Infectious Complications During Consolidation Therapy in Children with Acute Myeloid Leukemia (AML): A Review of Published Cohorts

Abstract

Children with acute myeloid leukaemia spend six to nine months neutropenic, and infection rather than leukaemia is what kills a substantial share of those who die in remission. Two consecutive multicentre trials from the same study group, a decade apart, provide an unusually clean comparison of what changed. Objectives: To review the published evidence on infectious complications during consolidation and other post-induction phases in children treated for acute myeloid leukaemia: how often they occur, which organisms are responsible, how mortality has changed between trial generations, and what prophylaxis has been shown to achieve.
Material and Methods: Narrative review of multicentre trial cohorts, registry analyses, randomised prophylaxis trials and practice guidelines indexed in PubMed and the major haematology and infectious disease journals. Studies were eligible if they reported infectious complications or infection-related mortality in a defined paediatric leukaemia population, or the effect of a prophylactic intervention. No new patient data were generated and no patients were recruited; every rate quoted is one published by the original investigators. Results: Across 304 children in one multicentre trial, 855 infectious episodes occurred, of which 61.2 per cent were fever without an identifiable source and 32.1 per cent were microbiologically documented; neutropenia was present in 74.1 per cent of episodes and 20 children died of infection-associated complications. In the successor trial enrolling 405 children a decade later, 1,326 infections occurred, averaging 3.3 per patient, but infection-related mortality fell from 5.4 to 1.5 per cent. Bloodstream isolates were predominantly Gram-positive (240 against 90 Gram-negative), with viridans group streptococci alone accounting for 112.
Invasive fungal infection affected 3 per cent of patients. Children with Down syndrome died of infection at 17.9 per cent against 5.4 per cent in those without. Conclusion: The number of infectious episodes did not fall between trial generations; the death rate did, by roughly two thirds. That pattern points to supportive care and earlier intervention rather than to infection prevention, and it means episode counts are a poor measure of whether a supportive care programme is working. Abbreviations: AML – Acute Myeloid Leukaemia, ALL – Acute Lymphoblastic Leukaemia, BFM – Berlin-Frankfurt-Münster, BSI – Bloodstream Infection,
CLABSI – Central Line-Associated Bloodstream Infection, CoNS – Coagulase-Negative Staphylococci, FUO – Fever of Unknown Origin, HAM – High-Dose Cytarabine and Mitoxantrone, IFI – Invasive Fungal Infection, VGS – Viridans Group Streptococci, HSCT – Haematopoietic Stem Cell Transplantation.