Essential thrombocythemia (ET) is a
myeloproliferative disorder characterized by an indolent
clinical course, with a median survival exceeding 20 years. A minority of patients undergo thrombohemorrhagic complications, which might be prevented by cytoreductive treatment in high risk categories.
Alkylating agents (ALK) have been demonstrated to increase the risk of acute
leukemia and
myelodysplastic syndromes in patients with
myeloproliferative disorders, whereas the potential oncogenicity of
hydroxyurea (HU) remains a matter of debate. In this study, we retrospectively investigated long-term development of hematological and non-hematological
second malignancies in 331 patients with ET, analyzing possible associations with
chemotherapy treatments. Median follow-up was 108 months. Of the 194 patients who were treated with
chemotherapy, 116 (60%) received only HU, 38 (19.5%) only ALK (
busulfan or
melphalan) and 40 (20.5%) ALK followed by HU. After a median time of 87 months from the diagnosis of ET, 43 patients developed a
second malignancy, hematological in 15 and non-hematological in 28, for an overall cumulative incidence of 13%. According to the type of treatment,
second malignancies were documented in 11.2% of patients treated with only HU, in 26.3% of patients who received only ALK, and in 25% of those treated with ALK followed by HU. Ten cases (7.3%) were recorded among the 137 patients who did not receive any treatment. Our analysis revealed a significant association between treatment with
alkylating agents and an increased risk of developing second
hematological malignancies, whereas no such association was detected with regard to treatment with
hydroxyurea single agent in our ET population. In addition, different treatment strategies did not affect the risk of developing second solid
cancers.