Benefit of intensified treatment for all children with acute lymphoblasticleukaemia: results from MRC UKALL XI and MRC ALL97 randomised trials

Treatment of children with acute lymphoblastic leukaemia (ALL) aims to cure all patients with as little toxicity as possible and, if possible, to rest rict further intensification of chemotherapy to patients with an increased risk of relapse. However in Medical Research Council (MRC) trial UKALL X tw o short myeloablative blocks of intensification therapy given at weeks 5 an d 20 were of benefit to children in all risk groups. The successor trials, MRC UKALL XI and MRC ALL97, tested whether further intensification would co ntinue to benefit all patients by randomising them to receive, or not, an e xtended third intensification block at week 35. After a median follow-up of 4 years (range 5 months to 8 years), 5 year projected event-free survival was superior at 68% for the 894 patients allocated a third intensification compared with 60% for the 887 patients who did not receive one (odds ratio 0.75, 95% CI 0.63-0.90, 2P = 0.002). This difference was almost entirely du e to a reduced incidence of bone marrow relapses in the third intensificati on arm (140 of 891 in the third intensification arm vs 171 of 883 in the no third intensification, 2P = 0.02). Subgroup analysis suggests benefit of t he third intensification for all risk categories. Overall survival to date is no different in the two arms, indicating that a greater proportion of th ose not receiving a third intensification arm and subsequently relapsing ca n be salvaged. These results indicate that there is benefit of additional i ntensification for all risk subgroups of childhood ALL.