Search results for "Myelofibrosis"
showing 10 items of 60 documents
Die Entwicklung der Myelofibrose bei der "präfibrotischen"cIMF
2002
Zusammenfassung Wegen des erst kurzlich mit Erscheinen der neuen WHO-Klassifikation der chronischen myeloproliferativen Erkrankungen (CMPE) aufgegebenen Festhaltens an einer Knochenmarksfibrose als wesentliches Merkmal der chronischen idiopathischen Myelofibrose (cIMF) sind Verlaufsuntersuchungen zu der Entwicklung einer Myelofibrose (MF) bei dieser Entitat nur von fibrotischen Stadien mit widerspruchlichen Ergebnissen bekannt. Deshalb wurde eine retrospektive Studie an Verlaufsbiopsien von 38 Patienten mit cIMF ohne initiale Fibrose mit der Frage nach der Haufigkeit, der Geschwindigkeit sowie dem Ausmas der Entwicklung einer MF durchgefuhrt. Unabhangig von einer Chemotherapie fanden wir ei…
Circulating interleukin (IL)-8, IL-2R, IL-12, and IL-15 levels are independently prognostic in primary myelofibrosis: a comprehensive cytokine profil…
2011
Purpose Abnormal cytokine expression accompanies myelofibrosis and might be a therapeutic target for Janus-associated kinase (JAK) inhibitor drugs. This study describes the spectrum of plasma cytokine abnormalities in primary myelofibrosis (PMF) and examines their phenotypic correlates and prognostic significance. Patients and Methods Patients included in this study were required to have archived plasma, bone marrow biopsy, and cytogenetic information available at the time of first referral to the Mayo Clinic. Multiplex biometric sandwich immunoassay was used to measure plasma levels of 30 cytokines. Results In total, 127 PMF patients were studied; comparison with normal controls (n = 35) r…
Presence of calreticulin mutations in JAK2-negative polycythemia vera
2014
Abstract Calreticulin (CALR) mutations have recently been reported in JAK2- and MPL-negative Myeloproliferative Neoplasms (MPN), particularly essential thrombocythemia (ET) and primary myelofibrosis (PMF).The clinical course of sporadic CALR-mutated patients seems to be more indolent than that of JAK2-mutated patients. In contrast, no CALR mutation has been found in the 647 published cases of Polycythemia Vera (PV) patients tested. Consequently, CALR mutations were considered exclusive to JAK2 and MPL mutations. Since 98% of PV patients harbor a JAK2 mutation (mostly the V617F mutation in exon 14 and more rarely, in exon 12), the absence of CALR mutations in PV seemed logical. Here, we desc…
Cardiovascular events and intensity of treatment in polycythemia vera.
2013
A b s t r ac t Background Current treatment recommendations for patients with polycythemia vera call for maintaining a hematocrit of less than 45%, but this therapeutic strategy has not been tested in a randomized clinical trial. Methods We randomly assigned 365 adults with JAK2-positive polycythemia vera who were being treated with phlebotomy, hydroxyurea, or both to receive either more intensive treatment (target hematocrit, <45%) (low-hematocrit group) or less intensive treatment (target hematocrit, 45 to 50%) (high-hematocrit group). The primary composite end point was the time until death from cardiovascular causes or major thrombotic events. The secondary end points were cardiovascula…
SNPs array karyotyping reveals a novel recurrent 20p13 amplification in primary myelofibrosis.
