Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MYELOFIBROSIS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 847 records · Page 47Linked to original sources
PubMed2000

[Allogeneic bone marrow transplantation for primary myelofibrosis after splenectomy].

A 46-year-old woman was given a diagnosis of primary myelofibrosis (PMF) in 1996. Because of the progression of anemia and splenomegaly, she was scheduled for allogeneic bone marrow transplantation (BMT) from an HLA-matched sibling donor in April 1998. Cyclophosphamide and busulfan were used as the conditioning regimen. Before BMT, the patient was treated with hydroxycarbamide, which did not resolve splenomegaly. She then underwent a splenectomy, which was followed by massive portal vein thrombosis without any significant clinical outcome. After BMT, the patient obtained rapid hematologic engraftment. Moreover, the alleviation of marrow fibrosis was confirmed 4 months after BMT. We concluded that allogenic BMT can cure patients with PMF, but that the issue of splenectomy and the indications for BMT need to be evaluated further.

Bone Marrow Transplantation↗
PubMed2000

Danazol treatment of idiopathic myelofibrosis with severe anemia.

BACKGROUND AND OBJECTIVE: Severe anemia is an important problem in patients with idiopathic myelofibrosis (IM). When other therapeutic measures are unsuccessful or not applicable, 40-50% favorable responses are obtained with androgen therapy. Oxymetholone is the drug usually employed, but good results have also been reported with danazol, although the experience is limited to a few patients. The aim of the present study was to evaluate the effect of danazol on the anemia of IM. DESIGN AND METHODS: Seven out of 22 consecutive IM patients were eligible for danazol treatment because of severe anemia not treatable with (four cases) or refractory to (three cases) other therapies. Danazol (600-800 mg/day) was given orally for six months and thereafter progressively tapered to the minimum effective dose in responding patients or discontinued in non-responders. Complete response was considered cessation of transfusion requirements with normalization of hemoglobin (Hb) values; partial response was defined as a > 30% reduction in transfusional needs or an increase > 10 g/L in the Hb. The effect on platelet counts was also analyzed. RESULTS: One patient splenectomized three years earlier achieved a complete response and three a partial response, giving an overall response rate of 57 %. A significant increase in platelet counts was also observed in three responders. The responses were first seen between three and six months after the start of treatment, which was usually well tolerated. INTERPRETATION AND CONCLUSIONS: Danazol, given at an appropriate dosage for a sufficient time, is an effective treatment for a substantial proportion of IM patients with severe anemia without marked splenomegaly or who have been previously splenectomized.

Adult↗
PubMed2000

Pathologic interaction between megakaryocytes and polymorphonuclear leukocytes in myelofibrosis.

Idiopathic myelofibrosis (MF) is a myeloproliferative syndrome characterized by an increase in bone marrow collagen. Megakaryocytes (Mks), which store growth factors in their alpha granules, are known to be involved in the pathogenesis of MF. Previously, mice given bone marrow grafts infected with a retrovirus carrying murine thrombopoietin (TPO) complementary DNA developed a disease resembling human idiopathic MF. In this study, we used this murine model (TPO mice) to determine whether release of alpha granules is responsible for fibroblast activation and development of fibrosis. The intracellular trafficking of several alpha-granule proteins (von Willebrand factor, fibrinogen, and transforming growth factor beta (TGF beta), which are stored in the granule matrix; and alpha(IIb)beta(3) integrin and P-selectin (CD62p), which are located in the alpha-granule membrane) was studied with immune electron microscopy in bone marrow Mks from TPO mice. P-selectin immunolabeling increased consistently and was occasionally found lining the demarcation membrane system. Evidence of extensive emperipolesis was also found in TPO mouse Mks, involving almost exclusively neutrophil and eosinophil polymorphonuclear (PMN) cells with altered morphologic features. In parallel, the host Mks had myeloperoxidase-positive granules scattered in their cytoplasm, associated with marked ultrastructural cytoplasmic alterations and ruptured alpha-granule membranes. Similar observations were made in bone marrow biopsy specimens from 12 patients with idiopathic MF; indeed, there was an increased rate of emperipolesis involving mostly PMN cells, abnormal P-selectin expression, and mutual subcellular PMN and Mk alterations. This study indicates that in idiopathic MF, abnormal P-selectin distribution in Mks induces selective sequestration of PMN cells. This results in a release of alpha-granular proteins and growth factors, which in turn induces fibroblast activation and fibrosis deposition. (Blood. 2000;96:1342-1347)

Animals↗
PubMed2000

Evaluation and clinical correlations of bone marrow angiogenesis in myelofibrosis with myeloid metaplasia.

