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.

SourceResearch connectionFrom yearThrough year

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

At least 253 records · Page 14Linked to original sources

PubMed1979

Acquired hemoglobin H disease in idiopathic myelofibrosis.

A 68-year-old male, diagnosed 1 year previously as having myelofibrosis, developed hemolysis, red cell inclusions, and 37% Hb H. The alpha/beta globin synthetic ratio for circulating reticulocytes, determined by 3H-leucine incorporation and globin chain separation by carboxymethylcellulose chromatography in urea, was 0.049. When total RNA was purified from peripheral blood cells and translated in a wheat germ cell-free translation system, the alpha/beta ratio of the translation products was 0.26, indicating mRNA as a major cause of the globin synthetic imbalance. This study demonstrates that myelofibrosis is one setting in which acquired Hb H disease occurs; that the synthetic imbalance may be extreme; and that it can be associated with an imbalance in the activities of specific globin mRNAs.

Aged↗

PubMed1986

Serum markers for type IV collagen and type III procollagen in the myelofibrosis-osteomyelosclerosis syndrome and other chronic myeloproliferative disorders.

Myelofibrosis is characterized by excessive deposition of interstitial and basement membrane collagens in the bone marrow. In this study, specific radioimmunoassays for the aminoterminal propeptide of type III procollagen and for the 7S collagen domain of type IV (basement membrane) collagen were used to determine how this accumulation is reflected in serum. Of the 41 patients with chronic myeloproliferative disorders studied, the highest levels of both parameters were found in idiopathic myelofibrosis and in chronic myelogenous leukaemia associated with bone marrow fibrosis. Increasing degrees of bone marrow fibrosis were accompanied by increasing serum concentrations of both markers, except for osteomyelosclerosis, where notably low values were seen. Pathologically high values of one or both parameters were also found in a few patients with polycythaemia vera or a transitional myeloproliferative disorder. The antigens related to type III procollagen and type IV collagen correlated significantly with each other and with the leucocyte count. These parameters should provide noninvasive means for following the accumulation of interstitial and basement membrane collagens in the bone marrow.

Adult↗

PubMed1989

Idiopathic myelofibrosis terminating in erythroleukemia.

A 55-year-old woman with a one-year history of idiopathic myelofibrosis progressed to erythroleukemia. This is the first reported occurrence of erythroleukemia progression from idiopathic myelofibrosis. Certain patterns of leukemia transformation from myeloproliferative disorders are favored: Myeloblastic or myelomonocytic. The rare incidence of erythroblastic transformation is discussed.

Biopsy↗

PubMed2005

Significance of myelofibrosis in early chronic-phase, chronic myelogenous leukemia on imatinib mesylate therapy.

BACKGROUND: Myelofibrosis is associated historically with a poor prognosis in patients with chronic myelogenous leukemia (CML). Its significance in the recent era of effective therapy with imatinib mesylate is unknown. METHODS: The current study evaluated the significance of the degree of pretreatment myelofibrosis on response and survival with imatinib therapy in patients with newly diagnosed CML. The study group comprised 198 patients with newly diagnosed Philadelphia chromosome-positive, chronic-phase CML treated with imatinib mesylate therapy. They were analyzed for the prognostic significance of bone marrow reticulin fibrosis. RESULTS: Severe reticulin (Grade 3-4) fibrosis was observed in 75 patients (38%): Grade 3 in 46 (23%) patients and Grade 4 in 29 (15%) patients. There was a trend towards a lower incidence of a complete cytogenetic response in patients with Grade 4 reticulin fibrosis (76% vs. 89%; P = 0.07), and a significantly worse survival (estimated 3-year survival rate of 87% vs. 97%; P = 0.04). CONCLUSIONS: Although the prognostic significance of severe reticulin fibrosis in patients with newly diagnosed CML receiving imatinib therapy was better, 15% of patients with Grade 4 reticulin fibrosis still had a worse outcome.

