Recently, we defined "CML-like" subtype of BCR::ABL1-positive acute lymphoblastic leukemia (ALL), resembling lymphoid blast crisis of chronic myeloid leukemia (CML). Here we retrospectively analyzed prognostic relevance of minimal residual disease (MRD) and other features in 147 children with BCR::ABL1-positive ALL (diagnosed I/2000-IV/2021, treated according to EsPhALL (n = 133) or other (n = 14) protocols), using DNA-based monitoring of BCR::ABL1 genomic breakpoint and clonal immunoglobulin/T-cell receptor gene rearrangements. Although overall prognosis of CML-like (n = 48) and typical ALL (n = 99) was similar (5-year-EFS 60% and 49%, respectively; 5-year-OS 75% and 73%, respectively), typical ALL presented more relapses while CML-like patients more often died in the first remission. Prognostic role of MRD was significant in the typical ALL (p = 0.0005 in multivariate analysis for EFS). In contrast, in CML-like patients MRD was not significant (p values > 0.2) and inapplicable for therapy adjustment. Moreover, in the typical ALL, risk-prediction could be further improved by considering initial hyperleukocytosis. Early distinguishing typical BCR::ABL1-positive ALL and CML-like patients is essential to enable optimal treatment approach in upcoming protocols. For the typical ALL, tyrosine-kinase inhibitors and concurrent chemotherapy with risk-directed intensity should be recommended; in the CML-like disease, no relevant prognostic feature applicable for therapy tailoring was found so far.

Centre for Medical Genetics and Reproductive Medicine GENNET Prague Czech Republic

Charité Universitätsmedizin Berlin Berlin Germany

CLIP Prague Czech Republic

Department of Human Genetics University Hospital Heidelberg Heidelberg Germany

Department of Paediatric Haematology and Oncology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Pediatric Hematology and Oncology Medical School Hannover Hannover Germany

EsPhALL Trial Data Center School of Medicine and Surgery University of Milano Bicocca Monza Italy

Medical Genetics School of Medicine and Surgery University of Milano Bicocca Monza Italy

Pediatric Hemato Oncolgy Fondazione MBBM ASST Monza University of Milano Bicocca Monza Italy

Pediatrics University Hospital Schleswig Holstein Campus Kiel Kiel Germany

Tettamanti Research Center Pediatrics University of Milano Bicocca Fondazione Tettamanti Monza Italy

University Hospital Motol Prague Czech Republic

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