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
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't
Grant support
10060
Blood Cancer UK - United Kingdom
12026
Blood Cancer UK - United Kingdom
15014
Blood Cancer UK - United Kingdom
A6791
Cancer Research UK - United Kingdom
PubMed
34010787
DOI
10.1016/j.ejca.2021.03.034
PII: S0959-8049(21)00201-X
Knihovny.cz E-resources
- Keywords
- Acute lymphoblastic leukaemia, High-risk, Minimal residual disease, Outcomes, Stem cell transplantation,
- 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
- Names of Substances
- Biomarkers, Tumor 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
References provided by Crossref.org
ClinicalTrials.gov
NCT00114348, NCT00967057
