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Increasing indications for transplant and improvements in early transplant outcomes have lead to an increasing population of cancer survivors. Much of our knowledge regarding late effects comes from studies in adult recipients or hospital based studies where duration or reliability of follow-up data is limited. The aim of our study was to examine the risk of second malignancy and late mortality in a population-based cohort of pediatric recipients of allogeneic hematopoietic stem cell transplant (HSCT) in Australia.
Methods:
Australian pediatric allogeneic HSCT recipients aged less than 15 years and treated for a hematological malignancy from 1982-2007, were identified from pediatric hospitals and the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR). Patient records were linked to records held by the Australian Cancer Database (ACD) and National Death Index to determine second cancers and deaths in the cohort. Standardized rates (SIRs & SMRs) and risk factors were characterised for second malignancies following HSCT and late deaths (deaths occurring 2 or more years after HSCT).
Results:
Second cancers were observed in 17 of the 674 (2.5%) HSCT recipients with a primary cancer diagnosis recorded on the ACD. Thyroid cancer was the most common second cancer observed (n=8) followed by brain tumours (n=4). The rate of second cancers occurring after HSCT was 20 times higher than expected based on rates in the age-, sex- and calendar-year matched general population (SIR=20.33, 95%CI= 12.64-32).Total body irradiation was associated with a 4-fold increased risk of secondary malignancy, while non-Hodgkin lymphoma patients were 7 times more likely to develop a second malignancy compared to acute lymphoblastic leukaemia patients.
While the overall rate of late death was 36 times greater than the rate seen in the age-, sex- and calendar-year matched general population (SMR=35.93, 95%CI=26.74-48.29), rates of death returned to levels similar to the general population 10 years after HSCT.
Conclusions:
This is the first study to use population-based registry data to determine the risk of second cancer and late death in pediatric patients with a hematologic cancer treated by allogeneic HSCT. The increased risk of second cancer and late deaths in this population highlights the importance of long-term follow up, surveillance and early detection of second cancer.