Abstract
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.
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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
This study was supported by grants from the Czech Health Research Council (NU21-03-00128) and Charles University (UNCE 204012), by the project (Ministry of Health, Czech Republic) for conceptual development of research organization 00064203 (University Hospital Motol, Prague, Czech Republic), by the project National Institute for Cancer Research (Program EXCELES, ID Project No. LX22NPO5102)—Funded by the European Union—Next Generation EU, by Deutsche Krebshilfe (70112958), by the Italian Association for Cancer Research (AIRC) to AB (IG2017—20564) and G. Cazzaniga (IG2015—17593), and by the Comitato Maria Letizia Verga.
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JZ, G.Cario, GCazzaniga, and MZ designed the study; LH, JK, AK, MB, LW, EF, JA, RK, CE, LB, MT, and JStu analyzed samples and provided data; MZ, PDL, MGV, VC, JSta, MS, AB, and JT provided diagnostic and clinical data; all authors participated on data integration, interpretation, and presentation; JZ and MZ wrote the draft; and all authors revised the draft and contributed to the final paper.
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Zuna, J., Hovorkova, L., Krotka, J. et al. Minimal residual disease in BCR::ABL1-positive acute lymphoblastic leukemia: different significance in typical ALL and in CML-like disease. Leukemia 36, 2793–2801 (2022). https://doi.org/10.1038/s41375-022-01668-0
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DOI: https://doi.org/10.1038/s41375-022-01668-0