Patients with Polycythemia Vera and Essential Thrombocytosis Have a Higher Risk of Prior or Concurrent Tumors Compared to Patients with Secondary Thrombocytosis

Polycythemia vera (PV) and Essential thrombocytosis (ET) are chronic myeloproliferative neoplasms (MPNs) that arise from aberrant, clonal hematopoietic stem cells. MPNs are associated with an elevated risk of arterial and venous thrombosis as well as with transformation to myelofibrosis (MF) and acute myeloid leukemia (AML). Diseases causing secondary, or reactive, elevation of the red cell or platelet counts are not considered clonal and do not predispose to the development of hematologic malignancies. Prior reports in patients of European descent suggest as many as 15% of patients with MPNs die of unrelated malignancies, but there is no data suggesting that these malignancies precede the MPN diagnosis. In a large, ethnically diverse population, we investigated whether tumors other than MF or AML (“unrelated tumors”) occurred more commonly among patients with ET and PV than among patients with secondary thrombocytosis.

We performed a retrospective chart review of all consecutive patients diagnosed with ET, PV or secondary thrombocytosis (ST) between April, 1992 and June, 2010. Laboratory data and the World Health Organization criteria were utilized to distinguish ET, PV and ST. In addition to demographic and MPN-specific diagnostic data and complication rates, we recorded the prior or concurrent, pathologically-confirmed diagnosis of unrelated tumors, their histology and treatment received. We performed a multivariate, exact logistic regression analysis adjusted for age at diagnosis of MPN, sex, ethnicity, JAK2 mutational status and MPN subtype to determine whether MPN patients are more likely to have had unrelated tumors than ST patients.

Seventy-six patients with MPNs, 55 with ET and 21 with PV, were compared to 82 patients with ST. The median age at diagnosis in the MPN group was 53.5 years (range 19 –84); it was 46 years in the ST group (range 16 – 87). The majority (57.9%) of the patients with MPNs were Hispanic whites, 21% were Asian, 15.8% were non-Hispanic whites, and 5.3% were Black. Of the 82 patients with ST, 73.2% were Hispanic whites, 9.8% were Asian, 9.8% were Black and 4.9% were non-Hispanic whites. Thrombosis occurred in 12 (15.8%) of the MPN patients and in none of the ST patients. We observed a statistically significantly higher incidence of unrelated tumors in MPN patients (17.1%) as compared to ST patients (1.2%). The multivariate analysis revealed an odds ratio for unrelated tumors among MPN patients of 5.19 (95% CI 1.04 – 22.1, p = 0.038) compared to ST patients. Of the 13 unrelated tumors which were diagnosed among patients with MPN, 11 were diagnosed prior to the MPN diagnosis and included 5 breast cancers (2 treated surgically, 2 treated with surgery, radiation and chemotherapy, 1 treated with surgery and radiation only); 3 neural tumors including 1 meningioma, 1 pituitary macroadenoma, and 1 schwannoma (all treated with surgery alone); 2 hematologic malignancies including a low grade B-cell lymphoma and a rectal MALT lymphoma (1 treated with combination chemotherapy and 1 treated with Rituxan alone); and 1 prostate cancer (treated with hormonal therapy alone). Two patients developed unrelated tumors during the course of their MPN; these included 1 patient with gastrointestinal stromal tumor and 1 with multiple myeloma. Interestingly, the latter patient has maintained a normal platelet count without cytoreductive ET therapy for the 18 months since autologous transplant for his myeloma.

Patients with PV and ET have a significantly higher risk of having prior or concurrent tumors unrelated to progression of their MPN when compared to patients with ST.

No relevant conflicts of interest to declare.