High-dose methotrexate was not associated with a reduction in the risk for CNS relapse compared with standard interim maintenance therapy in children and young adults with acute lymphoblastic leukemia (ALL) who were enrolled in the phase 3 UKALL 2011 trial.


The UKALL 2011 trial included children and young adults aged 25 or younger with ALL to investigate the difference of a short (14 days) versus a standard (28 days) induction course of dexamethasone, the CNS relapse risk for high-dose methotrexate compared with a standard interim maintenance regimen, and the difference between the effect of vincristine/dexamethasone pulses or no pulses on bone marrow relapse rate. At ASH 2017, the results for the dexamethasone induction courses were presented.1 Amy Kirkwood (University College London, UK) presented the maintenance results2 at the 2022 annual meeting of the American Society of Hematology.

In total, 1,570 participants receiving backbone therapy according to the risk group to which they were stratified were randomized to one of four maintenance arms:

  • High-dose methotrexate with pulses
  • High-dose methotrexate without pulses
  • Standard interim maintenance with pulses
  • Standard interim maintenance without pulses

After a median follow-up of 72 months, there was no difference between high-dose methotrexate or standard interim maintenance with regard to CNS relapse (HR, 0.99; 95% CI, 0.65-1.51; P=0.97), with 5-year rates of 5.6% for both treatment regimens. Interestingly, participants who received a short course of induction dexamethasone followed by high-dose methotrexate and no pulses had an inferior event-free survival compared with participants who received short-duration induction dexamethasone followed by either high-dose methotrexate with pulses or standard interim maintenance with or without pulses (survival rate, 75.9% vs 83.2% to 86.0%; P value for interaction=0.006).

Furthermore, “no pulses” was non-inferior to “pulses” regarding bone marrow relapse rates (HR, 1.22; 95% CI, 0.89-1.67). The corresponding 5-year bone marrow relapse rates were 12.2% for participants who did not receive pulses and 10.2% for those who did. Kirkwood added that the 5-year event-free survival rate was slightly higher in participants who received pulses compared with participants who did not receive pulses (86.0% vs 81.7%; P=0.010).

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