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Objective To determine the incidence, serotype distribution and clinical outcomes of invasive pneumococcal disease (IPD) in children with acute lymphoblastic leukaemia (ALL) following widespread use of pneumococcal conjugate vaccines (PCVs).Design Multicentre cohort study.Setting Two tertiary paediatric oncology centres in Australia—Royal Children’s Hospital—Melbourne and Perth Children’s Hospital.Patients Children with cancer, including a defined subgroup with ALL.Interventions All children were assessed for provision of pneumococcal vaccines before and after their diagnosis of cancer.Main outcome measures Incidence of IPD in cancer (ALL and non-ALL) compared with the general paediatric population, serotype distribution, vaccination status and clinical outcomes.Results A total of 29 episodes of IPD in 28 children with cancer were included, of whom 19 had ALL. Less than a quarter had received additional pneumococcal vaccinations beyond the standard PCV schedule. The incidence of IPD in children with ALL was 190–360 times higher than in healthy children (1360 per 100 000 person-years). The majority of episodes (83%) were due to non-PCV13 serotypes, most commonly 23B. Clinical presentation was predominantly bacteraemia. Most patients recovered within 30 days, but there was one death attributable to IPD.Conclusions Children with ALL remain at substantially increased risk of IPD despite widespread PCV use, with disease largely caused by non-PCV13 serotypes. Uptake of additional pneumococcal doses was low. These findings underscore the need for optimised vaccination and prophylactic strategies in paediatric oncology populations.