GRAALL-2005: randomised hyperfractionated cyclophosphamide in a paediatric-inspired adult ALL protocol
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.
Overview
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).
- 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).
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.
- Patients aged 55 and over, who tolerated the protocol worst, were the only group in which hyperfractionated cyclophosphamide appeared to help.
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