Second cancer risk in adults receiving autologous haematopoietic SCT for cancer: a population-based cohort study

Abstract

, CM Vajdic 5 and CAST study group 6 Population-based evidence on second cancer risk following autologous haematopoietic SCT (HCT) is lacking. We quantified second cancer risk for a national, population-based cohort of adult Australians receiving autologous HCT for cancer and notified to the Australasian Bone Marrow Transplant Recipient Registry 1992Registry -2007. Cancer diagnoses and deaths were ascertained by linkage with the Australian Cancer Database and National Death Index. Standardized incidence ratios (SIRs) were calculated and Cox regression models were used to estimate within-cohort risk factors treating death as a competing risk. During a median 2.5 years follow-up, second cancer risk was modestly increased compared with the general population (SIR 1.4, 95% confidence interval 1.2-1.6); significantly elevated risk was also observed for AML/myelodysplastic syndrome (SIR ¼ 20.6), melanoma (SIR ¼ 2.6) and non-Hodgkin lymphoma (SIR ¼ 3.3). Recipients at elevated risk of any second cancer included males, and those transplanted at a younger age, in an earlier HCT era, or for lymphoma or testicular cancer. Male sex, older age (445 years) and history of relapse after HCT predicted melanoma risk. Transplantation for Hodgkin lymphoma and older age were associated with lung cancer risk. Second malignancies are an important late effect and these results inform and emphasize the need for cancer surveillance in autologous HCT survivors.Bone Marrow Transplantation (2014) 49, 691-698; doi:10.1038/bmt.2014.13; published online 17 February 2014Keywords: autologous transplantation; outcomes; risk; surveillance INTRODUCTION Autologous haematopoietic SCT (HCT) is increasingly being used in Australia and elsewhere as a therapy for several haematopoietic and solid organ malignancies. 1,2 Life expectancy following HCT has also improved, 3 increasing the number of HCT survivors globally. Characterizing late effects and identifying those at risk will maximize the long-term health of HCT recipients.Second cancers are a recognized late effect of chemo-radiation therapy in general, and in the HCT setting specifically. 4-11 The cumulative incidence of second cancer after autologous HCT may be as high as 29% after 15 years, 11 with the greatest excess risk observed for AML and myelodysplastic syndromes (MDSs). 10,[12][13][14][15] Most prior studies have examined second cancer risk in recipients of allogeneic and autologous HCT, with the largest based on international transplant registry cohorts. 9 Furthermore, most studies ascertained second cancers from hospital records or by self-report, potentially under-estimating risk. There are no population-based estimates of the risk of secondary cancer in adult recipients of autologous HCT. We examined the incidence and risk factors for second cancer in a national, population-based cohort of 7765 adult Australian autologous HCT recipients, 1992HCT recipients, -2007

Skin Cancer Risk in Hematopoietic Stem-Cell Transplant Recipients Compared With Background Population and Renal Transplant Recipients

“…While this Australian study reported excess risk for MM after autologous HSCT, 14 we observed no evidence of increased MM risk in our cohort. In the Australian study, however, TBI was part of the conditioning regimen for some of the autologous HSCT recipients, with patients undergoing the TBIbased regimen less frequently in recent years.…”

Secondary solid cancer screening following hematopoietic cell transplantation

“…A report restricted to autologous HCT demonstrated a SIR of 2.55 for melanoma, and multivariate analysis revealed age ⩾ 45 years, male patients and relapse following HCT as risk factors for melanoma development. 19 …”

Late effects of blood and marrow transplantation

“…The cumulative incidence is 1%–6% at ten years after HCT, and continues to rise over time without a plateau. 139–142 The most common sites include oral cavity, skin, breast and thyroid, but rates are also elevated in esophagus, liver, nervous system, bone and connective tissues compared with the general population. 143 Myeloablative TBI, young age at HCT, chronic GvHD and prolonged immunosuppressive medications beyond two years are well-documented risk factors for many types of cancers.…”