bl-4162a and Cell-Transformation--Neoplastic

Essential thrombocythemia is a chronic myeloproliferative neoplasm characterized by sustained thrombocytosis, bone marrow megakaryocytic hyperplasia and an increased risk of thrombosis and hemorrhage. The goal of treatment is to prevent the development of vascular complications without increasing the risk of transformation. Patients aged>60 years or a history of thrombosis have a high risk of thrombosis while those with a platelet count>1,500 x 10(9)/l have a higher risk of hemorrhage. Patients with low-risk essential thrombocythemia can be managed appropriately with low-dose of acetylsalicylic acid or even observation only, while patients with a high-risk disease are candidates to receive cytoreductive treatment, hydroxyurea being the first choice therapy. Anagrelide is the most suitable option for patients with resistance or intolerance to hydroxyurea. All patients must be submitted to a rigorous control of cardiovascular risk factors.

Topics: Adult; Age Factors; Aged; Anticoagulants; Aspirin; Cell Transformation, Neoplastic; Disease Progression; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Hydroxyurea; Intraoperative Complications; Janus Kinase 2; Leukemia, Myeloid, Acute; Life Expectancy; Male; Middle Aged; Mutation, Missense; Platelet Aggregation Inhibitors; Point Mutation; Pregnancy; Pregnancy Complications, Hematologic; Primary Myelofibrosis; Quinazolines; Risk Factors; Thrombocythemia, Essential; Thrombophilia

EXELS, a post-marketing observational study, is the largest prospective study of high-risk essential thrombocythemia (ET) patients, with an observation time of 5 years. EXELS found higher event rates of acute leukemia transformation in patients treated with hydroxycarbamide (HC). In the current analysis, we report age-adjusted rates of malignant transformation from 3460 EXELS patients exposed to HC, anagrelide (ANA), or both. At registration, 481 patients had ANA treatment without HC exposure, 2305 had HC without ANA exposure, and 674 had been exposed to both. Standard incidence ratios (SIRs) were calculated using data from the Cancer Incidence in Five Continents database to account for differences in age-, gender-, and country-specific background rates. SIRs for acute myelogenous leukemia (AML) were high in ET patients. SIRs for AML were high in HC-treated patients, but AML was rare in ANA-treated patients; no cases of AML were found in patients only treated with ANA. No statistically significant difference was seen between SIRs for ANA and HC treatment for AML or skin cancer. SIRs for other cancers were similar in the HC and ANA groups and close to 1, indicating little difference in risk. Although statistically inconclusive, this study strengthens concerns regarding possible leukemogenic risk with HC treatment. (NCT00202644).

Topics: Adult; Aged; Aged, 80 and over; Cell Transformation, Neoplastic; Female; Humans; Hydroxyurea; Leukemia, Myeloid, Acute; Male; Middle Aged; Neoplasms, Second Primary; Quinazolines; Thrombocythemia, Essential