abnormalities. Children with DS are more likely to develop acute lymphoblastic leukemia (ALL). Standard therapy is usually used to treat DS-ALL, but children with DS-ALL have an inferior outcome compared to non-DS patients, mainly due to increased therapy toxicity. The purpose of the study: in this study we aimed to analyze our experience of treating DS-ALL according to original protocol “Moscow–Berlin”. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The analysis included primary ALL patients, aged 1 to 18 years, who received therapy in Russian and Belarusian clinics participating in the “Moscow–Berlin” study from January 2008 to December 2020. To analyze the treatment results of SD-ALL patients, a comparison group was formed from all patients with ALL registered in the database, using the matched-pair method. A total of 8296 ALL patients were registered in the database, of which 135 (1.63%) were patients with DS-ALL. The predominant age group of DS-ALL patients is 3–10 years. Among them there was no T-cell ALL patient, and both favorable and unfavorable genetic abnormalities were significantly less common. There were no differences in early response between DS-ALL and non-DS-ALL patients. The event-free (61 ± 6%) and overall survival (74 ± 4%) of DS-ALL patients was significantly lower than in the comparison group (84 ± 3% and 89 ± 3% respectively; p < 0.001). No differences were found in relapse rate, while the treatment-related mortality (TRM) was higher in DS-ALL group (19.3 ± 3.5% versus 3.9 ± 1.2%; p˂0.001) in all treatment phase. The treatment results for DS-ALL patients remain unsatisfactory; therefore, new approaches to optimizing therapy are needed. High toxicity and associated TRM are the main problem. Future strategies to improve outcome in DS-ALL should include improved supportive care, the use of targeted drugs and immunotherapy, as well as the identification of new molecular genetic features.