PMID- 34010787 OWN - NLM STAT- MEDLINE DCOM- 20211108 LR - 20230913 IS - 1879-0852 (Electronic) IS - 0959-8049 (Linking) VI - 151 DP - 2021 Jul TI - Risk factors and outcomes in children with high-risk B-cell precursor and T-cell relapsed acute lymphoblastic leukaemia: combined analysis of ALLR3 and ALL-REZ BFM 2002 clinical trials. PG - 175-189 LID - S0959-8049(21)00201-X [pii] LID - 10.1016/j.ejca.2021.03.034 [doi] AB - 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. CI - Copyright (c) 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved. FAU - Eckert, Cornelia AU - Eckert C AD - Department of Pediatric Oncology Hematology, Charite - Universitatsmedizin Berlin, Berlin, Germany; German Cancer Consortium, and German Cancer Research Center, Im Neuenheimer Feld, Heidelberg, Germany. Electronic address: cornelia.eckert@charite.de. FAU - Parker, Catriona AU - Parker C AD - 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. FAU - Moorman, Anthony V AU - Moorman AV AD - Wolfson Childhood Cancer Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK. FAU - Irving, Julie Ae AU - Irving JA AD - Wolfson Childhood Cancer Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK. FAU - Kirschner-Schwabe, Renate AU - Kirschner-Schwabe R AD - Department of Pediatric Oncology Hematology, Charite - Universitatsmedizin Berlin, Berlin, Germany; German Cancer Consortium, and German Cancer Research Center, Im Neuenheimer Feld, Heidelberg, Germany. FAU - Groeneveld-Krentz, Stefanie AU - Groeneveld-Krentz S AD - Department of Pediatric Oncology Hematology, Charite - Universitatsmedizin Berlin, Berlin, Germany. FAU - Revesz, Tamas AU - Revesz T AD - Department of Hematology-Oncology, SA Pathology at Women's and Children's Hospital and University of Adelaide, Adelaide, Australia. FAU - Hoogerbrugge, Peter AU - Hoogerbrugge P AD - Princess Maxima Center for Pediatric Oncology, Utrecht, and Dutch Childhood Oncology Group, Utrecht, the Netherlands. FAU - Hancock, Jeremy AU - Hancock J AD - Southmead Hospital Bristol Genetics Laboratory, Bristol, UK. FAU - Sutton, Rosemary AU - Sutton R AD - Children's Cancer Institute, School of Women's and Children's Health, University of New South Wales, Sydney, Australia. FAU - Henze, Guenter AU - Henze G AD - Department of Pediatric Oncology Hematology, Charite - Universitatsmedizin Berlin, Berlin, Germany. FAU - Chen-Santel, Christiane AU - Chen-Santel C AD - Department of Pediatric Oncology Hematology, Charite - Universitatsmedizin Berlin, Berlin, Germany; University Children's Hospital, University Medical Center Rostock, Rostock, Germany. FAU - Attarbaschi, Andishe AU - Attarbaschi A AD - St Anna Children's Research Institute and Children's Hospital, Medical University of Vienna, Vienna, Austria. FAU - Bourquin, Jean-Pierre AU - Bourquin JP AD - Department of Pediatric Oncology, University Children's Hospital, Zurich, Switzerland. FAU - Sramkova, Lucie AU - Sramkova L AD - Department of Pediatric Hematology and Oncology, Charles University, 2nd Medical School and University Hospital Motol, Prague, Czech Republic. FAU - Zimmermann, Martin AU - Zimmermann M AD - Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany. FAU - Krishnan, Shekhar AU - Krishnan S AD - 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. FAU - von Stackelberg, Arend AU - von Stackelberg A AD - Department of Pediatric Oncology Hematology, Charite - Universitatsmedizin Berlin, Berlin, Germany. FAU - Saha, Vaskar AU - Saha V AD - 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. LA - eng SI - ClinicalTrials.gov/NCT00114348 SI - ClinicalTrials.gov/NCT00967057 GR - 10060/LLR_/Blood Cancer UK/United Kingdom GR - 12026/LLR_/Blood Cancer UK/United Kingdom GR - 15014/LLR_/Blood Cancer UK/United Kingdom GR - A6791/CRUK_/Cancer Research UK/United Kingdom PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20210516 PL - England TA - Eur J Cancer JT - European journal of cancer (Oxford, England : 1990) JID - 9005373 RN - 0 (Biomarkers, Tumor) SB - IM MH - Adolescent MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Biomarkers, Tumor/genetics MH - Child MH - Child, Preschool MH - Clinical Trials as Topic MH - Disease Progression MH - Disease-Free Survival MH - Female MH - Gene Dosage MH - Graft vs Host Disease/etiology MH - *Hematopoietic Stem Cell Transplantation/adverse effects MH - Humans MH - Karyotype MH - Male MH - Mutation MH - Neoplasm, Residual MH - Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis/genetics/mortality/*therapy MH - Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis/genetics/mortality/*therapy MH - Progression-Free Survival MH - Recurrence MH - Risk Assessment MH - Risk Factors MH - Time Factors OTO - NOTNLM OT - Acute lymphoblastic leukaemia OT - High-risk OT - Minimal residual disease OT - Outcomes OT - Stem cell transplantation COIS- Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article. EDAT- 2021/05/20 06:00 MHDA- 2021/11/09 06:00 CRDT- 2021/05/19 20:15 PHST- 2020/12/31 00:00 [received] PHST- 2021/03/01 00:00 [revised] PHST- 2021/03/15 00:00 [accepted] PHST- 2021/05/20 06:00 [pubmed] PHST- 2021/11/09 06:00 [medline] PHST- 2021/05/19 20:15 [entrez] AID - S0959-8049(21)00201-X [pii] AID - 10.1016/j.ejca.2021.03.034 [doi] PST - ppublish SO - Eur J Cancer. 2021 Jul;151:175-189. doi: 10.1016/j.ejca.2021.03.034. Epub 2021 May 16.