Cornelia Eckert1, Catriona Parker2, Anthony V Moorman3, Julie Ae Irving3, Renate Kirschner-Schwabe4, Stefanie Groeneveld-Krentz5, Tamas Révész6, Peter Hoogerbrugge7, Jeremy Hancock8, Rosemary Sutton9, Guenter Henze5, Christiane Chen-Santel10, Andishe Attarbaschi11, Jean-Pierre Bourquin12, Lucie Sramkova13, Martin Zimmermann14, Shekhar Krishnan15, Arend von Stackelberg5, Vaskar Saha16. 1. Department of Pediatric Oncology Hematology, Charité - Universitätsmedizin Berlin, Berlin, Germany; German Cancer Consortium, and German Cancer Research Center, Im Neuenheimer Feld, Heidelberg, Germany. Electronic address: cornelia.eckert@charite.de. 2. Children's Cancer Group, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, UK. 3. Wolfson Childhood Cancer Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK. 4. Department of Pediatric Oncology Hematology, Charité - Universitätsmedizin Berlin, Berlin, Germany; German Cancer Consortium, and German Cancer Research Center, Im Neuenheimer Feld, Heidelberg, Germany. 5. Department of Pediatric Oncology Hematology, Charité - Universitätsmedizin Berlin, Berlin, Germany. 6. Department of Hematology-Oncology, SA Pathology at Women's and Children's Hospital and University of Adelaide, Adelaide, Australia. 7. Princess Maxima Center for Pediatric Oncology, Utrecht, and Dutch Childhood Oncology Group, Utrecht, the Netherlands. 8. Southmead Hospital Bristol Genetics Laboratory, Bristol, UK. 9. Children's Cancer Institute, School of Women's and Children's Health, University of New South Wales, Sydney, Australia. 10. Department of Pediatric Oncology Hematology, Charité - Universitätsmedizin Berlin, Berlin, Germany; University Children's Hospital, University Medical Center Rostock, Rostock, Germany. 11. St Anna Children's Research Institute and Children's Hospital, Medical University of Vienna, Vienna, Austria. 12. Department of Pediatric Oncology, University Children's Hospital, Zurich, Switzerland. 13. Department of Pediatric Hematology and Oncology, Charles University, 2nd Medical School and University Hospital Motol, Prague, Czech Republic. 14. Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany. 15. Children's Cancer Group, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, UK; Tata Translational Cancer Research Centre, Tata Medical Center, New Town, Kolkata, India. 16. Children's Cancer Group, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, UK; Tata Translational Cancer Research Centre, Tata Medical Center, New Town, Kolkata, India. Electronic address: v.saha@manchester.ac.uk.
Abstract
AIM: Outcomes of children with high-risk (HR) relapsed acute lymphoblastic leukaemia (ALL) (N = 393), recruited to ALLR3 and ALL-REZ BFM 2002 trials, were analysed. Minimal residual disease (MRD) was assessed after induction and at predetermined time points until haematopoietic stem cell transplantation (SCT). METHODS: Genetic analyses included karyotype, copy-number alterations and mutation analyses. Ten-year survivals were analysed using Kaplan-Meier and Cox models for multivariable analyses. RESULTS: Outcomes of patients were comparable in ALLR3 and ALL-REZ BFM 2002. The event-free survival of B-cell precursor (BCP) and T-cell ALL (T-ALL) was 22.6% and 26.2% (P = 0.94), respectively, and the overall survival (OS) was 32.6% and 28.2% (P = 0.11), respectively. Induction failures (38%) were associated with deletions of NR3C1 (P = 0.002) and BTG1 (P = 0.03) in BCP-ALL. The disease-free survival (DFS) and OS in patients with good vs poor MRD responses were 57.4% vs 22.6% (P < 0.0001) and 57.8% vs 32.0% (P = 0.0004), respectively. For BCP- and T-ALL, the post-SCT DFS and OS were 42.1% and 56.8% (P = 0.26) and 51.6% and 55.4% (P = 0.67), respectively. The cumulative incidences of post-SCT relapse for BCP- and T-ALL were 36.9% and 17.8% (P = 0.012) and of death were 10.7% and 25.5% (P = 0.013), respectively. Determinants of outcomes after SCT were acute graft versus host disease, pre-SCT MRD (≥10-3), HR cytogenetics and TP53 alterations in BCP-ALL. CONCLUSION: Improvements in outcomes for HR ALL relapses require novel compounds in induction therapy to improve remission rates and immune targeted therapy after induction to maintain remission after SCT. TRIAL REGISTRATION: ALLR3: NCT00967057; ALL REZ-BFM 2002: NCT00114348.
AIM: Outcomes of children with high-risk (HR) relapsed acute lymphoblastic leukaemia (ALL) (N = 393), recruited to ALLR3 and ALL-REZ BFM 2002 trials, were analysed. Minimal residual disease (MRD) was assessed after induction and at predetermined time points until haematopoietic stem cell transplantation (SCT). METHODS: Genetic analyses included karyotype, copy-number alterations and mutation analyses. Ten-year survivals were analysed using Kaplan-Meier and Cox models for multivariable analyses. RESULTS: Outcomes of patients were comparable in ALLR3 and ALL-REZ BFM 2002. The event-free survival of B-cell precursor (BCP) and T-cell ALL (T-ALL) was 22.6% and 26.2% (P = 0.94), respectively, and the overall survival (OS) was 32.6% and 28.2% (P = 0.11), respectively. Induction failures (38%) were associated with deletions of NR3C1 (P = 0.002) and BTG1 (P = 0.03) in BCP-ALL. The disease-free survival (DFS) and OS in patients with good vs poor MRD responses were 57.4% vs 22.6% (P < 0.0001) and 57.8% vs 32.0% (P = 0.0004), respectively. For BCP- and T-ALL, the post-SCT DFS and OS were 42.1% and 56.8% (P = 0.26) and 51.6% and 55.4% (P = 0.67), respectively. The cumulative incidences of post-SCT relapse for BCP- and T-ALL were 36.9% and 17.8% (P = 0.012) and of death were 10.7% and 25.5% (P = 0.013), respectively. Determinants of outcomes after SCT were acute graft versus host disease, pre-SCT MRD (≥10-3), HR cytogenetics and TP53 alterations in BCP-ALL. CONCLUSION: Improvements in outcomes for HR ALL relapses require novel compounds in induction therapy to improve remission rates and immune targeted therapy after induction to maintain remission after SCT. TRIAL REGISTRATION: ALLR3: NCT00967057; ALL REZ-BFM 2002: NCT00114348.
Authors: Tony H Truong; Cristian Jinca; Georg Mann; Smaranda Arghirescu; Jochen Buechner; Pietro Merli; James A Whitlock Journal: Front Pediatr Date: 2021-12-23 Impact factor: 3.418
Authors: Bianca A W Hoeben; Jeffrey Y C Wong; Lotte S Fog; Christoph Losert; Andrea R Filippi; Søren M Bentzen; Adriana Balduzzi; Lena Specht Journal: Front Pediatr Date: 2021-12-03 Impact factor: 3.418