Recent trials show 5-year survival rates >95% for ETV6::RUNX1 Acute Lymphoblastic Leukemia (ALL). Since treatment has many side effects, an overview of cumulative drug doses and intensities between eight international trials is presented to characterize therapy needed for cure. A meta-analysis was performed as a comprehensive summary of survival outcomes at 5 and 10 years. For drug dose comparison in non-high risk trial arms, risk group distribution was applied to split the trials into two groups: trial group A with ~70% (range: 63.5-75%) of patients in low risk (LR) (CCLSG ALL2004, CoALL 07-03, NOPHO ALL2008, UKALL2003) and trial group B with ~45% (range: 38.7-52.7%) in LR (AIEOP-BFM ALL 2000, ALL-IC BFM ALL 2002, DCOG ALL10, JACLS ALL-02). Meta-analysis did not show evidence of heterogeneity between studies in trial group A LR and medium risk (MR) despite differences in treatment intensity. Statistical heterogeneity was present in trial group B LR and MR. Trials using higher cumulative dose and intensity of asparaginase and pulses of glucocorticoids and vincristine showed better 5-year event-free survival but similar overall survival. Based on similar outcomes between trials despite differences in therapy intensity, future trials should investigate, to what extent de-escalation is feasible for ETV6::RUNX1 ALL.

Associazione Italiana di Ematologia e Oncologia Pediatrica Bologna Italy

Berlin Frankfurt Münster Study Group Frankfurt Germany

Childhood Acute Lymphoblastic Leukemia study group Hamburg Germany

Childhood Cancer Research Unit Department of Women's and Children's Health Karolinska Institutet Stockholm Sweden

Children's Cancer and Leukemia Study Group Nagoya Japan

Department of Biomedical Science Section Medical Statistics Leiden University Medical Center Leiden The Netherlands

Department of Haematology Great Ormond Street Hospital London UK

Department of Paediatric Haematology and Oncology Hannover Medical School 30625 Hannover Germany

Department of Paediatric Oncology Karolinska University Hospital Stockholm Sweden

Department of Paediatrics University Medical Centre Schleswig Holstein Kiel Germany

Department of Pediatric Hematology and Oncology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Pediatric Hematology and Oncology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Pediatrics and Adolescent Medicine University Hospital Rigshospitalet Institute of Clinical Medicine Faculty of Medicine University of Copenhagen Copenhagen Denmark

Department of Pediatrics Kyoto Prefectural University of Medicine Graduate School of Medical Science Kyoto Japan

Department of Pediatrics Niigata University Graduate School of Medical and Dental Sciences Niigata Japan

Department of Pediatrics University of Milano Bicocca Monza Italy

Dutch Childhood Oncology Group Utrecht The Netherlands

Japan Childhood Leukemia Study Group Nagoya Japan

Leukaemia Research Cytogenetics Group Translational and Clinical Research Institute Newcastle University Newcastle upon Tyne UK

Mathematical Institute Leiden University Leiden The Netherlands

Nordic Society of Paediatric Haematology and Oncology Nordic and Baltic Countries Uppsala Sweden

Nordic Society of Paediatric Haematology and Oncology Nordic Countries Uppsala Sweden

Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands

United Kingdom Acute Lymphoblastic Leukaemia study group Liverpool UK

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