2011
The molecular pathogenesis of primary mielofibrosis (PMF) is still largely unknown. Recently, single-nucleotide polymorphism arrays (SNP-A) allowed for genome-wide profiling of copy-number alterations and acquired uniparental disomy (aUPD) at high-resolution. In this study we analyzed 20 PMF patients using the Genome-Wide Human SNP Array 6.0 in order to identify novel recurrent genomic abnormalities. We observed a complex karyotype in all cases, detecting all the previously reported lesions (del(5q), del(20q), del(13q), +8, aUPD at 9p24 and abnormalities on chromosome 1). In addition, we identified several novel cryptic lesions. In particular, we found a recurrent alteration involving cytob…
Phase ia/ii, two-arm, open-label, dose-escalation study of oral panobinostat administered via two dosing schedules in patients with advanced hematolo…
2013
Panobinostat is a potent oral pandeacetylase inhibitor that leads to acetylation of intracellular proteins, inhibits cellular proliferation and induces apoptosis in leukemic cell lines. A phase Ia/II study was designed to determine the maximum-tolerated dose (MTD) of daily panobinostat, administered on two schedules: three times a week every week or every other week on a 28-day treatment cycle in patients with advanced hematologic malignancies. The criteria for hematologic dose-limiting toxicities differed between patients with indications associated with severe cytopenias at baseline (leukemia and myeloid disorders) and those less commonly associated with baseline cytopenias (lymphoma and …
Disseminated tuberculosis in a patient treated with a JAK2 selective inhibitor: a case report
2012
Abstract Background Primary myelofibrosis is a myeloproliferative disorder characterized by bone marrow fibrosis, abnormal cytokine expression, splenomegaly and anemia. The activation of JAK2 and the increased levels of circulating proinflammatory cytokines seem to play an important role in the pathogenesis of myelofibrosis. Novel therapeutic agents targeting JAKs have been developed for the treatment of myeloproliferative disorders. Ruxolitinib (INCB018424) is the most recent among them. Case presentation To our knowledge, there is no evidence from clinical trials of an increased risk of tuberculosis during treatment with JAK inhibitors. Here we describe the first case of tuberculosis in a…
Immunohistochemical evaluation of bone marrow lymphoid nodules in chronic myeloproliferative disorders
1991
One hundred and seventy bone marrow biopsies from patients with chronic myeloproliferative disorders (CMPDs) were evaluated for the presence of lymphoid nodules (LNs) and were immunostained using a panel of monoclonal antibodies (UCHL1, 4KB5 and L26) recognizing different lymphocyte antigens. LNs were found in 35% of cases of idiopathic thrombocythaemia, 24.6% of myelofibrosis/osteomyelosclerosis, 18.2% of polycythaemia vera 12.1% of chronic myeloid leukaemia and 19.2% of borderline cases. Varying degrees of immunohistochemical positivity for the three antibodies tested were found. LNs were always made up of variable proportions of both T- and B-lymphocytes with a prevalence of T-cells. Thi…
Janus kinase (JAK) 2 V617F mutation as the cause of primary thrombocythemia in acromegaly with severe visceromegaly and divergence between growth hor…
2012
OBJECTIVE: An increased prevalence of hematological abnormalities is reported in acromegaly, but to date no reports about the presence of the Janus Kinase (JAK) 2 mutation in acromegalic patients have been described. DESIGN: We report the complex clinical presentation of the unique case, never described, of acromegaly due to GH-secreting pituitary adenoma associated with JAK2 V617F mutation. RESULTS: The patient shows primary thrombocythemia and myelofibrosis, due to JAK2 V617F mutation, severe visceromegaly and a peculiar clinical course of the disease characterized by discrepant values of GH and IGF-1 during somatostatin analog (SA) treatment despite a significant reduction in pituitary a…
Allogeneic hematopoietic cell transplantation in older myelofibrosis patients: A study of the chronic malignancies working party of EBMT and the Span…
2021
Allogeneic hematopoietic cell transplantation (allo-HCT) is increasingly used in older myelofibrosis (MF) patients, but its risk/benefit ratio compared to non-transplant approaches has not been evaluated in this population. We analyzed the outcomes of allo-HCT in 556 MF patients aged > 65years from the EBMT registry, and determined the excess mortality over the matched general population of MF patients > 65years managed with allo-HCT (n=556) or conventional drug treatment (n=176). The non-transplant cohort included patients with intermediate-2 or high risk DIPSS from the Spanish Myelofibrosis Registry. After a median follow-up of 3.4years, the estimated 5-year survival rate, non-relapse mor…