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

Gunnar Cario, Veronica Leoni, Valentino Conter, Andishe Attarbaschi, Marketa Zaliova, Lucie Sramkova, Gianni Cazzaniga, Grazia Fazio, Rosemary Sutton, Sarah Elitzur, Shai Izraeli, Melchior Lauten, Franco Locatelli, Giuseppe Basso, Barbara Buldini, Anke K. Bergmann, Jana Lentes, Doris Steinemann, Gudrun Göhring, Brigitte SchlegelbergerOskar A. Haas, Denis Schewe, Swantje Buchmann, Anja Moericke, Deborah White, Tamas Revesz, Martin Stanulla, Georg Mann, Nicole Bodmer, Nira Arad-Cohen, Jan Zuna, Maria Grazia Valsecchi, Martin Zimmermann, Martin Schrappe, Andrea Biondi

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31 Citations (Scopus)

Abstract

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 ≥5x10-4 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).

Original languageEnglish
Pages (from-to)1887-1894
Number of pages8
JournalHaematologica
Volume105
Issue number7
DOIs
Publication statusPublished or Issued - 1 Jul 2020

ASJC Scopus subject areas

  • Hematology

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