Adolescent↗

PubMed2006

Presence of unfavorable cytogenetic abnormalities is the strongest predictor of poor survival in secondary myelofibrosis.

BACKGROUND: Postpolycythemic (PV) and postthrombocythemic (ET) myeloid metaplasia are consensually referred to as secondary myelofibrosis (sMF). Prognostic variables in sMF are not as well defined as they are for de novo myelofibrosis with myeloid metaplasia (MMM), which is also known as agnogenic myeloid metaplasia (AMM). Such information is particularly crucial for management decisions in transplant-eligible patients. METHODS: Diagnoses of PV and ET required fulfillment of the World Health Organization criteria for the diagnosis of MMM as well as an antecedent history of either polycythemia vera or essential thrombocythemia that was supported by bone marrow examination. Cytogenetic findings were classified as being either favorable (normal or isolated 13q- or 20q- clones) or unfavorable (presence of abnormalities other than 13q- and 20q-). RESULTS: The study population was comprised of 66 young patients (age <60 yrs) with sMF, including 37 patients with PV and 29 patients with ET. Multivariate analysis of parameters other than cytogenetics identified older age (P = .02), anemia (hemoglobin level <10 g/dL [P = .007]), and PV (P = .009) to be independent risk factors for shortened survival. However, when such analysis was restricted to patients in whom cytogenetic studies were performed (n = 31 patients), the presence of unfavorable cytogenetic abnormalities (i.e., clones other than 20q- and 13q-) became the only adverse prognostic factor for survival (P = .001). A similar analysis in a temporal cohort of 50 age-matched patients with AMM also identified unfavorable cytogenetics as an independent predictor of poor survival, along with thrombocytopenia and anemia. CONCLUSIONS: The results of the current study suggest that cytogenetic findings might supersede AMM-derived prognostic scoring systems for predicting survival in patients with sMF.

Adult↗

PubMed2006

Palliative goals, patient selection, and perioperative platelet management: outcomes and lessons from 3 decades of splenectomy for myelofibrosis with myeloid metaplasia at the Mayo Clinic.

BACKGROUND: Although splenectomy may palliate massive splenomegaly in patients with myelofibrosis with myeloid metaplasia, this procedure carries significant risks. The authors retrospectively analyzed their experience with splenectomy over the course of 30 years to analyze the impact of improved techniques, antimicrobials, and aggressive postoperative control of platelet counts on outcome. METHODS: A total of 314 patients underwent splenectomy between 1976 and 2004 for mechanical symptoms (= 156 patients [49%]), anemia (= 78 patients [25%]), portal hypertension (= 47 patients [15%]), or thrombocytopenia (= 33 patients [11%]). Of a total of 91 patients studied during the last decade, 69 patients (76%) experienced a palliative benefit for their primary surgical indication for a median of 12 months (range, 1-91 months). RESULTS: Perioperative complications occurred in 87 patients (27.7%) including infection (= 31 patients [9.9%]), thrombosis (= 31 patients [9.9%]), or bleeding (= 44 patients [14%]), 21 of which (6.7% of all patients) were fatal. Perioperative thrombohemorrhagic complications decreased in the last decade through the use of platelet apheresis and the prompt use of cytoreductive agents to counteract postsplenectomy thrombocytosis. Survival after splenectomy was found to be decreased in patients with preoperative thrombocytopenia (<100 x 10(9)/L [P = 0.006]) but not by indication, myelofibrosis with myeloid metaplasia (MMM) prognostic score, or the decade in which splenectomy was performed. CONCLUSIONS: The lack of improvement in overall postsplenectomy survival over time may be a reflection on the failure of medical therapy to improve survival in patients with MMM.

Adolescent↗

PubMedDate not supplied

Angiofollicular lymph node hyperplasia associated with myelofibrosis case report and immunologic marker studies.

