Risk of Secondary Malignancies in Hematopoietic Stem Cell Transplantation Recipients: A Nationwide Population-Based Study in Taiwan

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The improvement of survival after hematopoietic stem cell transplantation has brought about a need to evaluate long-term complications, for instance, secondary malignancies. The risk of subsequent malignancies after hematopoietic stem cell transplantation must be clarified in a large population. To estimate the risk of secondary malignancies in hematopoietic stem cell transplantation survivors and compare it with the risk in patients without hematopoietic stem cell transplantation history. We conducted a population-based retrospective cohort study of 3,059 hematopoietic stem cell transplantation recipients from the National Health Insurance Research Database of Taiwan, containing 1,378 autologous, 1,641 allogeneic, and 40 cord blood stem cell transplantation recipients between 2000 and 2013. A control group of 12,236 patients without an hematopoietic stem cell transplantation history was identified. The covariates included age, sex, comorbidities, stem cell source, facility level of care, and history of total body irradiation. Comorbidities were estimated by the revised Charlson comorbidity index, and a higher score suggested more severe comorbidity. Adjusted hazard ratios were determined by adjusting for age, sex, comorbidity, and facility level of care. Overall, hematopoietic stem cell transplantation recipients had a higher risk of secondary malignancies with an adjusted hazard ratios of 1.348 (p = 0.017). Being male and female (adjusted hazard ratios 1.395, p = 0.009 and adjusted hazard ratios 1.291, p = 0.042, respectively) and pre-hematopoietic stem cell transplantation total body irradiation (adjusted hazard ratios 1.591, p < 0.001) were correlated with a high risk of secondary malignancies. Among the subsequent neoplasms, bone cancer showed the highest risk (adjusted hazard ratios 27.899, p < 0.001), followed by laryngeal (adjusted hazard ratios 6.643, p < 0.001), kidney (adjusted hazard ratios 5.580, p < 0.001), esophageal, pancreatic, thyroid (adjusted hazard ratios 1.993, p < 0.001), and skin (adjusted hazard ratios 1.992, p < 0.001) cancers. The median follow-up duration was 2.16 years in the hematopoietic stem cell transplantation group and 2.57 years in the control group, and the overall median follow-up duration was 2.21 years. Medical practitioners should be aware of the high risk of secondary malignancies in hematopoietic stem cell transplantation recipients later in life. These recipients should be informed about the importance of regular follow-up and photoprotective measures. Lifelong surveillance is recommended.