title: Efficacy and toxicity of a paediatric protocol in teenagers and young adults with Philadelphia chromosome negative acute lymphoblastic leukaemia: results from UKALL 2003.
abstract: Despite the substantial outcome improvements achieved in paediatric acute lymphoblastic leukaemia (ALL), survival in teenage and young adult (TYA) patients has remained inferior. We report the treatment outcomes and toxicity profiles observed in TYA patients treated on the UK paediatric ALL trial, UKALL2003. UKALL2003 was a multi-centre, prospective, randomized phase III trial, investigating treatment intensification or de-escalation according to minimal residual disease (MRD) kinetics at the end of induction. Of 3126 patients recruited to UKALL2003, 229 (7·3%) were aged 16-24 years. These patients were significantly more likely to have high risk MRD compared to 10-15 year olds (47·9% vs. 36·6%, P = 0·004). Nonetheless, 5-year event-free survival for the TYA cohort (aged 16-24 years) was 72·3% [95% confidence interval (CI): 66·2-78·4] overall and 92·6% (95% CI: 85·5-99·7) for MRD low risk patients. The risk of serious adverse events was higher in patients aged ≥10 years compared to those aged 9 or younger (P < 0·0001) and novel age-specific patterns of treatment-related toxicity were observed. TYA patients obtain excellent outcomes with a risk- and response-adapted paediatric chemotherapy protocol. Whilst those aged 10 years and older have excess toxicity compared with younger patients, the age association is specific to individual toxicities.
authors.affiliation: University College Hospital, London, UK.
authors.forename: Rachael
authors.initials: R
authors.lastname: Hough
authors.affiliation: University Hospital of Wales, Cardiff, UK.
authors.forename: Clare
authors.initials: C
authors.lastname: Rowntree
authors.affiliation: Great Ormond Street Hospital, London, UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Goulden
authors.affiliation: John Radcliffe Hospital, Oxford, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Mitchell
authors.affiliation: Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Anthony
authors.initials: A
authors.lastname: Moorman
authors.affiliation: Clinical Trial Service Unit, University of Oxford, Oxford, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Wade
authors.affiliation: Sheffield Children's Hospital, Sheffield, UK.
authors.forename: Ajay
authors.initials: A
authors.lastname: Vora
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000009:adverse effects; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D018365:Neoplasm, Residual; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018570:Risk Assessment / Q000379:methods; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
chemical_list: D014750:Vincristine; D003907:Dexamethasone; D015122:Mercaptopurine; D001215:Asparaginase; D008727:Methotrexate; D003630:Daunorubicin
keywords: acute lymphoblastic leukaemia; chemotherapy; efficacy; teenage and young adult; toxicity