A case of angiofollicular lymph node hyperplasia (AFH) (hyaline vascular type) of the mediastinum associated with myelofibrosis is reported with immune marker studies. We hypothesize that the myelofibrosis is more than a mere coincidence since other myeloproliferative disorders have been observed in conjunction with AFH. Immunohistochemistry on cryostat sections of lymph node using the biotin-avidin fluorescence technique showed the presence of numerous T helper cells and very few T suppressor/cytotoxic cells in the parafollicular areas. Concentric rings of lymphocytes showed the phenotype of mantle zone lymphocytes (i.e. IgM, IgD positivity), while the germinal centres were ill-formed as shown by Leu 14 (a Pan B cell marker) staining. By electron microscopy, follicular dendritic reticulum cells were readily found. The above findings suggest an abnormality of germinal center formation.

Antigens, Differentiation↗

PubMed2001

Risks and benefits of splenectomy in myelofibrosis with myeloid metaplasia: a retrospective analysis of 26 cases.

BACKGROUND AND OBJECTIVES: To evaluate the outcomes of splenectomy in myelofibrosis and myeloid metaplasia (MMM). METHODS: We retrospectively reviewed our records of 26 patients with MMM who underwent an open splenectomy at Boston University Medical Center between 1979 and 1995. Fourteen patients had agnogenic myeloid metaplasia (AMM) and 12 had myelofibrosis with antecedent myeloproliferative disorders (MF). The main indications for splenectomy were progressive transfusion-dependent anemia, painful splenomegaly, and hypercatabolic symptoms associated with cytopenia. RESULTS: Median time to splenectomy after the diagnosis of MMM was 29 months ranging from 1 to 96 months. Three patients (11%) died within 1 month after the surgery because of sepsis. The most common peri- and postoperative complications were pneumonia and other bacterial infections (42%), cardiac events (19%), acute bleeding (15%), ileus (15%), and venous thrombosis (12%). Of the eight surviving patients who underwent splenectomy for transfusion dependent anemia, six (75%) had improvement in their hematocrit levels with abolishment of blood transfusions. A durable symptomatic palliation was achieved in all patients. Liver enlargement was noted in seven patients at 1-year evaluation. None of these patients developed hepatic failure. Leukemic transformation occurred in 8 of 18 patients (44%) postsplenectomy. The median overall survival for the entire group was 58.5 and 28 months from the diagnosis of MMM and the time of splenectomy, respectively. There was no difference in survival rates between patients with AMM and MF. CONCLUSIONS: Splenectomy is an effective palliative procedure with an acceptable morbidity in selected patients with MMM. Progressive transfusion-dependent anemia should also be considered an indication for splenectomy in the absence of leukemic evolution.

Adult↗

PubMed1998

Myelofibrosis: experimental models and human studies.

Thrombopoietin (TPO) is the central regulator of megakaryocytopoiesis and thrombocytopoiesis. Preclinical data and human studies have so far shown that the recombinant molecule is safe to administer and associated with very little toxicity. Nevertheless, different experimental animal models have revealed that a chronic exposure to very high doses of TPO could result in myeloproliferative syndromes with a spectrum of pathological features in common with human idiopathic myelofibrosis (PMF). A number of investigators have researched whether TPO or its receptor Mpl were involved in the pathogenesis of human myeloproliferative syndromes which are also characterized by a predominant megakaryocytic involvement, in PMF and primitive essential thrombocythemia. In both diseases, megakaryocyte (MK) progenitors develop autonomously in serum-deprived cultures. This spontaneous MK development is also observed at limiting dilution demonstrating that MK escape the normal regulatory controls. Furthermore, this abnormal MK proliferation and maturation is neither due to an autocrine stimulation by TPO nor by point mutation or deletion in the coding region of the c-mpl gene. This paper will review the data that have been reported to date on the effects of an overexpression of Mpl ligand and related molecules on the induction of experimental myelofibrosis and highlight recent insights into the pathogenesis of PMF.

