-
Something wrong with this record ?
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
C. Eckert, C. Parker, AV. Moorman, JA. Irving, R. Kirschner-Schwabe, S. Groeneveld-Krentz, T. Révész, P. Hoogerbrugge, J. Hancock, R. Sutton, G. Henze, C. Chen-Santel, A. Attarbaschi, JP. Bourquin, L. Sramkova, M. Zimmermann, S. Krishnan, A. von...
Language English Country Great Britain
Document type Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't
Grant support
A6791
Cancer Research UK - United Kingdom
- MeSH
- Time Factors MeSH
- Child MeSH
- Progression-Free Survival MeSH
- Gene Dosage MeSH
- Risk Assessment MeSH
- Karyotype MeSH
- Clinical Trials as Topic MeSH
- Humans MeSH
- Precursor T-Cell Lymphoblastic Leukemia-Lymphoma diagnosis genetics mortality therapy MeSH
- Adolescent MeSH
- Mutation MeSH
- Biomarkers, Tumor genetics MeSH
- Graft vs Host Disease etiology MeSH
- Precursor B-Cell Lymphoblastic Leukemia-Lymphoma diagnosis genetics mortality therapy MeSH
- Child, Preschool MeSH
- Disease-Free Survival MeSH
- Disease Progression MeSH
- Antineoplastic Combined Chemotherapy Protocols adverse effects therapeutic use MeSH
- Recurrence MeSH
- Neoplasm, Residual MeSH
- Risk Factors MeSH
- Hematopoietic Stem Cell Transplantation * adverse effects MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
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.
Department of Pediatric Hematology and Oncology Hannover Medical School Hannover Germany
Department of Pediatric Oncology Hematology Charité Universitätsmedizin Berlin Berlin Germany
Department of Pediatric Oncology University Children's Hospital Zurich Switzerland
German Cancer Consortium and German Cancer Research Center Im Neuenheimer Feld Heidelberg Germany
Southmead Hospital Bristol Genetics Laboratory Bristol UK
Tata Translational Cancer Research Centre Tata Medical Center New Town Kolkata India
University Children's Hospital University Medical Center Rostock Rostock Germany
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc22004130
- 003
- CZ-PrNML
- 005
- 20220127145504.0
- 007
- ta
- 008
- 220113s2021 xxk f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/j.ejca.2021.03.034 $2 doi
- 035 __
- $a (PubMed)34010787
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxk
- 100 1_
- $a Eckert, Cornelia $u 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
- 245 10
- $a 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 / $c C. Eckert, C. Parker, AV. Moorman, JA. Irving, R. Kirschner-Schwabe, S. Groeneveld-Krentz, T. Révész, P. Hoogerbrugge, J. Hancock, R. Sutton, G. Henze, C. Chen-Santel, A. Attarbaschi, JP. Bourquin, L. Sramkova, M. Zimmermann, S. Krishnan, A. von Stackelberg, V. Saha
- 520 9_
- $a 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.
