Pediatrics · Hematology · 4 h ago
Blood BRAF V600E Burden Linked to Outcomes in Pediatric LCH
A five-center European study assessed peripheral blood BRAF V600E in 226 children with Langerhans cell histiocytosis (LCH). Higher mutation burden at diagnosis and failure to achieve a low burden after six weeks of vinblastine/prednisone were associated with inferior two-year event-free survival.
- Five centers analyzed blood samples from 226 children with LCH.
- Higher baseline BRAF V600E burden was associated with inferior two-year EFS.
- Lower burden after six weeks of treatment was associated with higher EFS.
- Prospective trials are needed to assess testing-guided risk stratification.
Researchers at five centers in the European Consortium for Histiocytosis analyzed peripheral blood from 226 children enrolled in, or managed according to, the LCH-IV protocol. They measured BRAF V600E burden in circulating cell-free DNA and peripheral blood mononuclear cell DNA at diagnosis and after six weeks of vinblastine/prednisone, then examined associations with two-year event-free survival (EFS).
At diagnosis, either DNA source detected BRAF V600E in children with multisystem LCH; testing both improved diagnostic sensitivity in single-system disease. Mutation-burden thresholds associated with inferior EFS varied by subgroup: at least the limit of quantification in single-system and multisystem risk-organ-negative disease, and at least 1% in multisystem risk-organ-positive disease. In multivariable analysis, burdens at or above these thresholds were associated with inferior EFS (hazard ratios 2.05 and 4.53, respectively). After six weeks of treatment, a falling burden below 0.1% in cell-free DNA or 0.01% in mononuclear cell DNA was associated with higher EFS.
The findings support evaluating blood BRAF V600E measurement for risk stratification in prospective international trials. The study reports associations; it does not establish that testing-guided treatment changes improve outcomes.
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Blood Advances: A European study on blood mutation monitoring in children with BRAFV600E-positive Langerhans Cell Histiocytosis ↗This is an automated AI-condensed summary that has not yet been reviewed by an editor. Always consult the full item at the original source.