title: Iatrogenic immunosuppression and risk of non-Hodgkin lymphoma in solid organ transplantation: A population-based cohort study in Australia.
abstract: Iatrogenic immunosuppression is a strong risk factor for non-Hodgkin lymphoma (NHL) but the dose-related association between individual immunosuppressive agents and NHL risk is unknown. We conducted a population-based cohort study of 4131 adult Australian liver, heart and lung transplant recipients (1984-2006). We ascertained NHL incidence by probabilistic record linkage between transplant registries and the Australian Cancer Database, and abstracted risk factor data at transplantation and at regular intervals thereafter from medical records. We estimated adjusted hazard ratios (HR) for early (<1 year after transplantation; n = 29) and late (≥1 year; n = 61) NHL using the Fine and Gray proportional subdistribution hazards model that accounted for death as a competing risk. After adjustment for immunosuppression, the risk of both early and late NHL did not significantly differ by organ type. In final models, higher mean daily doses of azathioprine were associated with increased risk of both early [HR 2·20, 95% confidence interval (CI): 1·21-4·01] and late NHL (HR 1·78, 95% CI: 1·12-2·84). There was no association between any other maintenance immunosuppressive agent and NHL risk. This study provides evidence that differences in immunosuppression may explain variation in NHL incidence by organ type, and high doses of azathioprine may independently predict NHL risk.
authors.affiliation: Adult Cancer Program, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Renhua
authors.initials: R
authors.lastname: Na
authors.affiliation: Adult Cancer Program, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia.|Centre for Big Data Research in Health, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Maarit A
authors.initials: MA
authors.lastname: Laaksonen
authors.affiliation: Kirby Institute, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Grulich
authors.affiliation: Adult Cancer Program, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Nicola S
authors.initials: NS
authors.lastname: Meagher
authors.affiliation: The Centenary Research Institute, Australian National Liver Transplant Unit, Royal Prince Alfred Hospital and University of Sydney, Sydney, NSW, Australia.
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: McCaughan
authors.affiliation: St Vincent's Hospital, Sydney, NSW, Australia.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Keogh
authors.affiliation: Adult Cancer Program, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia.|Centre for Big Data Research in Health, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Vajdic
mesh_terms: D000328:Adult; D001315:Australia / Q000453:epidemiology; D001379:Azathioprine / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D007049:Iatrogenic Disease; D007165:Immunosuppression Therapy / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016031:Liver Transplantation; D016040:Lung Transplantation; D008228:Lymphoma, Non-Hodgkin / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects*; D016016:Proportional Hazards Models; D012307:Risk Factors; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D001379:Azathioprine
keywords: cohort; immunosuppression; non-Hodgkin lymphoma; risk; transplantation