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Acute Lymphoblastic Leukemia
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
Ferrata Storti Foundation
Haematologica 2020 Volume 105(7):1887-1894
Gunnar Cario,1* Veronica Leoni,2* Valentino Conter,2* Andishe Attarbaschi,3 Marketa Zaliova,4 Lucie Sramkova,4 Gianni Cazzaniga,2 Grazia Fazio,2 Rosemary Sutton,5 Sarah Elitzur,6 Shai Izraeli,6 Melchior Lauten,7
Franco Locatelli,8 Giuseppe Basso,9 Barbara Buldini,9 Anke K. Bergmann,10 Jana Lentes,10 Doris Steinemann,10 Gudrun Göhring,10
Brigitte Schlegelberger,10 Oskar A. Haas,3 Denis Schewe,1
Swantje Buchmann,1 Anja Moericke,1 Deborah White,11 Tamas Revesz,12 Martin Stanulla,13 Georg Mann,3 Nicole Bodmer,14 Nira Arad-Cohen,15 Jan Zuna,4 Maria Grazia Valsecchi,2 Martin Zimmermann,13
Martin Schrappe1# and Andrea Biondi2#
1Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany; 2Clinica Pediatrica and Centro Ricerca Tettamanti, Università di Milano-Bicocca, Fondazione MBBM/ S.Gerardo Hospital, Monza, Italy; 3St. Anna Kinderspital and Children’s Cancer Research Institute, Vienna, Austria; 4CLIP, Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic; 5Molecular Diagnostics, Children’s Cancer Institute, University of NSW, Sydney, NSW, Australia; 6Pediatric Hematology-Oncology, Schneider Children's Medical Center, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Israel; 7Pediatrics, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany; 8Department of Pediatric Hematology and Oncology, Scientific Institute for Research and Healthcare (IRCCS) Childrens' Hospital Bambino Gesù, Sapienza, University of Rome, Rome, Italy; 9IIGM Torino and Pediatric Hemato-Oncology, SDB Departiment, University of Padova, Padova, Italy; 10Department of Human Genetics, Medical School Hannover, Hannover, Germany; 11Cancer Theme, South Australian Health and Medical Research Institute, Adelaide, Australia; 12Women’s and Children’s Hospital, SA Pathology, University of Adelaide, Adelaide, Australia; 13Department of Pediatric Hematology/Oncology, Hannover Medical School, Hannover, Germany; 14University Children’s Hospital Zurich, Zurich, Switzerland and 15Pediatric Hematology-Oncology Department, Ruth Rappaport Children’s Hospital, Rambam Health Care Campus, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
*GC, VL and VC contributed equally as co-first authors. #MS and AB contributed equally as co-senior authors.
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 posi- tive 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 treat- ment 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
Correspondence:
GUNNAR CARIO
gunnar.cario@uksh.de
Received: July 8, 2019. Accepted: October 10, 2019. Pre-published: October 10, 2019.
doi:10.3324/haematol.2019.231720
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