Recent observations have underscored the biologic relevance of intratumoral angiogenesis and its potential impact on prognosis. Increased bone marrow angiogenesis has been demonstrated in a variety of hematologic disorders, including multiple myeloma. The extent and prognostic significance of bone marrow angiogenesis in 114 patients with myelofibrosis with myeloid metaplasia (MMM) was investigated. A control group of 44 patients without bone marrow disease, 15 patients with polycythemia vera, and 17 patients with essential thrombocythemia was also studied. Bone marrow microvessel density was assessed by a semiquantitative method, visual microvessel grading, and 2 separate quantitative methods, visual count and computerized image analysis. Angiogenesis estimation by all 3 methods was highly comparable. On visual microvessel grading, a grade 3 or 4 increase in bone marrow angiogenesis was demonstrated in 70% of patients with MMM, 33% of patients with polycythemia vera, 12% of patients with essential thrombocythemia, and 0% of normal controls. In a multivariate analysis, increased angiogenesis in MMM correlated significantly with increased spleen size and was found to be a significant and independent risk factor for overall survival. Increases in marrow angiogenesis correlated with hypercellularity and megakaryocyte clumping. In contrast, these 2 features were inversely proportional to reticulin fibrosis, whereas increases in marrow angiogenesis were independent of reticulin fibrosis. These preliminary findings suggest that neo-angiogenesis is an integral component of the bone marrow stromal reaction in MMM and may provide useful prognostic information and a rationale for the therapeutic investigation of anti-angiogenic agents.

Adult↗
PubMed1975

Static and functional morphology of the pathological platelets in primary myelofibrosis and myeloproliferative syndrome.

Native and functioning platelets in patients with primary myelofibrosis and myeloproliferative syndrome were examined by transmission electron microscopy. Among various types of ultrastructural abnormalities in the platelets, three features were emphasized: hypoplasia of the surface connecting system (SCS) with few orifices, hyperplasia of the dense tubular system, and considerable variety in numbers of granule. Morphological analysis was made on platelets of these patients and of normal subjects. Functional morphology of the abnormal platelets was examined in the aggregate samples either by ADP or collagen and the effluent blood from platelet retention test. The abnormal platelets were more or less indifferent from the aggregates and underwent only to a slight degree the changes observed in normal platelets. They frequently retained their native, round, smooth-surfaced form without pseudpod, and did not show the inward shift of organelles; furthermore, they retained more granules than did normal platelets. From these morphological findings we speculated that these ultrastructurally abnormal platelets had an impaired release reaction as a result of the dysfunction of SCS in passing released substances, of the inability of microfilaments to constrict in expelling these substances and sometimes because of a lack of granules as the sources.

Adenosine Diphosphate↗
PubMed1975

Pyruvate kinase deficiency anemia with terminal myelofibrosis and osteosclerosis in a beagle.

A 15-month-old male Beagle with chronic hemolytic anemia was found to have erythrocytic pyruvate kinase deficiency and, terminally, myelofibrosis and osteosclerosis. The dog's erythron was studied by procedures that enabled close comparison with congenital hemolytic anemia (pyruvate kinase deficiency) of Basenji dogs. The affected dog's sire, dam, and one littermate--each clinically and hematologically normal--were found to have 50% reduction in erythrocytic pyruvate kinase (PK) activity.

Ancylostomiasis↗
PubMed2001

[Splenectomy in 5 patients with idiopathic myelofibrosis].

