# GRAALL-2005: randomised hyperfractionated cyclophosphamide in a paediatric-inspired adult ALL protocol

Source: https://onco.cc/key-papers/paper-graall-2005-huguet-jco-2018/  
OnCo record `paper-graall-2005-huguet-jco-2018` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

The 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).

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Journal: Journal of Clinical Oncology
- Year: 2018
- DOI: 10.1200/JCO.2017.76.8192
- Authors: Huguet F, Chevret S, Leguay T, et al.
- 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).
- What it means: 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.

## Sources

- J Clin Oncol 2018: https://doi.org/10.1200/JCO.2017.76.8192
- PubMed: https://pubmed.ncbi.nlm.nih.gov/29863974/

## Connected records

- cancers: [Acute lymphoblastic leukaemia](https://onco.cc/cancers/all-leukemia/)
- drugs: [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/)
- trials: [GRAALL-2005](https://onco.cc/trials/graall-2005/)
- journals: [Journal of Clinical Oncology](https://onco.cc/journals/jco/)

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