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Risk for Secondary Thyroid Carcinoma After Hematopoietic Stem-Cell Transplantation: An EBMT Late Effects Working Party Study

Amnon Cohen, Attilio Rovelli, Domenico Franco Merlo, Maria Teresa van Lint, Edoardo Lanino, Dorine Bresters, Marcello Ceppi, Vittorio Bocchini, André Tichelli, Gerard Socié

From the Department of Pediatrics, University of Genova, Polo del Ponente, San Paolo Hospital, Savona; Bone Marrow Transplantation Unit, Department of Pediatrics, University of Milano-Bicocca, San Gerardo Hospital, Monza; Epidemiology and Biostatistics, Department of Cancer Etiology and Prevention, National Cancer Research Institute; Centro Trapianti di Midollo, San Martino Hospital; Department of Hematology-Oncology, Gaslini Children's Hospital, Genova, Italy; Department of Pediatrics, Leiden University Medical Center, the Netherlands; Division of Hematology, University Hospital, Basel, Switzerland; and the Service d'Hématologie Greffe de Moelle, Hospital Saint Louis, Paris, France

Address reprint requests to Amnon Cohen, MD, Department of Pediatrics, San Paolo Hospital, Via Genova 31, 17100 Savona, Italy; e-mail: a.cohen{at}asl2.liguria.it

Purpose The effects of hematopoietic stem-cell transplantation (HSCT) on thyroid carcinogenesis needs to be determined in a large population. This study evaluates the incidence and the risk factors contributing to secondary thyroid carcinoma (STC) in patients who receive transplantation.

Patients and Methods We performed a retrospective investigational study, comparing data obtained by means of a two-step questionnaire from the 166 centers who replied, and data reported to the European Group for Blood and Marrow Transplantation (EBMT) registry on their transplantation activity. During the follow-up period (1985 to 2003), 32 instances of STC were found within the EBMT cohort of 68,936 patients who received transplants. These patients were then compared with age- and sex-specific incidence rates in the European population and risk factors for STC were analyzed.

Results The standardized incidence ratios (SIRs) of STC in the population who underwent transplantation was 3.26, in comparison with the European population. Multivariate analysis revealed that young age at transplantation was the strongest risk factor for STC (relative risk [RR], 24.61 for age 0 to 10 years; RR, 4.80 for age 11 to 20). Other risk factors were irradiation (RR, 3.44), female sex (RR, 2.79), and chronic graft-versus-host disease (RR, 2.94). Nine patients showed no clinical signs of thyroid illness at diagnosis. Total thyroidectomy and iodine ablation was the standard treatment for the majority of patients, and only one patient died due to STC progression.

Conclusion Long-term survivors of HSCT are at risk for STCs. These results should promote efforts in screening for early detection and treatment guidelines of secondary thyroid cancer after HSCT, especially in patients who receive transplants during childhood and adolescence.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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