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A risk score including microdeletions improves relapse prediction for standard and medium risk precursor B‐cell acute lymphoblastic leukaemia in children
Author(s) -
Sutton Rosemary,
Venn Nicola C.,
Law Tamara,
Boer Judith M.,
Trahair Toby N.,
Ng Anthea,
Den Boer Monique L.,
Dissanayake Anuruddhika,
Giles Jodie E.,
Dalzell Pauline,
Mayoh Chelsea,
Barbaric Draga,
Revesz Tamas,
Alvaro Frank,
Pieters Rob,
Haber Michelle,
Norris Murray D.,
Schrappe Martin,
Dalla Pozza Luciano,
Marshall Glenn M
Publication year - 2018
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.15056
Subject(s) - medicine , risk stratification , minimal residual disease , oncology , cohort , framingham risk score , risk model , disease , leukemia , risk analysis (engineering)
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 .