Second cancer risk and late mortality in adult Australians receiving allogeneic haematopoietic stem cell transplantation: A population-based cohort study
Vajdic CM, Mayson E, Dodds AJ, O'Brien T, Wilcox L, Nivison-Smith I, Le Marsney R, Daniels B, Ashton LJ; CAST study investigators.
We quantified the risk of second cancer and late mortality in a population-based Australian cohort of 3273 adult (≥15yrs) allogeneic haematopoietic stem cell transplant recipients (1992-2007). Most recipients received non-radiation based conditioning and a peripheral blood graft from a matched, related donor. Using record linkage with death and cancer registries 79 second cancers were identified a median of 3.5 years after transplantation. The competing-risk adjusted cumulative incidence of second cancers was 3.35% (95% CI 2.59-4.24) at 10 years and the cancer risk relative to the matched general population was 2.10 (95% CI 1.65-2.56). We observed an excess risk of melanoma, lip, tongue, oesophagus and soft tissue cancer. Cancer risk relative to the general population was elevated for those transplanted for lymphoma, some leukaemia subtypes and severe aplastic anaemia, recipients who developed chronic graft versus host disease (cGVHD), and irrespective of radiation-based conditioning or stem cell source. In those alive two years after transplantation (n=1463), the cumulative incidence of late mortality was 22.2% (95% CI 19.7-24.9) at 10 years and the risk of death relative to the matched general population was 13.8 (95% CI 12.2-15.6). In multivariable modelling, risk of late death was reduced for females compared to males and those transplanted for chronic myeloid leukaemia compared to acute myeloid leukaemia, and risk was increased for recipients with discordant sex donors, cGVHD, those undergoing second transplants and disease relapse. Adults undergoing allogeneic transplantation have unique cancer and mortality risk profiles that continue to warrant prevention and surveillance activities targeted at high-risk subgroups.