Dexamethasone/vincristine pulses significantly reduce administered doses of 6MP/MTX during maintenance therapy in childhood acute lymphoblastic leukemia

Background: Maintenance therapy with 6-Mercaptopurine (6MP) and Methotrexate (MTX) with or without dexamethasone (DEX) and vincristine (VCR) pulses, is crucial in childhood acute lymphoblastic leukaemia (ALL). Dosing adjustments are based on white blood cell (WBC) and neutrophil counts (ANC) to balance relapse and infection risks. We investigated if clinicians adjust doses for high versus low WBC/ANC and how pulses affect WBC/ANC and dose intensity. Methods: Analyzing WBC/ANC and 6MP/MTX doses in DCOG-ALL11 (ALL11) and ALLtogether (A2G) patients, we assessed clinical compliance with dose-adjustment guidelines. Results: Across 2901 WBC checkpoints in ALL11 and 3806 in A2G (validation cohort), clinicians were non-compliant with dose-adjustment guidelines in 44 % (ALL11) and 31 % (A2G) of cases. At checkpoints where no-compliance was observed, WBC/ANC levels were most frequently above target (85.1 % in ALL11 and 87.7 % in A2G) and rarely below (6.4 % in ALL11 and 6.7 % in A2G, p < 0.001).Median WBC/ANC levels often exceeded recommendations (3.1 and 1.6 ×109/L, respectively) and patients receiving DEX/VCR pulses had a lower median dose 6MP / MTX (60 %) than those without pulses (100 % ALL11, 75 % A2G; P < 0.001), resulting in lower absolute doses. Conclusions: In conclusion, clinicians are less likely to adjust doses properly when WBC/ANC levels exceed targets, reducing 6MP/MTX dose intensity. DEX/VCR pulses significantly lower 6MP/MTX doses, possibly influencing their benefit in ALL maintenance.