bl-4162a and Anemia

Median survival of patients with myelofibrosis with myeloid metaplasia (MMM) ranges from 3.5 to 5 years, but there is a wide variability. The degree of anemia (Hb < 10 g/dL) is the most important prognostic factor, followed by constitutional symptoms and abnormal karyotype. In recent years, different prognostic scoring systems for MMM have been proposed. In some of them three prognostic groups (low, intermediate, and high risk) are recognized, while others recognize a high and a low-risk group only. Median survival of the low-risk group ranges from seven to nine years, while the minority of high-risk patients survive for a median of less than two years. Younger patients with MMM survive longer (median survival above ten years). Among the latter patients, based on Hb value, constitutional symptoms, and blood blast-cell percentage, two prognostic groups can also be identified, with median survival of less than three years and almost 15 years, respectively. Conventional treatment of MMM is mostly palliative and based on cytolytic treatment (usually hydroxyurea), androgen therapy and splenectomy in selected patients. Allogeneic hemopoietic transplant is a therapeutic possibility with the potential for cure in younger patients with bad prognostic features. The role in MMM of newer treatment strategies such as autologous transplantation or the administration of anti-angiogenic drugs such as thalidomide is currently being evaluated.

Topics: Aged; Anemia; Aneuploidy; Angiogenesis Inhibitors; Bone Marrow Transplantation; Case Management; Combined Modality Therapy; Female; Hemoglobins; Humans; Hydroxyurea; Karyotyping; Male; Middle Aged; Palliative Care; Primary Myelofibrosis; Prognosis; Quinazolines; Risk; Severity of Illness Index; Splenectomy; Survival Analysis; Thalidomide

In this retrospective multi-centre study, we report our experience with anagrelide in the treatment of thrombocytosis in patients with chronic myeloproliferative diseases. Our study included 52 patients (age 20-78 years). The initial anagrelide dose was, in general, 0.5 mg once daily and mean maintenance dosage was 1.7 mg/day. The overall response rate was 79% including 75% complete remission and 4% partial remission. Forty-two patients (81%) had adverse effects and in 29% of the study population, the adverse effects necessitated cessation of anagrelide. The most common adverse effect was moderate anaemia (50%). Two patients experienced erectile dysfunction which has been described only once previously in association with anagrelide treatment. One patient progressed to acute leukaemia. However, this patient had been pre-treated with two potentially leukaemogenic drugs and had only been in short-term treatment with anagrelide. Furthermore, a total of 13 events were recorded. More than 25% of these events occurred in patients with platelet counts between 400 and 600 x 10(9)/l and almost 40% of all events occurred in patients with platelet counts above 400 x 10(9)/l. This observation supports the hypothesis that aggressive control of thrombocytosis to a platelet count <400 x 10(9)/l might reduce the number of thrombohaemorrhagic events. Anagrelide is safe and effective in reducing the platelet counts, but a high proportion of the patients discontinue treatment because of the adverse effects of the drug.

Topics: Adult; Aged; Anemia; Chronic Disease; Female; Hemorrhage; Humans; Male; Middle Aged; Myeloproliferative Disorders; Platelet Aggregation Inhibitors; Quinazolines; Retrospective Studies; Thrombocytosis; Thromboembolism; Treatment Outcome

Anagrelide is a drug effective in reducing platelet counts in essential thrombocythemia (ET) and Ph1-negative myeloproliferative neoplasms. The aim of this study was to evaluate the real-life use of anagrelide in patients with ET followed over 25 years at the Haematological Institutes belonging to "Ph1-negative Myeloproliferative Neoplasms Latium Group.". Eligibility criteria were diagnosis of ET and treatment with anagrelide. Data were collected through an ad hoc case report form.. One hundred and fifty patients received anagrelide for a median time of 7.4 years (0.1-23.2). Anagrelide was administered as first-line therapy in 34.7% of patients, as second-line in 52% and as third-line in 13.3%: 85.4% responded to therapy. Sixty-eight/136 evaluable patients reported side effects: palpitations, peripheral vasodilation, anaemia, diarrhoea and gastric distress. Fourteen thrombotic (arterial 10, venous 4) and 51 bleeding events (minor 48, major 3) occurred. Sixteen/150 (10.6%) patients developed secondary myelofibrosis and 3/150 (2%) an acute myeloid leukaemia.. In our experience, anagrelide is an effective drug in reducing platelet levels in a high percentage of patients with ET. It is especially addressed to younger people. A careful assessment of the thrombotic risk and monitoring of cardiac function, at diagnosis and during follow-up, is mandatory.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anemia; Disease Management; Disease Susceptibility; Drug Substitution; Female; Follow-Up Studies; Health Care Surveys; Humans; Italy; Male; Middle Aged; Pregnancy; Pregnancy Complications, Hematologic; Prognosis; Quinazolines; Retreatment; Retrospective Studies; Thrombocythemia, Essential; Thrombosis; Treatment Outcome; Young Adult

