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Outcome of ABL-class acute lymphoblastic leukemia in children in the pre-tyrosine kinase inhibitor era; an international retrospective study of the Ponte di Legno group
- Source :
- Lancet Haematol
- Publication Year :
- 2020
-
Abstract
- Background: ABL-class fusion genes other than BCR–ABL1 have been identified in approximately 3% of children with newly diagnosed acute lymphocytic leukaemia, and studies suggest that leukaemic cells carrying ABL-class fusions can be targeted successfully by tyrosine-kinase inhibitors. We aimed to establish the baseline characteristics and outcomes of paediatric patients with ABL-class fusion B-cell acute lymphocytic leukaemia in the pre-tyrosine-kinase inhibitor era. Methods: This multicentre, retrospective, cohort study included paediatric patients (aged 1–18 years) with newly diagnosed ABL-class fusion (ABL1 fusion-positive, ABL2 fusion-positive, CSF1R fusion-positive, and PDGFRB fusion-positive) B-cell acute lymphocytic leukaemia enrolled in clinical trials of multidrug chemotherapy done between Oct 3, 2000, and Aug 28, 2018, in which tyrosine-kinase inhibitors had not been given as a first-line treatment. Patients from 14 European, North American, and Asia-Pacific study groups of the Ponte di Legno group were included. No patients were excluded, and patients were followed up by individual study groups. Through the Ponte di Legno group, we collected data on the baseline characteristics of patients, including IKZF1, PAX5, and CDKN2A/B deletion status, and whether haematopoietic stem cell transplantation (HSCT) had been done, as well as treatment outcomes, including complete remission, no response, relapse, early death, and treatment-related mortality, response to prednisone, and minimal residual disease (MRD) at end of induction therapy. 5-year event-free survival and 5-year overall survival were estimated by use of Kaplan-Meier methods, and the 5-year cumulative incidence of relapse was calculated by use of a competing risk model. Findings: We identified 122 paediatric patients with newly diagnosed ABL-class fusion B-cell acute lymphocytic leukaemia (77 from European study groups, 25 from North American study groups, and 20 from Asia-Pacific study groups). 64 (52%) of 122 patients were PDGFRB fusion-positive, 40 (33%) were ABL1 fusion-positive, ten (8%) were CSF1R fusion-positive, and eight (7%) were ABL2 fusion-positive. In all 122 patients, 5-year event-free survival was 59·1% (95% CI 50·5–69·1), 5-year overall survival was 76·1% (68·6–84·5), and the 5-year cumulative incidence of relapse was 31·0% (95% CI 22·4–40·1). MRD at the end of induction therapy was high (≥10−2 cells) in 61 (66%) of 93 patients, and most prevalent in patients with ABL2 fusions (six [86%] of 7 patients) and PDGFRB fusion-positive B-cell acute lymphocytic leukaemia (43 [88%] of 49 patients). MRD at the end of induction therapy of 10−2 cells or more was predictive of an unfavourable outcome (hazard ratio of event-free survival in patients with a MRD of ≥10−2 vs those with a MRD of
- Subjects :
- Male
medicine.medical_specialty
Adolescent
Oncogene Proteins, Fusion
Fusion Proteins, bcr-abl
Protein Kinase Inhibitor
Disease-Free Survival
Article
Follow-Up Studie
Cohort Studies
03 medical and health sciences
0302 clinical medicine
Allograft
Protein-Tyrosine Kinase
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
hemic and lymphatic diseases
Internal medicine
medicine
Humans
Cumulative incidence
Progression-free survival
Proto-Oncogene Proteins c-abl
Child
Protein Kinase Inhibitors
Retrospective Studies
B-Lymphocytes
business.industry
Hematopoietic Stem Cell Transplantation
Infant
Cancer
Retrospective cohort study
Hematology
Protein-Tyrosine Kinases
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Allografts
medicine.disease
Pediatric cancer
Minimal residual disease
Progression-Free Survival
Transplantation
Child, Preschool
030220 oncology & carcinogenesis
Tyrosine
Female
business
Follow-Up Studies
Human
030215 immunology
Cohort study
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Lancet Haematol
- Accession number :
- edsair.doi.dedup.....269fe3b4e89e11911b620770eabb0503