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Outcomes of patients with childhood B-cell precursor acute lymphoblastic leukaemia with late bone marrow relapses: long-term follow-up of the ALLR3 open-label randomised trial.

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SUBMITTER: Parker C

PROVIDER: S-EPMC6445853 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Outcomes of patients with childhood B-cell precursor acute lymphoblastic leukaemia with late bone marrow relapses: long-term follow-up of the ALLR3 open-label randomised trial.

Parker Catriona C Krishnan Shekhar S Hamadeh Lina L Irving Julie A E JAE Kuiper Roland P RP Révész Tamas T Hoogerbrugge Peter P Hancock Jeremy J Sutton Rosemary R Moorman Anthony V AV Saha Vaskar V

The Lancet. Haematology 20190227 4

<h4>Background</h4>The ALLR3 trial investigated outcomes of children with B-cell precursor acute lymphoblastic leukaemia who had late bone marrow relapses. We analysed long-term follow-up outcomes of these patients.<h4>Methods</h4>ALLR3 was an open-label randomised clinical trial that recruited children aged 1-18 years with B-cell precursor acute lymphoblastic leukaemia who had late bone marrow relapses. Eligible patients were recruited from centres in Australia, Ireland, the Netherlands, New Ze ...[more]

PMID: 30826273

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Project description:BackgroundAbout a fifth of children with acute T-lymphoblastic leukaemia (T-ALL) succumb to the disease, suggesting an unrecognised biological heterogeneity that might contribute to drug resistance. We postulated that T-ALL originating from early T-cell precursors (ETPs), a recently defined subset of thymocytes that retain stem-cell-like features, would respond poorly to lymphoid-cell-directed therapy. We studied leukaemic cells, collected at diagnosis, to identify cases with ETP features and determine their clinical outcome.MethodsLeukaemic cells from 239 patients with T-ALL enrolled at St Jude Children's Research Hospital (n=139) and in the Italian national study Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) ALL-2000 (n=100) were assessed by gene-expression profiling, flow cytometry, and single nucleotide polymorphism array analysis. Probabilities of survival and treatment failure were calculated for subgroups considered to have ETP-ALL or typical T-ALL.Findings30 patients (12.6%) had leukaemic lymphoblasts with an ETP-related gene-expression signature or its associated distinctive immunophenotype (CD1a(-), CD8(-), CD5(weak) with stem-cell or myeloid markers). Cases of ETP-ALL showed increased genomic instability, in terms of number and size of gene lesions, compared with those with typical T-ALL. Patients with this form of leukaemia had high risk of remission failure or haematological relapse (72% [95% CI 40-100] at 10 years vs 10% [4-16] at 10 years for patients with typical T-ALL treated at St Jude Children's Research Hospital; and 57% [25-89] at 2 years vs 14% [6-22] at 2 years for patients treated in the AIEOP trial).InterpretationETP-ALL is a distinct, previously unrecognised, pathobiological entity that confers a poor prognosis with use of standard intensive chemotherapy. Its early recognition, by use of the gene expression and immunophenotypic criteria outlined here, is essential for the development of an effective clinical management strategy.FundingUS National Cancer Institute, Cariplo Foundation, Citta della Speranza Foundation, Italian Association for Cancer Research (AIRC), Italian Ministry for University and Research, and American Lebanese Syrian Associated Charities (ALSAC).

Dataset Information

Outcomes of patients with childhood B-cell precursor acute lymphoblastic leukaemia with late bone marrow relapses: long-term follow-up of the ALLR3 open-label randomised trial.

Publications

Outcomes of patients with childhood B-cell precursor acute lymphoblastic leukaemia with late bone marrow relapses: long-term follow-up of the ALLR3 open-label randomised trial.

Similar Datasets

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