Minimal residual disease in BCR::ABL1-positive acute lymphoblastic leukemia: different significance in typical ALL and in CML-like disease

Autor: Jan Zuna, Lenka Hovorkova, Justina Krotka, Amelie Koehrmann, Michela Bardini, Lucie Winkowska, Eva Fronkova, Julia Alten, Rolf Koehler, Cornelia Eckert, Lisa Brizzolara, Marie Trkova, Jan Stuchly, Martin Zimmermann, Paola De Lorenzo, Maria Grazia Valsecchi, Valentino Conter, Jan Stary, Martin Schrappe, Andrea Biondi, Jan Trka, Marketa Zaliova, Giovanni Cazzaniga, Gunnar Cario
Přispěvatelé: Zuna, J, Hovorkova, L, Krotka, J, Koehrmann, A, Bardini, M, Winkowska, L, Fronkova, E, Alten, J, Koehler, R, Eckert, C, Brizzolara, L, Trkova, M, Stuchly, J, Zimmermann, M, De Lorenzo, P, Valsecchi, M, Conter, V, Stary, J, Schrappe, M, Biondi, A, Trka, J, Zaliova, M, Cazzaniga, G, Cario, G
Rok vydání: 2022
Předmět:
Zdroj: Leukemia. 36:2793-2801
ISSN: 1476-5551
0887-6924
DOI: 10.1038/s41375-022-01668-0
Popis: 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.
Databáze: OpenAIRE
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