From Smoke to Smother: Secondary Sarcoma following Stem Cell Transplantation for Thalassemia

Introduction

Secondary malignant neoplasms (SMN) are major sequelae following cancer treatment during childhood and adolescence. Their cumulative incidence rate reaches 7.9% after 30 years (Friedman et al., J Natl Cancer Inst 2010; 1083–1095), and thereby SMN represent the leading cause of non-relapse late mortality. Risk factors for SMN following haematopoietic stem cell transplantation (HSCT) are the duration of chemotherapy prior to HSCT, total body irradiation and young age. In general, secondary haematological malignancies are related to chemotherapy, whereas most secondary solid malignancies are suspected as radiotherapy-induced (Rizzo et al., Blood 2009; 1175–1183). Accordingly, sequence following HSCT may include both subsequent haematological as well as solid malignancies, especially in case of radiation during conditioning regimen. Whereas secondary haematological malignancies usually present within few years from HSCT, secondary solid malignant neoplasms occur later without reaching a plateau, hence, their incidence increases even 20 years from HSCT (Baker et al., J Clin Oncol 2003; 1352–1358).

Whereas treatment related malignancies may be acceptable complications from therapy of an otherwise deadly cancer, such side effects are even more fateful in the treatment of a non-malignant disease like thalassemia. On the other hand, due to the overall low complication rate there is an increasing number of HSCT for haemoglobinopathies in paediatric patients. In this regard, reduced intensity regimen and waiving radiation from conditioning for HSCT in these disorders may not only reduce early toxicity but also minimize the risk of SMN. Nevertheless, few patients have experienced malignancies subsequent to HSCT for haemoglobinopathies, but due to the rarity of cases, the true incidence of treatment induced malignancies in these patients is yet to be elucidated.

Herein, we report the first case of a subsequent undifferentiated soft tissue sarcoma (USTS) in a 9-year-old boy 4 years from matched-sibling donor HSCT for thalassemia. Although an incidental coincidence cannot be excluded, physicians should be aware of a possible association.