Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic eff ects. This is because reported frequencies vary widely across studies, partly because of diverse defi nitions of toxic eff ects. Using the Delphi method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic eff ects that were to be considered by the Ponte di Legno working group. 14 acute toxic eff ects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis, asparaginase-associated pancreatitis, arterial hypertension, posterior reversible encephalopathy syndrome, seizures, depressed level of consciousness, methotrexate-related stroke-like syndrome, peripheral neuropathy, high-dose methotrexate-related nephrotoxicity, sinusoidal obstructive syndrome, thrombo embolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus defi nitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14 toxic eff ects, that no two protocols shared identical defi nitions of all toxic eff ects, and that no toxic eff ect defi nition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus defi nitions were obtained for all 14 toxic eff ects. In the overall assessment of outcome of acute lymphoblastic leukaemia treatment, these expert opinion-based defi nitions will allow reliable comparisons of frequencies and severities of acute toxic eff ects across treatment protocols, and facilitate international research on cause, guidelines for treatment adaptation, preventive strategies, and development of consensus algorithms for reporting on acute lymphoblastic leukaemia treatment.