Between 1992 and 1999, 5 patients with chronic idiopathic myelofibrosis (MF) underwent splenectomy at our hospital. The median age at the time of splenectomy was 63 years (range, 58-69 years), while the median interval from diagnosis of MF to splenectomy was 38.2 months (range, 3.7-87.2 months). Reasons for splenectomy included symptomatic splenomegaly in 5 patients, transfusion-dependent anemia in 5, and refractory thrombocytopenia in 3. Although most of the patients with transfusion-dependent anemia and thrombocytopenia showed some improvement at 1 month after splenectomy, the response was durable in only 2 patients at 6 months. Post-surgical thrombocytosis of 1020 x 10(9)/l was observed in one patient. Blast cell counts in peripheral blood increased after splenectomy in 4 patients. Leukemic transformation occurred in one patient 5 months after splenectomy. Four patients eventually died (2 of infection, 1 of acute myelocytic leukemia, and one of heart failure). Overall median survival was 54.7 months (range, 10.9-110.0 months) and 10.2 months (range, 6.0-33.6 + months) from diagnosis and time of splenectomy, respectively. We confirmed the palliative role of splenectomy in advanced-stage MF, but sufficient consideration should be given to late complications including blastic transformation.

Aged↗
PubMed2002

Myelofibrosis: response to busulfan after hydroxyurea failure.

We report a case of myelofibrosis with myeloid metaplasia (MMM) that responded dramatically to oral busulfan treatment after failure of hydroxyurea. Although busulfan treatment of this disease has fallen out of favour due to the favourable toxicity profile of hydroxyurea and reports of efficacy of interferon-alpha, our observation suggests there may still be a role for busulfan treatment of MMM in the setting of hydroxyurea or interferon failure or intolerance.

Alkylating Agents↗
PubMed2002

[CD25 positive chronic eosinophilic leukemia with myelofibrosis].

A 70-year-old man was referred to our hospital in March 2001 for the purpose of evaluation for anemia and thrombocytopenia. Physical examination revealed hepatosplenomegaly, normal skin, and normal neurologic findings. Blood examination showed a white blood cell count of 10,900/microliter, with a differential count of 58.5% eosinophils and 3.5% blast cells. Flow cytometric analysis of eosinophils revealed that they were positive for CD33, CD13, CD25, and HLA-DR. Bone marrow aspiration could not be performed due to dry tap, and bone marrow core biopsy specimen revealed severe myelofibrosis with blastoid cells proliferation. Cytogenetic analysis of bone marrow cells showed isochromosome 17. FISH analysis using a RAR alpha probe (17q21.1) demonstrated 62% of peripheral blood nucleated cells having three signals. BCR/ABL gene rearrangement by FISH analysis was not observed. Allergic disease, infectious disease, parasitic disease, collagen vascular diseases, pulmonary disease, and neoplastic disorders were excluded. Therefore, a diagnosis of chronic eosinophilic leukemia was made. The patient had no symptoms of hypereosinophilia. However, eosinophils with sparse granulation, positivity for CD25, elevated serum levels of soluble IL-2 receptor, and elevated serum levels of eosinophil cationic protein suggested activation of eosinophils. Further analysis is needed regarding the activation of eosinophils in chronic eosinophilic leukemia.

Aged↗
PubMed2003

Polycythemia vera in young patients: a study on the long-term risk of thrombosis, myelofibrosis and leukemia.

BACKGROUND AND OBJECTIVES: Polycythemia vera (PV) is unusual in young patients, so that little information is available on long-term clinical evolution in this particular group. The aim of this study was to define the long-term risk of thrombosis, acute leukemia (AL) and myelofibrosis with myeloid metaplasia (MMM) in young PV patients. DESIGN AND METHODS: From 1975 to 2000, 70 PV patients aged less than 50 years were followed for a median time of 14 years (range 2-26). About three quarters were treated with pipobroman. The Kaplan-Meier method and Cox regression were used for survival analysis. The standardized mortality ratio (SMR) was calculated using Italian age/sex specific mortality rates. RESULTS: The risk of thrombosis increased during the observation period, reaching a plateau of 14% at 10 years and was markedly higher in individuals with a previous history of thrombosis (p=0.0023). No patient had progression into AL or MMM before the 9th year of follow-up. Subsequently, five patients (7%) developed AL and five (7%) MMM, with a 20-year cumulative risk of 15% and 10%, respectively. Overall survival at 20 years was 62%, with nine patients dying of progression into AL or MMM, four of vascular events, one of lung cancer, and four of non-PV-related causes. The SMR was 5.3, indicating a mortality significantly higher than that of the general population (p<0.000). INTERPRETATION AND CONCLUSIONS: This long-term retrospective cohort study shows that although the median survival of young patients with PV exceeds 23 years, their life expectancy is markedly lower than that of the general population because of disease evolution into AL or MMM.