Animals↗

PubMed1975

Gd(--) Abrami: a deficient G-6PD variant with hemizygous expression in blood cells of a woman with primary myelofibrosis.

A new deficient G-6PD variant, Gd(--) Abrami, was found in granulocytes, platelets and red blood cells of a 65-year-old woman with myelofibrosis. Enzyme and immunological titrations showed that only the deficient variant was present in blood cells whereas both the normal and abnormal enzymes were found in the fat cells of this patient. These results seem to indicate that the granulocytes, platelets and erythrocytes of this woman with myelofibrosis have arisen from a single abnormal precursor the functional X chromosome of which is the one carrying the abnormal G-6PD gene.

Adipose Tissue↗

PubMed1982

Cytogenetic studies using HPCM-stimulated short-term liquid cultures of circulating hemopoietic precursor cells in patients with myelofibrosis.

Cytogenetic studies were performed on nine patients with myelofibrosis. Mononuclear cells from the peripheral blood were cultured for two days in the presence of human placenta-conditioned medium (HPCM) prior to the preparation of metaphases. Two patients showed abnormal clones. In one of them the Y chromosome was missing. In the other patient the abnormal clone was characterized by the involvement of the chromosomes 7 and 9 (46,XX,7q-,-9,+mar). The significance of cytogenetically abnormal circulating hemopoietic precursor cells in patients with myelofibrosis is discussed.

Adult↗

PubMed1988

Interferon-alpha-2 in the treatment of idiopathic myelofibrosis.

We investigated the effect of human recombinant DNA-derived IFN-alpha-2 given in a dose of 1-2 X 10(6) units daily by subcutaneous injection to five patients with advanced idiopathic myelofibrosis (IM). Transfusion dependent anemia and symptomatic splenomegaly were taken as inclusion criteria for this pilot study. Two patients succumbed, one and three months after starting interferon-treatment because of pneumonia and traumatic cranial injury, respectively. While on IFN-treatment no improvement of cytopenia or reduction of splenomegaly was seen in four of the patients. In one patient, however, the requirement for erythrocyte transfusions decreased from 5 to 1.7 monthly upon IFN-treatment. After two, four and six months respectively IFN-treatment had to be stopped in these cases because of progressive thrombocytopenia and/or neutropenia. These observations suggest, that IFN-alpha might be of only marginal value in the treatment of advanced idiopathic myelofibrosis.

Aged↗

PubMed1985

Myelofibrosis arising in treated histiocytosis X.

Myelofibrosis, or fibrous replacement of hematopoietic bone marrow, is rarely encountered in pediatric patients. An unusual, reversible case arising in the setting of treated histiocytosis X is reported, a previously undescribed association. The clinical, pathologic, radiographic, and scintigraphic characteristics of myelofibrosis are reviewed.

Antineoplastic Agents↗

PubMed1978

Oxymetholone treatment in myelofibrosis.

In order to study the effect of oxymetholone therapy in advanced myelofibrosis, 11 patients (4 females, 7 males) were given, 3--5 mg per kg body weight, long-term oxymetholone treatment in a prospective multicenter study. Five cases had previously had a diagnosis of polycythemia vera. All patients had anemia initially, 4 leukocytopenia and 10 thrombocytopenia in addition. Hepato-splenomegaly was present in all cases but in varying degree. Five patients required regular blood transfusions before treatment. In 9 of the 15 courses given, there was normalization of the peripheral blood or substantial improvement (better than 3 g hemoglobin/dl or 50 X 10(9) platelets/1) after androgens. Significant effects were noted both on hemoglobin values and platelet counts. The need for blood transfusions ceased completely in all 5 cases. When oxymetholone treatment was reduced or interrupted 4 patients relapsed; 2 of them responded to a renewed course. The red cell counts returned to previous polycythemic values in one patient and another died from acute leukemia. The results of this study suggest that androgens might be of value in advanced cases of myelofibrosis with transfusion-requiring anemia or severe thrombocytopenia.

