Second malignancies in essential thrombocythemia (ET): a retrospective analysis of 331 patients with long-term follow-up from a single institution

Abstract

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.

Risk of second primary malignancies in a population-based study of adult patients with essential thrombocythemia

“…[13] . Another retrospective study from Italy (n = 331) showed cumulative incidence of SPM of 13% from the time of diagnosis of ET [17] . The study determined a particularly higher incidence of AML [17] .…”

“…Another retrospective study from Italy (n = 331) showed cumulative incidence of SPM of 13% from the time of diagnosis of ET [17] . The study determined a particularly higher incidence of AML [17] . The risk of developing AML in ET depends on multiple factors such as old age, decreased hemoglobin and increased platelet count ≥ 1000 × 10 9 /L [28] .…”

“…A study from Italy has demonstrated that the use of alkylating agents such as melphalan may be associated with a higher risk of developing second hematologic malignancies but not nonhematological malignancies [17] . Prior studies assessing the risk of SPM in ET utilized data mainly from outside the Unites States.…”

Chronic myeloproliferative neoplasms and subsequent cancer risk: a Danish population-based cohort study

“…14 Drugs previously used widely for the treatment of CMPNs (eg, busulfan, P32, and chlorambucil) have well-established carcinogenic potential, [15][16][17] especially when used in combination or sequentially. 18,19 Because the increased incidence and risk of AML among CMPN patients treated with these drugs has been recognized, their use has declined. In the past several years, the most widely prescribed drug to treat patients with CMPNs has been hydroxyurea (HU).…”

“…The risk of leukemia attributed to HU when used as a single cytotoxic drug treatment for CMPN is under discussion, because studies conducted thus far have been unable to distinguish the leukemogenic effects of the CMPN disease from those of the treatment. 15,17,18 Previously, the incidence of solid tumors among CMPN patients compared with the general population was examined according to specific treatment. In a secondary analysis of a randomized controlled trial, 461 PV patients 65 years of age or more were initially treated with P32.…”