Acquired immune-related and inflammatory conditions and subsequent chronic lymphocytic leukaemia

Abstract

Immune-mediated pathways have been recognized to be of importance in the pathogenesis of chronic lymphocytic leukaemia (CLL). We assessed a broad variety of immune-related and inflammatory conditions and subsequent CLL development among 4 million adult male veterans admitted to VA hospitals. We identified 3,680 CLL cases with up to 27 years of follow-up. Using Poisson regression analyses restricted to immune-related or inflammatory conditions that occurred more than one year before CLL, we estimated relative risk (RR) and 95% confidence intervals for CLL risk. Elevated CLL risk was found among individuals with prior chronic sinusitis (RR = 1·27, 1·01–1·61). Pneumonia had a borderline (RR = 1·13, 1·00–1·27) association with CLL; the risk was further elevated (RR = 1·35, 1·07–1·72) for latency <5 years. Conversely, chronic non-rheumatic valvular heart disease was associated with 0·76-fold (0·58–0·99) decreased risk. Herpes zoster and simplex were associated with increased (RR = 1·98, 1·40–2·79) and borderline increased (RR = 1·69, 0·96–2·98) CLL risk. There was no general association between autoimmunity and CLL; however, autoimmune haemolytic anaemia was associated with 3·86-fold (1·93–7·74) elevated CLL risk. Individuals with chronic osteoarthritis and prostatitis had 1·14-fold (1·03–1·25) and 1·64-fold (1·14–2·37) elevated CLL risk. These association patterns suggest primary focus on infectious agents rather than autoantigens for future aetiologic CLL studies.