1. 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
- Author
-
Melchior Lauten, Georg Mann, Shai Izraeli, Jana Lentes, Martin Zimmermann, Martin Stanulla, Grazia Fazio, Barbara Buldini, Tamas Revesz, Rosemary Sutton, Marketa Zaliova, Andishe Attarbaschi, Anja Moericke, Nicole Bodmer, Sarah Elitzur, Maria Grazia Valsecchi, Brigitte Schlegelberger, Nira Arad-Cohen, Denis M. Schewe, Martin Schrappe, Gudrun Göhring, Gunnar Cario, Franco Locatelli, Oskar A. Haas, Valentino Conter, Lucie Sramkova, Veronica Leoni, Andrea Biondi, Giovanni Cazzaniga, Anke K. Bergmann, Jan Zuna, Deborah L. White, Giuseppe Basso, Swantje Buchmann, Doris Steinemann, Cario, G, Leoni, V, Conter, V, Attarbaschi, A, Zaliova, M, Sramkova, L, Cazzaniga, G, Fazio, G, Sutton, R, Elitzur, S, Izraeli, S, Lauten, M, Locatelli, F, Basso, G, Buldini, B, Bergmann, A, Lentes, J, Steinemann, D, Göhring, G, Schlegelberger, B, Haas, O, Schewe, D, Buchmann, S, Moericke, A, White, D, Revesz, T, Stanulla, M, Mann, G, Bodmer, N, Arad-Cohen, N, Zuna, J, Valsecchi, M, Zimmermann, M, Schrappe, M, and Biondi, A
- Subjects
Oncology ,medicine.medical_specialty ,ABL-class fusion ,medicine.drug_class ,medicine.medical_treatment ,Fusion Proteins, bcr-abl ,antineoplastic combined chemotherapy protocols ,B-lymphocytes ,child ,Hematopoietic stem cell transplantation ,Tyrosine-kinase inhibitor ,Recurrence ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Humans ,Cumulative incidence ,Pediatric Acute Lymphoblastic Leukemia ,Child ,Chemotherapy ,B-Lymphocytes ,ABL ,business.industry ,Hematology ,Articles ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Acute Lymphoblastic Leukemia ,Prognosis ,Tyrosin Kinase Inhibitors ,Minimal residual disease ,Transplantation ,Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,Stem cell ,business ,ALL - 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-Munster) 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).
- Published
- 2020