Pre-fibrotic/early primary myelofibrosis vs. WHO-defined essential thrombocythemia: The impact of minor clinical diagnostic criteria on the outcome of the disease.

The 2016 revised WHO criteria for the diagnosis of pre-fibrotic/early primary myelofibrosis (pre-PMF) require at least one of the following four borderline expressed minor clinical criteria: anemia, leukocytosis, elevated lactate dehydrogenase and splenomegaly. In this study, we evaluated the relative frequency of these four criteria in a group of 170 pre-PMF patients and compared them to 225 ET cases. More than 91% of pre-PMF cases showed one or more of these features required for diagnosis, by contrast with only 48% of ET patients. According to clinical data the cumulative risk of progression to advanced/overt PMF in pre-PMF was 36.9% after 15 years. After fitting cox regression models to analyze the impact of the minor criteria on overall survival, only leukocytosis remained as a significant predictor of survival in both pre-PMF and ET. Molecular characterization showed differences in survival in pre-PMF but not ET, with CALR being a more favorable mutation than JAK2. The different outcome of pre-PMF versus ET and associated molecular genetic data supports the concept of two different entities, rather than a continuum of the same disease. Although slightly less than 50% of ET patients also show one or more minor clinical criteria, accurate distinction between ET and pre-PMF is possible by following an integrated approach including histomorphological diagnosis and presence of minor clinical criteria.

Experience with lenalidomide in an Austrian non-study population with advanced myelofibrosis.

Current literature provides conflicting evidence regarding the efficacy of lenalidomide in patients with myelofibrosis (MF). The aim of this work was to evaluate the efficacy of lenalidomide in patients with MF treated within a named patient program in Austria. A total of 22 patients with MF were treated with lenalidomide in 7 different centres throughout Austria. Median age of patients was 68 years. Primary MF was present in 13 patients. Eight patients had post-polycythemia vera (post-PV) and 1 post-essential thrombocythemia (post-ET) MF. According to the Dynamic International Prognostic Scoring System (DIPSS), all patients were scored within the intermediate-2 or high-risk group. Approximately one-third of patients were treated with 2 or more prior therapies. The overall response rate according to International Working Group (IWG) criteria was 12.5 %. Efficacy of lenalidomide was moderate in this non-study patient population. Limiting factors seemed to be stage of disease and risk profile of patients included in this analysis.

Extensive pleural and pericardial effusion in chronic myeloid leukemia during treatment with dasatinib at 100 mg or 50 mg daily.

Dasatinib is considered an effective drug in imatinib-resistant chronic myeloid leukemia. Although reported to be well-tolerated, severe events such as pleural or pericardial effusion have been reported at 140 mg daily. We examined our chronic myeloid leukemia patients treated with dasatinib at 100 mg or 50 mg daily and identified 4 of 13 patients who developed marked effusion formation. In 2 patients, grade III/IV pleural and/or pericardial effusions were recorded. All 4 patients had received previous anti-leukemia therapy but none had pre-existing cardiac or pulmonary diseases. In 3 patients, dasatinib had to be discontinued despite treatment with diuretics and glucocorticosteroids. In conclusion, dasatinib-treated chronic myeloid leukemia patients are at risk for the development of pleural and pericardial effusions even when the drug is administered at 100 mg or 50 mg daily. Therefore, all patients should be examined for pre-existing comorbidity and risk factors before starting dasatinib and all should have repeated chest X-rays during long-term dasatinib therapy.

First annual report of the Austrian CML registry.

The Austrian chronic myeloid leukemia (CML) registry monitors individual disease courses, treatments applied, clinical outcome, and side effects of CML patients on a nationwide basis to provide data on the "real-life" situation and to complement the information and interpretation gained from the selected patient population observed in clinical trials. This report summarizes the Austrian CML registry data as of March 2009. A total of 179 patients have been registered with a median number of 1012 follow-up visits and median observation duration of 20 months. At diagnosis most patients (n = 163) were in chronic phase (early, late, and secondary), whereas only 4 were in advanced phase. A total of 137 patients were treated with tyrosine kinase inhibitors (TKIs), of which 14 received first and second generation TKIs sequentially. Other treatment modalities included chemotherapy or interferon and stem cell transplantation (SCT). Cumulative incidence rates for complete hematological responses (CHR) were 91.6% and 94.4% at 12 and 24 months, respectively, compared to cumulative incidence rates of complete cytogenetical response rates of 64% and 80% at these timepoints. A total of 5 patients progressed from chronic phase to accelerated (n = 3) and blastic phase (n = 2) while receiving imatinib standard dose. Estimated overall survival (OS) rate at 60 months was 90% and progression free survival (PFS) according to European Leukemia Net (ELN) failure definition was 58%.

Anagrelide for thrombocytosis in myeloproliferative disorders: a prospective study to assess efficacy and adverse event profile.

BACKGROUND: Although the platelet count does not correlate with the rate of thrombosis, there is evidence that a strict control of the platelet count decreases the incidence of thromboembolic complications in essential thrombocythemia. In the current study, the authors evaluated the efficacy and tolerability of anagrelide in thrombocytosis associated with myeloproliferative disorders. METHODS: The study cohort comprised 97 patients (n = 69 females, n = 28 males) with a median age of 59 years (range, 21-80 years). Patients with essential thrombocythemia (n = 79) or with thrombocytosis due to polycythemia vera (n = 16) or to chronic idiopathic myelofibrosis (n = 2) were enrolled in the multicenter, prospective study. Patients received anagrelide at a starting dose of 0.5 mg twice per day, which was then adjusted for each patient. RESULTS: Treatment with anagrelide resulted in a rapid decrease in the platelet count, from a median baseline platelet count of 743 x 10(9)/L to a median platelet count of 441 x 10(9)/L after 6 months (P < 0.0001). The proportion of patients with a platelet count < 600 x 10(9)/L increased from 30% at baseline to 77% after the 6-month study period. The rate of major thrombotic complications significantly decreased from 5% to 2% (P = 0.2568). For patients with essential thrombocythemia, the reduction of major thromboembolic complications was significant (P = 0.0455). The rate of minor thromboembolic complications decreased from 25% before anagrelide treatment to 14% during anagrelide treatment (P = 0.0278). No severe side effects were observed during the study period. There was, however, evidence that concomitant administration of acetylsalicylic acid may increase bleeding tendency. CONCLUSIONS: Anagrelide was an effective and well tolerated treatment modality for reducing platelet counts in both newly diagnosed and pretreated patients with thrombocytosis due to myeloproliferative disorders.