Anagrelide represents a treatment option for essential thrombocythemia, although its place in therapy remains controversial.. To assess the impact of mutational status in response rates and development of adverse events during long-term use of anagrelide.. We retrospectively evaluated 67 patients with essential thrombocythemia treated with anagrelide during 68 (4-176) months.. Mutational frequencies were 46.3%, 28.3%, and 1.5% for JAK2V617F, CALR and MPL mutations. Anagrelide yielded a high rate of hematologic responses, which were complete in 49.25% and partial in 46.25%, without differences among molecular subsets. The rate of thrombosis during treatment was one per 100 patient-years, without excess bleeding. Anemia was the major adverse event, 30.3% at 5-yr follow-up, being more frequent in CALR(+) (P < 0.05). Myelofibrotic transformation developed in 14.9% (12.9%, 21%, and 12.5% in JAK2V617F(+), CALR(+), and triple-negative patients, respectively, P = NS) and those treated >60 months were at higher risk, OR (95% CI) 9.32 (1.1-78.5), P < 0.01, indicating the need for bone marrow monitoring during prolonged treatment.. Although CALR(+) patients were at higher risk of developing anemia, anagrelide proved effective among all molecular subsets, indicating that mutational status does not seem to represent a major determinant of choice of cytoreductive treatment among essential thrombocythemia therapies.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Calreticulin; Child; Female; Follow-Up Studies; Gene Expression; Humans; Janus Kinase 2; Male; Middle Aged; Mutation; Platelet Aggregation Inhibitors; Primary Myelofibrosis; Quinazolines; Receptors, Thrombopoietin; Retrospective Studies; Thrombocythemia, Essential

Essential thrombocythemia (ET) can be complicated by life-threatening thrombosis and has a risk of converting into acute leukemia. Cytoreductive therapy may reduce the risk of thromboembolic complications. Herein, we report the results of a long-term study of patients with ET treated with anagrelide to control thrombocytosis.. Thirty-nine (34 evaluable) patients (median age, 33 years; 24 previously untreated) were enrolled between 1989-1996; the mean platelet count prior to therapy was 1197x10(9)/L. Only 9 out of 34 evaluable patients were at high risk of thrombosis (platelet count more than 1500x10(9)/L). The initial dose of anagrelide (0.5 mg/bid for 7 days) was increased by 0.5 mg/day (maximum dose: 3 mg/day) until a response was seen.. A complete response (platelets < 450x10(9)/L for >1 month) was seen in 15 /34 (44%) patients and a partial response (platelets 450-600x10(9)/L for >1 month) was seen in 17/34 ( 50%), so that the some kind of response was seen in 32/34 (94%) of the patients at a median time of 4.2 months after starting treatment. Seventeen patients (50%) are still being treated and have achieved platelet control for a maximum follow-up of 12.5 years. Late onset anemia occurred in 4/39 patients. Three out of 39 patients (8%) had cardiac disorders.. Anagrelide appears suitable for controlling thrombocytosis in ET patients over the long-term. This drug may be used in patients younger than 60 years, with the exclusion of women of child-bearing potential and subjects aged 40-60 years with a history of major thrombotic events. Anagrelide should not be administered to patients with cardiac disorders, and a careful approach to patients should include monitoring of heart function before and during treatment.

Topics: Adult; Anemia; Female; Hemoglobins; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Quinazolines; Stomach Diseases; Tachycardia; Thrombocythemia, Essential; Time Factors

Topics: Adolescent; Adult; Anemia; Cohort Studies; Follow-Up Studies; Hemorrhage; Humans; Hydroxyurea; Incidence; Middle Aged; Quinazolines; Risk; Thrombocythemia, Essential; Thrombophilia; Thrombosis