A risk score including microdeletions improves relapse prediction for standard and medium risk precursor B-cell acute lymphoblastic leukaemia in children
Аннотация:Summary To prevent relapse, high risk paediatric acute lymphoblastic leukaemia ( ALL ) is treated very intensively. However, most patients who eventually relapse have standard or medium risk ALL with low minimal residual disease ( MRD ) levels. We analysed recurrent microdeletions and other clinical prognostic factors in a cohort of 475 uniformly treated non‐high risk precursor B‐cell ALL patients with the aim of better predicting relapse and refining risk stratification. Lower relapse‐free survival at 7 years ( RFS ) was associated with IKZF 1 intragenic deletions ( P < 0·0001); P2 RY 8 ‐ CRLF 2 gene fusion ( P < 0·0004); Day 33 MRD >5 × 10 −5 ( P < 0·0001) and High National Cancer Institute ( NCI ) risk ( P < 0·0001). We created a predictive model based on a risk score ( RS ) for deletions, MRD and NCI risk, extending from an RS of 0 ( RS 0) for patients with no unfavourable factors to RS 2 + for patients with 2 or 3 high risk factors. RS 0, RS 1, and RS 2 + groups had RFS of 93%, 78% and 49%, respectively, and overall survival ( OS ) of 99%, 91% and 71%. The RS provided greater discrimination than MRD ‐based risk stratification into standard (89% RFS , 96% OS ) and medium risk groups (79% RFS , 91% OS ). We conclude that this RS may enable better early therapeutic stratification and thus improve cure rates for childhood ALL .
