Dual direction associations between common autoimmune diseases and leukemia among children and young adults: A systematic review

Abstract

Background: Childhood leukemia and many autoimmune (AI) diseases are severe pediatric conditions with lifelong consequences. AI diseases form a heterogeneous disease group affecting about 5 % of children worldwide, while leukemia is the most common malignancy among children aged 0–14 years. The timing and similarities in suggested inflammatory and infectious triggers of AI disease and leukemia have raised a question whether the diseases share common etiological origins. We conducted a systematic review to evaluate the evidence linking childhood leukemia and AI diseases. Data sources: In the systematic literature search CINAHL (from 1970), Cochrane Library (form 1981), PubMed (from 1926) and Scopus (from 1948) were queried in June 2023. Review methods: We included studies covering the association between any AI disease and acute leukemia, limiting it to children and adolescents under 25 years old. The studies were reviewed independently by two researchers and the risk of bias was assessed. Results: A total of 2119 articles were screened and 253 studies were selected for detailed evaluation. Nine studies met the inclusion criteria, of which eight were cohort studies and one was a systematic review. The diseases covered were type 1 diabetes mellitus, inflammatory bowel diseases and juvenile arthritis alongside acute leukemia. Five cohort studies were suitable for more detailed analysis: a rate ratio for leukemia diagnosis after any AI disease was 2.46 (95 % CI 1.17–5.18; heterogeneity I2 15 %) with a random-effects model. Conclusions: The results of this systematic review indicate that AI diseases in childhood are associated with a moderately increased risk of leukemia. The association for individual AI diseases needs further investigation.