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Relapses and treatment-related events contributed equally to poor prognosis in children with ABL-class fusion positive B-cell acute lymphoblastic leukemia treated according to AIEOP-BFM protocols

G. Cario, V. Leoni, V. Conter, A. Attarbaschi, M. Zaliova, L. Sramkova, G. Cazzaniga, G. Fazio, R. Sutton, S. Elitzur, S. Izraeli, M. Lauten, F. Locatelli, G. Basso, B. Buldini, AK. Bergmann, J. Lentes, D. Steinemann, G. Göhring, B....

. 2020 ; 105 (7) : 1887-1894. [pub] 20191010

Language English Country Italy

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

Persistent link   https://www.medvik.cz/link/bmc21020393

Grant support
NV15-30626A MZ0 CEP Register

ABL-class fusions other than BCR-ABL1 characterize around 2-3% of precursor B-cell acute lymphoblastic leukemia. Case series indicated that patients suffering from these subtypes have a dismal outcome and may benefit from the introduction of tyrosine kinase inhibitors. We analyzed clinical characteristics and outcome of 46 ABL-class fusion positive cases other than BCR-ABL1 treated according to AIEOP-BFM (Associazione Italiana di Ematologia-Oncologia Pediatrica-Berlin-Frankfurt-Münster) ALL 2000 and 2009 protocols; 13 of them received a tyrosine kinase inhibitor (TKI) during different phases of treatment. ABL-class fusion positive cases had a poor early treatment response: minimal residual disease levels of ≥5×10-4 were observed in 71.4% of patients after induction treatment and in 51.2% after consolidation phase. For the entire cohort of 46 cases, the 5-year probability of event-free survival was 49.1+8.9% and that of overall survival 69.6+7.8%; the cumulative incidence of relapse was 25.6+8.2% and treatment-related mortality (TRM) 20.8+6.8%. One out of 13 cases with TKI added to chemotherapy relapsed while eight of 33 cases without TKI treatment suffered from relapse, including six in 17 patients who had not received hematopoietic stem cell transplantation. Stem cell transplantation seems to be effective in preventing relapses (only three relapses in 25 patients), but was associated with a very high TRM (6 patients). These data indicate a major need for an early identification of ABL-class fusion positive acute lymphoblastic leukemia cases and to establish a properly designed, controlled study aimed at investigating the use of TKI, the appropriate chemotherapy backbone and the role of hematopoietic stem cell transplantation. (Registered at: clinicaltrials.gov identifier: NTC00430118, NCT00613457, NCT01117441).

Cancer Theme South Australian Health and Medical Research Institute Adelaide Australia

Clinica Pediatrica and Centro Ricerca Tettamanti Università di Milano Bicocca Fondazione MBBM S Gerardo Hospital Monza Italy

CLIP Department of Pediatric Hematology and Oncology 2Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic

Department of Human Genetics Medical School Hannover Hannover Germany

Department of Pediatric Hematology and Oncology Scientific Institute for Research and Healthcare Childrens' Hospital Bambino Gesù Sapienza University of Rome Rome Italy

Department of Pediatric Hematology Oncology Hannover Medical School Hannover Germany

IIGM Torino and Pediatric Hemato Oncology SDB Departiment University of Padova Padova Italy

Molecular Diagnostics Children's Cancer Institute University of NSW Sydney NSW Australia

Pediatric Hematology Oncology Department Ruth Rappaport Children's Hospital Rambam Health Care Campus Rappaport Faculty of Medicine Technion Israel Institute of Technology Haifa Israel

Pediatric Hematology Oncology Schneider Children's Medical Center Petah Tikva and Sackler Faculty of Medicine Tel Aviv University Israel

Pediatrics University Hospital Schleswig Holstein Campus Kiel Kiel Germany

Pediatrics University Hospital Schleswig Holstein Campus Lübeck Lübeck Germany

St Anna Kinderspital and Children's Cancer Research Institute Vienna Austria

University Children's Hospital Zurich Zurich Switzerland

Women's and Children's Hospital SA Pathology University of Adelaide Adelaide Australia

References provided by Crossref.org

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