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


Journal

Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895

Informations de publication

Date de publication:
12 2022
Historique:
received: 14 04 2022
accepted: 22 07 2022
revised: 21 07 2022
pubmed: 7 8 2022
medline: 3 12 2022
entrez: 6 8 2022
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 35933523
doi: 10.1038/s41375-022-01668-0
pii: 10.1038/s41375-022-01668-0
doi:

Substances chimiques

Fusion Proteins, bcr-abl EC 2.7.10.2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2793-2801

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer Nature Limited.

Références

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Auteurs

Jan Zuna (J)

CLIP (Childhood Leukaemia Investigation Prague), Prague, Czech Republic. jan.zuna@lfmotol.cuni.cz.
Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic. jan.zuna@lfmotol.cuni.cz.
University Hospital Motol, Prague, Czech Republic. jan.zuna@lfmotol.cuni.cz.

Lenka Hovorkova (L)

CLIP (Childhood Leukaemia Investigation Prague), Prague, Czech Republic.
Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.

Justina Krotka (J)

CLIP (Childhood Leukaemia Investigation Prague), Prague, Czech Republic.
Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
University Hospital Motol, Prague, Czech Republic.

Amelie Koehrmann (A)

Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.

Michela Bardini (M)

Tettamanti Research Center, Pediatrics, University of Milano-Bicocca/Fondazione Tettamanti, Monza, Italy.

Lucie Winkowska (L)

CLIP (Childhood Leukaemia Investigation Prague), Prague, Czech Republic.
Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.

Eva Fronkova (E)

CLIP (Childhood Leukaemia Investigation Prague), Prague, Czech Republic.
Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
University Hospital Motol, Prague, Czech Republic.

Julia Alten (J)

Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.

Rolf Koehler (R)

Department of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany.

Cornelia Eckert (C)

Charité-Universitätsmedizin Berlin, Berlin, Germany.

Lisa Brizzolara (L)

Tettamanti Research Center, Pediatrics, University of Milano-Bicocca/Fondazione Tettamanti, Monza, Italy.

Marie Trkova (M)

Centre for Medical Genetics and Reproductive Medicine GENNET, Prague, Czech Republic.

Jan Stuchly (J)

CLIP (Childhood Leukaemia Investigation Prague), Prague, Czech Republic.
Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.

Martin Zimmermann (M)

Department of Pediatric Hematology and Oncology, Medical School Hannover, Hannover, Germany.

Paola De Lorenzo (P)

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

Maria Grazia Valsecchi (MG)

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

Valentino Conter (V)

Pediatric Hemato-Oncolgy, Fondazione MBBM/ASST-Monza, University of Milano-Bicocca, Monza, Italy.

Jan Stary (J)

Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
University Hospital Motol, Prague, Czech Republic.

Martin Schrappe (M)

Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.

Andrea Biondi (A)

Pediatric Hemato-Oncolgy, Fondazione MBBM/ASST-Monza, University of Milano-Bicocca, Monza, Italy.

Jan Trka (J)

CLIP (Childhood Leukaemia Investigation Prague), Prague, Czech Republic.
Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
University Hospital Motol, Prague, Czech Republic.

Marketa Zaliova (M)

CLIP (Childhood Leukaemia Investigation Prague), Prague, Czech Republic.
Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
University Hospital Motol, Prague, Czech Republic.

Giovanni Cazzaniga (G)

Tettamanti Research Center, Pediatrics, University of Milano-Bicocca/Fondazione Tettamanti, Monza, Italy.
Medical Genetics, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.

Gunnar Cario (G)

Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.

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Classifications MeSH