{"entity":{"id":"paper-graall-2005-huguet-jco-2018","kind":"paper","name":"GRAALL-2005: randomised hyperfractionated cyclophosphamide in a paediatric-inspired adult ALL protocol","aka":[],"tldr":"Treating adults up to 59 with a children's-style leukaemia protocol produced remission in nine out of ten and five-year survival near 60 percent, but intensifying cyclophosphamide added nothing and patients aged 55 and over tolerated the treatment poorly.","summary":"Report of the randomised GRAALL-2005 trial: 787 evaluable adults with newly diagnosed Philadelphia-negative acute lymphoblastic leukaemia (525 B-lineage, 262 T-lineage; median age 36) were randomised to standard-dose or hyperfractionated cyclophosphamide during induction and late intensification of a paediatric-inspired protocol.\n\nThe complete remission rate was 91.9 percent; five-year event-free survival was 52.2 percent and overall survival 58.5 percent. Hyperfractionated cyclophosphamide did not improve remission or survival. Age continuously worsened outcomes, with 55 years the best cut-off (five-year event-free survival 55.7 percent under 55 against 25.8 percent at 55 and over).","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2018","url":"https://doi.org/10.1200/JCO.2017.76.8192"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29863974/"}],"tags":[],"related":[],"cancers":["all-leukemia"],"sections":[],"technologies":[],"targets":[],"drugs":["cyclophosphamide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["graall-2005"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2018,"doi":"10.1200/JCO.2017.76.8192","pmid":"29863974","authors":"Huguet F, Chevret S, Leguay T, et al.","paperType":"rct","findings":["Complete remission 91.9 percent; five-year event-free survival 52.2 percent (95% CI 48.5 to 55.7) and overall survival 58.5 percent.","Hyperfractionated cyclophosphamide did not increase remission or prolong event-free or overall survival.","Five-year event-free survival 55.7 percent under age 55 versus 25.8 percent at 55 and over (hazard ratio 2.16, p < 0.001)."],"whatItMeans":"Paediatric-inspired protocols are the reference for younger adults with ALL, but their intensity is not tolerated from about age 55, which is where reduced-intensity and antibody-based approaches take over.","caveats":["Patients aged 55 and over, who tolerated the protocol worst, were the only group in which hyperfractionated cyclophosphamide appeared to help."],"changedPractice":false,"participants":787},"route":"/key-papers/paper-graall-2005-huguet-jco-2018/","neighbours":{"cancer":[{"id":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"}],"drug":[{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"}],"trial":[{"id":"graall-2005","kind":"trial","name":"GRAALL-2005","route":"/trials/graall-2005/"}],"journal":[{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","route":"/journals/jco/"}]}}