Down syndrome ALL linked to poorer survival and greater toxicity in ALL-B12

Children with Down syndrome–associated acute lymphoblastic leukemia (DS-ALL) continue to have poorer outcomes than those without Down syndrome. Researchers assessed prognosis, relapse patterns, and treatment-related toxicities in the Japan Children's Cancer Group ALL-B12 trial, a nationwide prospective study using risk-adapted therapy. The analysis included 1,804 patients, of whom 44 had DS-ALL.

Five-year event-free survival was 70.5% in DS-ALL versus 85.6% in non-DS-ALL; overall survival was 81.8% versus 94.6% (P < 0.001). Differences were most pronounced among standard-risk patients. DS-ALL relapses were predominantly isolated bone marrow events, with no central nervous system relapse. Mucositis (27.3% versus 7.1%), hyperglycemia (25.0% versus 6.9%), and pulmonary infections (20.5% versus 7.4%) were more frequent in DS-ALL.

CRLF2 rearrangement was detected in 15 of 43 assessable DS-ALL cases. An exploratory analysis excluding canonical favorable or unfavorable subtypes found numerically lower survival with CRLF2 rearrangement, but differences were not statistically significant. All three DS-ALL patients with TP2 measurable residual disease ≥10⁻⁴ relapsed and died within three years. No treatment-related deaths were recorded after induction, although one death had an undetermined cause.

These findings support efforts to reduce both relapse and toxicity in DS-ALL. The small DS-ALL cohort, particularly the molecular and residual-disease subgroups, limits interpretation; the abstract does not establish which treatment modifications would improve outcomes.