Adolescent↗
PubMed1976

Splenectomy and myelofibrosis.

Two patients are reported in whom splenectomy during the course of myelofibrosis was followed by rapid deterioration in the function of a previously involved liver, and was characterised by refractory ascites, increasing jaundice, and death. It is important to recognise this complication, since ectopic haematopoiesis can be demonstrated on liver biopsy and, perhaps, controlled with radiotherapy or cytotoxic chemotherapy.

Female↗
PubMed2003

Critical review of pathogenetic mechanisms in myelofibrosis with myeloid metaplasia.

Myelofibrosis with myeloid metaplasia is an uncommon chronic myeloproliferative disorder characterized by extramedullary hematopoiesis associated with varying degrees of bone marrow fibrosis (hematopoiesis is clonal and fibrosis is a polyclonal reactive process). The primary defect in a pluripotent stem cell is still unknown. However, advances have been made during the past few years in the knowledge of the pathogenetic mechanisms in this disorder. This review focuses on current data on the cellular and molecular mechanisms possibly participating in the development of the disease.

Growth Substances↗
PubMed2003

Myelofibrosis with myeloid metaplasia: therapeutic options in 2003.

Myelofibrosis with myeloid metaplasia (MMM) is a progressive, clonal, and lethal myeloproliferative disorder with a variable prognosis. The only potentially curative therapy for MMM is allogeneic stem cell transplantation, but this therapy is too toxic for older patients and inappropriate for young patients with good prognostic features. A nonmyeloablative or autologous stem cell transplant may broaden the applicability of high-dose therapy for MMM, but the therapy for MMM is palliative in intent and aimed at symptomatic relief. There is no approved therapy for MMM; however, certain agents have been useful for targeted palliation. Myelosuppressive drug therapy, targeted radiation, or splenectomy has decreased symptomatic myeloproliferation (i.e., splenomegaly). MMM-associated cytopenias may be improved by the selective use of growth factors, androgens, and thalidomide. Debilitating constitutional symptoms improve with the pharmacologic blockage of tumor necrosis factor-alpha. Further molecular understanding of MMM is necessary for more effective targeted therapies.

Antineoplastic Agents↗
PubMed1992

[Ferrokinetic studies in the initial evaluation of idiopathic myelofibrosis: results in 18 patients].

BACKGROUND: Since there is no effective treatment for idiopathic myelofibrosis (IM) the determination of possible factors which are involved in the appearance of anemia in this disease may be important from a practical point of view. METHODS: The results of the initial ferrokinetic study analyzed in 18 patients with IM included plasma clearance (T1/2) and globular incorporation (U max) of 59Fe in addition to the uptake of 59Fe in the sacrum, spleen and liver in 16 patients. The clinical-hematologic and histologic data of the different groups of patients identified according to the results of the study were compared. RESULTS: Three ferrokinetic patterns were observed: 1) normal or increased erythropoiesis (8 patient), 2) inefficient erythropoiesis (7 patients), and 3) aplastic pattern (3 patients). The only difference observed between the three groups was the existence of lower levels of Hb and reticulocytes in the subjects with aplastic type pattern. In contrast, although there was an inverse correlation between the medullar and extramedullar uptake of iron (p = 0.018) no relation was observed between the latter and the size of the spleen or liver. CONCLUSIONS: The results obtained in this study indicate that IM behaves heterogeneously from a ferrokinetic point of view.

Adult↗
PubMed2003

Circulating hematopoietic progenitor cells predict survival in patients with myelofibrosis with myeloid metaplasia.

