The authors of what is believed to be the first multinational study to compare MRD and long-term clinical outcomes in patients with acute lymphocytic leukemia (ALL) with or without Down syndrome conclude that customized strategies and novel approaches are needed in the treatment of patients who have both ALL and Down syndrome. The study was published in Lancet Haematology in October.
The matched cohort study compared children and adolescents aged 1 to 23 years with Down syndrome and ALL with matched controls who did not have Down syndrome. All patients were treated between 2002 and 2018 in one of seven MRD-guided trials conducted in the Netherlands, Australia, Germany, and seven Nordic and Baltic countries. The primary endpoint was MRD levels in the two groups of patients. The secondary endpoint was long-term outcomes (event-free survival, overall survival, relapse, and treatment-related mortality [TRM]).
Similar numbers of patients in both groups had high MRD at the end of induction treatment. However, among patients in both groups with the IKZF1 deletion, patients with Down syndrome had a higher risk of both relapse (37.1% risk at 5 years compared with 13.2% for matched controls) and TRM (12.2% at 5 years compared with 2.7% for matched controls).
“Down syndrome itself provides an additional risk in individuals with IKZF1 deletions, suggesting an interplay between the germline environment and this poor risk somatic aberration,” write senior author Professor C. Michel Zwaan, of the Princess Máxima Center for Pediatric Oncology in the Netherlands, and his colleagues. “Different treatment strategies are warranted considering both inherent risk of relapse and high risk of TRM.”
- Michels N, Boer JM, Enshaei A, et al. Minimal residual disease, long-term outcome, and IKZF1 deletions in children and adolescents with Down syndrome and acute lymphocytic leukaemia: a matched cohort study. Lancet Haematol. 2021;8(10):e700-e710. doi:10.1016/S2352-3026(21)00272-6