The risk of major bleeding during induction chemotherapy in adolescents and adults with acute myeloid leukemia (except acute promyelocytic leukemia, which we did not study) was similar with platelet-transfusion thresholds of 20,000 per cubic millimeter and 10,000 per cubic millimeter (or 10,000 to 20,000 per cubic millimeter when body temperature exceeded 38 degrees C, there was active bleeding, or invasive procedures were needed). Use of the lower threshold reduced platelet use by 21.5 percent.

JAK2 617V>F mutation occurs in a homozygous state in 25% to 30% of patients with polycythemia vera (PV) and 2% to 4% with essential thrombocythemia (ET IntroductionPatients with Philadelphia-negative chronic myeloproliferative disorders (CMPDs) 1 harbor a recurrent mutation in the Janus tyrosine kinase 2 (JAK2) gene, consisting of a valine-tophenylalanine change at position 617 (JAK2 617VϾF) in the JH2 pseudo-kinase domain. [2][3][4][5] The JAK2 617VϾF mutation is present in the vast majority of patients with polycythemia vera (PV) 2-5 and in 40% to 60% of those with essential thrombocythemia (ET) 6-8 or myelofibrosis with myeloid metaplasia (MMM). 9,10 JAK2 617VϾF can also occasionally be detected in "atypical" MPD, myelodysplastic syndromes, chronic myelomonocytic leukemia, systemic mastocytosis, chronic neutrophilic leukemia, and eosinophilic disorders. 11-13 Mutant JAK2 is a constitutively active tyrosine kinase that confers growth factor independence in transfected hematopoietic cell lines [2][3][4][5] and is at the basis of the phenomenon of erythropoietin-independent erythroid colony (EEC) growth that is a hallmark of most PV patients and is also less frequently reported in patients with ET. 14 A key role for the "gain-of-function" 15 of mutated JAK2 in the pathogenesis of CMPD is supported by in vitro studies, which showed enhanced JAK-STAT signaling in cells bearing the mutant allele, and by in vivo animal models in which erythrocytosis 3,16 and eventually myelofibrosis 16,17 developed following transplantation of hematopoietic cells transfected with mutant JAK2 into mice.About 25% to 30% of PV and MMM patients, and 2% to 4% of ET patients, harbor the mutation in the homozygous state, a condition where at least 51% of JAK2 alleles in granulocytes are mutated as the result of a mitotic recombination process. 2-5 While a consistent number of reports have investigated the impact of the presence of 617VϾF mutation per se on the clinical and hematologic profile of CMPD patients, a few studies have specifically addressed the consequences of JAK2 617VϾF mutation when harbored in the homozygous state. 18 The complete loss of normal JAK2 allele is expected to have profound effects on cell phenotype. As a matter of fact, in cotransfection experiments, the wild-type

No abstract

BackgroundPrior thrombosis is a well-established risk factor for re-thrombosis in polycythemia vera and essential thrombocythemia but scarce data are available on the rate of re-thrombosis and the optimal strategy for prevention of recurrence.

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In idiopathic thrombocytopenic purpura (ITP), corticosteroids have been widely recognized as the most appropriate firstline treatment, even if the best therapeutic approach is still a matter of debate. Recently, a single high-dose dexamethasone (HD-DXM) course was administered as first-line therapy in adult patients with ITP. In this paper we show the results of 2 prospective pilot studies (monocentric and multicentric, respectively) concerning the use of repeated pulses of HD-DXM in untreated ITP patients. In the monocenter study, 37 patients with severe ITP, age at least 20 years and no more than 65 years, were enrolled. HD-DXM was given in 4-day pulses every 28 days, for 6 cycles. Response rate was 89.2%; relapse-free survival (RFS) was 90% at 15 months; long-term responses, lasting for a median time of 26 months (range 6-77 months) were 25 of 37 (67.6%). In the multicenter study, 95 patients with severe ITP, age at least 2 years and no more than 70 years, were enrolled. HD-DXM was given in 4-day pulses every 14 days, for 4 cycles; 90 patients completed 4 cycles. Response rate (85.6%) was similar in patients classified by age (< 18 years, 36 of 42 ‫؍‬ 85.7%; > 18 years, 41 of 48 ‫؍‬ 85.4%, P ‫؍‬ not significant), with a statistically significant difference between the second and third cycle (75.8% vs 89%, P ‫؍‬ .018). RFS at 15 months 81%; long-term responses, lasting for a median time of 8 months (range 4-24 months) were 67 of 90 (74.4%). In both studies, therapy was well tolerated. A schedule of 3 cycles of HD-DXM pulses will be compared with standard prednisone therapy (eg, 1 mg/kg per day) in the next randomized Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) trial. (Blood.

The prognostic value of 12 clinical and haematological parameters, recorded at diagnosis, in myelofibrosis with myeloid metaplasia (MMM) was retrospectively analysed in a consecutive series of 133 patients followed for a minimum of 60 months. Multivariate analysis showed that the following features were associated with a significantly shorter survival: (1) short period of time (less than 13 months) between first symptoms and diagnosis; (2) anaemia (haemoglobin less than 10 g/dl); (3) leucocyte count greater than 12 x 10(9)/l; (4) peripheral blood granulocyte precursors greater than 10%. Age, splenectomy and percentage of peripheral blood metamyelocytes were found significantly to affect survival only from univariate analysis, whereas sex, size of spleen, thrombocytopenia and thrombocytosis were of no prognostic significance. These data suggest that a more intensive chemotherapy might be useful for younger patients with bad prognostic factors at diagnosis.

A multicenter retrospective analysis was performed to estimate the frequency of thrombosis and hemorrhage after surgical procedures in patients with polycythemia vera (PV) and patients with essential thrombocythemia (ET