Aged↗

PubMed1992

The impact of megakaryocyte proliferation of the evolution of myelofibrosis. Histological follow-up study in 186 patients with chronic myeloid leukaemia.

A histological study on sequential bone marrow biopsies in patients with chronic myeloid leukaemia (CML) was performed. We wished to answer the question as to whether a different content of megakaryopoiesis in the bone marrow of CML patients has a prognostic significance for the development of myelofibrosis during the course of disease. In addition, the significance of possible changes in the quantity of megakaryopoiesis in this process was assessed. In 186 patients who had no fibre increase at first diagnosis, the rate of subsequent myelofibrosis varied from 19% for the common or granulocytic subtype (CML.CT) to 40% for patients with features of megakaryocytic increase (CML.MI). No significant differences were found either in the rapidity of progression to fibrosis or in the final rate of osteomyelosclerosis. Whereas in CML.MI most patients (75%) showed an increase of fibres only, this was accompanied by an additional increase of megakaryocytes in CML.CT, changing the histological pattern from CML.CT to .MI or .MP, respectively. The data therefore revealed a correlation between fibre increase and subtyping of CML as suggested by the Hannover classification of chronic myeloproliferative diseases. Subtypes of CML with megakaryocytic increase could be shown to present a "pre-myelofibrotic" stage of disease and may therefore be conceived as a particular pathway of acceleration.

Biopsy↗

PubMed1991

Vitamin D dependent rickets type II with myelofibrosis and immune dysfunction.

We present a new patient with vitamin D dependent rickets type II. A 20-month-old Arabian boy whose parents are first cousins showed florid rickets, myelofibrosis and recurrent septicaemia. In addition to absent specific binding for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). 25-Hydroxyvitamin D3-24-hydroxylase activity could not be induced in cultured fibroblasts. The patient did not respond to 99 micrograms 1,25(OH)2D3 per day, but skeletal and haematological abnormalities improved with daily infusion of 100 mg/kg calcium, as serum parathyroid hormone levels fell to normal values. At the age of 7 years, he died from pneumonia. The improvement of haematological abnormalities with calcium infusions but not with 1.25(OH)2D3 suggests a pathogenetic relationship of myelofibrosis and hyperparathyroidism. Having anti-lipid A IgM antibody titres up to 1:10.000 after Gram negative septicaemias, the patient never produced corresponding IgG antibodies. His neutrophil chemotaxis was persistently reduced to 57% +/- 3% of age-matched controls (P less than 0.028). The patient showed two pathological immune functions considered to contribute to the well-known susceptibility to infection in rickets.

Calcium↗

PubMed1985

Stromal cells in primary myelofibrosis: ultrastructural observations.

The bone marrows of five patients with primary myelofibrosis at different stages of the disease have been studied. In the myelofibrotic bone marrow, associated with "reticulum cells", two other cell types have been identified, namely fibroblast-like and myofibroblast-like reticulum cells, as well as a spectrum of transitional forms. Our findings suggest that reticulum cells may represent a reserve stromal cell pool (i.e. primitive reticulum cells) able to modulate themselves and to transform differently according to functional requirements. Some suggestions regarding the functional significance of fibroblast-like and myofibroblast-like reticulum cells in primary myelofibrosis are suggested.

Biopsy↗

PubMed1978

Cytogenetics of acute and chronic myelofibrosis.

In myelofibrosis, acute or chronic, as well as in other myeloproliferative disorders which carry an increased risk of developing leukemia, a clone of hemic cells with a chromosome abnormality is a relatively common occurrence. To date, however, the presence or absence of a cytogenetic alteration has not been of prognostic value with respect to subsequent clinical course. No particular karyotypic change is specific for myelofibrosis, but many of the same non-random abnormalities occur as in other leukemic and preleukemic states. Both cytogenetic and isoenzyme data indicate that the fibrous tissue in the marrow is not part of the myeloproliferative clone.

Acute Disease↗