- 650 _2
- $a mladiství $7 D000293
- 650 _2
- $a protokoly protinádorové kombinované chemoterapie $x škodlivé účinky $x terapeutické užití $7 D000971
- 650 _2
- $a nádorové biomarkery $x genetika $7 D014408
- 650 _2
- $a dítě $7 D002648
- 650 _2
- $a předškolní dítě $7 D002675
- 650 _2
- $a klinické zkoušky jako téma $7 D002986
- 650 _2
- $a progrese nemoci $7 D018450
- 650 _2
- $a přežití bez známek nemoci $7 D018572
- 650 _2
- $a ženské pohlaví $7 D005260
- 650 _2
- $a genová dávka $7 D018628
- 650 _2
- $a nemoc štěpu proti hostiteli $x etiologie $7 D006086
- 650 12
- $a transplantace hematopoetických kmenových buněk $x škodlivé účinky $7 D018380
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a karyotyp $7 D059785
- 650 _2
- $a mužské pohlaví $7 D008297
- 650 _2
- $a mutace $7 D009154
- 650 _2
- $a reziduální nádor $7 D018365
- 650 _2
- $a pre-B-buněčná leukemie $x diagnóza $x genetika $x mortalita $x terapie $7 D015452
- 650 _2
- $a lymfoblastická leukemie-lymfom z prekurzorových T-buněk $x diagnóza $x genetika $x mortalita $x terapie $7 D054218
- 650 _2
- $a doba přežití bez progrese choroby $7 D000077982
- 650 _2
- $a recidiva $7 D012008
- 650 _2
- $a hodnocení rizik $7 D018570
- 650 _2
- $a rizikové faktory $7 D012307
- 650 _2
- $a časové faktory $7 D013997
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a multicentrická studie $7 D016448
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Parker, Catriona $u 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
- 700 1_
- $a Moorman, Anthony V $u Wolfson Childhood Cancer Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
- 700 1_
- $a Irving, Julie Ae $u Wolfson Childhood Cancer Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
- 700 1_
- $a Kirschner-Schwabe, Renate $u Department of Pediatric Oncology Hematology, Charité - Universitätsmedizin Berlin, Berlin, Germany; German Cancer Consortium, and German Cancer Research Center, Im Neuenheimer Feld, Heidelberg, Germany
- 700 1_
- $a Groeneveld-Krentz, Stefanie $u Department of Pediatric Oncology Hematology, Charité - Universitätsmedizin Berlin, Berlin, Germany
- 700 1_
- $a Révész, Tamas $u Department of Hematology-Oncology, SA Pathology at Women's and Children's Hospital and University of Adelaide, Adelaide, Australia
- 700 1_
- $a Hoogerbrugge, Peter $u Princess Maxima Center for Pediatric Oncology, Utrecht, and Dutch Childhood Oncology Group, Utrecht, the Netherlands
- 700 1_
- $a Hancock, Jeremy $u Southmead Hospital Bristol Genetics Laboratory, Bristol, UK
- 700 1_
- $a Sutton, Rosemary $u Children's Cancer Institute, School of Women's and Children's Health, University of New South Wales, Sydney, Australia
- 700 1_
- $a Henze, Guenter $u Department of Pediatric Oncology Hematology, Charité - Universitätsmedizin Berlin, Berlin, Germany
- 700 1_
- $a Chen-Santel, Christiane $u Department of Pediatric Oncology Hematology, Charité - Universitätsmedizin Berlin, Berlin, Germany; University Children's Hospital, University Medical Center Rostock, Rostock, Germany
- 700 1_
- $a Attarbaschi, Andishe $u St Anna Children's Research Institute and Children's Hospital, Medical University of Vienna, Vienna, Austria
- 700 1_
- $a Bourquin, Jean-Pierre $u Department of Pediatric Oncology, University Children's Hospital, Zurich, Switzerland
- 700 1_
- $a Sramkova, Lucie $u Department of Pediatric Hematology and Oncology, Charles University, 2nd Medical School and University Hospital Motol, Prague, Czech Republic
- 700 1_
- $a Zimmermann, Martin $u Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
- 700 1_
- $a Krishnan, Shekhar $u 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
- 700 1_
- $a von Stackelberg, Arend $u Department of Pediatric Oncology Hematology, Charité - Universitätsmedizin Berlin, Berlin, Germany
- 700 1_
- $a Saha, Vaskar $u 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
- 773 0_
- $w MED00009626 $t European journal of cancer (Oxford, England : 1990) $x 1879-0852 $g Roč. 151, č. - (2021), s. 175-189
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/34010787 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y p $z 0
- 990 __
- $a 20220113 $b ABA008
- 991 __
- $a 20220127145500 $b ABA008
- 999 __
- $a ok $b bmc $g 1751560 $s 1155279
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2021 $b 151 $c - $d 175-189 $e 20210516 $i 1879-0852 $m European journal of cancer $n Eur J Cancer $x MED00009626
- GRA __
- $a A6791 $p Cancer Research UK $2 United Kingdom
- LZP __
- $a Pubmed-20220113