BACKGROUND AND OBJECTIVES: The levels of circulating hematopoietic progenitor cells are often increased in myelofibrosis with myeloid metaplasia (MMM). The prognostic relevance of this phenomenon is largely unknown. DESIGN AND METHODS: We determined the number of circulating myeloid (CFU-GM), erythroid (BFU-E), and pluripotent (CFU-GEMM) progenitors, in 110 patients with MMM at diagnosis using a semi-solid colony assay. Overall survival was investigated by plots of the Kaplan-Meier estimator; known risk factors and the number of circulating progenitor cells were tested by univariate and multiple Cox regression analysis. RESULTS: Univariate analysis showed that hemoglobin concentration (p=0.019), CFU-GM (p< 0.0001), BFU-E (p=0.002), and age (p=0.002) predicted survival. Numbers of circulating CFU-GM above the 75th percentile were associated with a significantly shorter survival than were CFU-GM levels at or below the 75th percentile (27 vs. 74 months, p=0.0007). Similarly, high numbers of BFU-E in peripheral blood (> 75th percentile) predicted a shorter survival (33 vs. 74 months; p=0.007). When myeloid and erythroid progenitor cells were calculated separately in the multiple Cox regression analysis, both CFU-GM (hazard ratio 2.8, 95% CI, 1.35 to 5.93) and BFU-E (hazard ratio 2.57, 95% CI, 1.26 to 5.21) numbers above the 75th percentile were independent adverse prognostic factors in our patients. INTERPRETATION AND CONCLUSIONS: High levels of circulating myeloid and erythroid progenitor cells are novel risks factors in patients with MMM. The assessment of hematopoietic progenitor cells may be useful to determine risk-adjusted treatment strategies.

Adult↗
PubMedDate not supplied

[Myelofibrosis with myeloid metaplasia. A study of 24 consecutive patients].

A series of 24 consecutive patients affected by myelofibrosis with myeloid metaplasia was reviewed. The clinical-pathological features at onset were similar to those reported in literature; in particular in all the patients we observed splenomegaly and the typical leuko-erythroblastic picture in peripheral blood. The median survival of our series was of 57 months; the deaths were caused by severe anaemia and/or infection and/or haemorrhage; the blastic terminal transformations were rare. According to other authors, unfavourable prognostic factors in our patients were: male sex, advanced age, hepatomegaly, the presence of systemic signs, anaemia, leukocytosis, leukopenia, high number of circulating erythroblasts, thrombocytopenia, osteomyelosclerosis. We have confirmed the clinical value of three staging prognostic systems: the system proposed by Njoku based on haemoglobin level and reticulocytes number, the system proposed by Visani based on haemoglobin and circulating myeloid precursors number, the system proposed by Dupriez based on haemoglobin and white blood cells number.

Adult↗
PubMedDate not supplied

Platelet abnormalities in idiopathic myelofibrosis: functional, biochemical and immunomorphological correlations.

BACKGROUND: An extensive study of platelet function was performed on 18 consecutive patients affected by idiopathic myelofibrosis (IM). MATERIALS AND METHODS: Clinical hematological and morphofunctional parameters were studied in IM patients and control subjects. Platelet tests, ultrastructural data, immunocytochemical von Willebrand factor detection, freeze fracturing results and free cytosolic calcium level were evaluated. RESULTS: Bleeding time was frequently found to be prolonged, but it never reached levels which could give any cause for concern. Aggregation by ADP, collagen and epinephrine was always altered, sometimes profoundly; on the contrary, agglutination by ristocetin was almost always normal, albeit occasionally increased. Plasma beta-TG and PF4 levels were found to be elevated in 11 and 12 patients, respectively. This indicated an abnormal release from platelet alpha-granules. Depletion of alpha-granules was also confirmed by the intraplatelet von Willebrand factor (vWF) labelling with colloidal gold particles bound to polyclonal antibodies against human vWF. In fact: 1) the number of positive alpha-granules/microm2 and per single platelet was reduced; 2) the intensity of the immunocytochemical reaction for single positive alpha-granules and for each platelet was significantly reduced. Freeze-fracturing studies showed an increase in the number of intra-membrane particles (IMP) on the P face of the platelet membrane with respect to normal platelets preincubated with ADP. However, no differences in their distribution or diameter were observed. High concentrations of free cytosolic calcium were always found and Ca++ ATPase activity was increased. Conversely, Na+/K+ ATPase activity was always reduced. CONCLUSIONS: We can hypothesize that the platelet membrane is altered in IM, resulting in facilitated activation, even by subliminal stimuli, and that this continuous platelet activation ultimately leads to alpha-granule depletion.

Adenosine Diphosphate↗