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Biomedical subjects

A Tefferi

Publications and source records attributed to A Tefferi.

At least 145 records · Page 8Linked to original sources
PubMed1997

Acquired von Willebrand's disease due to aberrant expression of platelet glycoprotein Ib by marginal zone lymphoma cells.

A 69-year-old woman presented with splenic marginal zone lymphoma associated with acquired von Willebrand's disease (AVWD). Laboratory abnormalities included markedly decreased plasma levels of factor VIII coagulant (C) activity (VIII:C 28%), von Willebrand's factor (VWF) antigen (Ag) (vWF:Ag < 6%), and VWF ristocetin cofactor (RCo) activity (VWF:RCo, < 12%). VWF multimer analysis revealed a severe type II defect. Treatment with cryoprecipitate, high-dose gamma globulin or desmopressin given intravenously was unsuccessful. Clinical bleeding and coagulation abnormalities showed transient improvement after replacement therapy with Humate-P concentrate. The coagulation abnormalities improved partially after splenectomy and completely after subsequent chemotherapy. The neoplastic lymphocytes in the blood and spleen strongly expressed platelet glycoprotein Ib (CD42) and VWF but not other platelet-associated antigens.

Aged↗
PubMed1997

Anagrelide as a new platelet-lowering agent in essential thrombocythemia: mechanism of actin, efficacy, toxicity, current indications.

Anagrelide is an oral imidazoquinazoline agent with an anti-cyclic AMP phosphodiesterase activity and inhibits platelet aggregation in both humans and animals. In addition, it has in humans a species-specific platelet-lowering activity observed at dose levels lower than those required to inhibit platelet aggregation. Because of this, the drug has been tested in patients with clonal thrombocytosis and has been shown to have potent platelet-reducing activity in essential thrombocythemia (ET) and related disorders. The mechanism of action may involve the drug's interference with megakaryocyte maturation. More than 90% of patients with ET respond to anagrelide regardless of the presence or absence of previous therapy. The responses are durable with a median maintenance dose of approximately 2 to 2.5 mg/day. Side effects are related mostly to the drug's direct vasodilating and positive inotropic effects and include headache, fluid retention, tachycardia, and arryhthmias. The place of anagrelide therapy in the current management of patients with ET is discussed.

Animals↗
PubMed1997

Interferon-alpha therapy in polycythemia vera and essential thrombocythemia.

Essential thrombocythemia (ET) and polycythemia vera (PV) are chronic clonal myeloid disorders that originate from the multipotential hematopoietic stem cell. They are characterized, respectively, by excessive thrombocytosis and erythrocytosis, a high incidence of thrombohemorrhagic events, vasomotor symptoms, and an inherent tendency to undergo leukemic transformation. Current standard therapies to control the excess accumulation of myeloid cells and to provide symptomatic relief carry either a persistent risk of thrombosis, as in the case of phlebotomy, or, in the case of hydroxyurea, the potential for inducing leukemia. None alter the natural history of these diseases. Interferon-alpha has been shown to have potent antiproliferative effects on the hematopoietic stem cells and bone marrow fibroblasts and, as a result, has received much attention as a therapeutic agent for chronic myeloproliferative disorders. The ability of interferon-alpha to induce hematologic and cytogenetic remission in chronic phase chronic granulocytic leukemia has further increased interest in this agent. Interferon-alpha has shown therapeutic activity in PV and ET, as demonstrated in multiple small studies and single-arm trials reviewed in this article. Reported beneficial effects include the ability to control excessive erythrocytosis and thrombocytosis and such disease-related features as vasomotor symptoms, pruritus, and splenomegaly. Recent reports of cytogenetic remission and reversal of bone marrow fibrosis after interferon therapy are of interest. Advantages over current therapeutic standards include lack of known leukemogenic and teratogenic effects and the potential to alter the underlying course of disease. Nevertheless, none of the information available allows definite therapeutic recommendations for the use of interferon-alpha in PV or ET. The available data support the need for randomized controlled trials comparing interferon-alpha with standard therapy.

Cell Division↗
PubMed1997

Practical aspects in the diagnosis and management of aplastic anemia.

Aplastic anemia may result from several pathogenic mechanisms, the most common is idiopathic. The current definitive treatments for aplastic anemia are bone marrow transplantation (BMT) or immunosuppressive (IS) therapy. The benefits of each are comparable. However, certain subsets of patients derive superior benefit from one or the other. Bone marrow transplantation is the initial treatment of choice for young patients (< 20 years old). It results in the complete reconstitution of hematopoiesis, whereas autologous hematopoietic remissions after IS therapy are more susceptible to relapse. Survival rates after BMT, in patients between the ages of 20 and 40, are comparable to those reported for IS therapy. Better survival rates after BMT have been achieved with improved conditioning regimens and graft-versus-host disease prophylaxis. For patients older than 40, the treatment of choice is IS. Long-term complications of IS therapy include recurrence and development of clonal myeloid disorders. Long-term complications after BMT include graft-versus-host disease and secondary neoplasms. The IS regimen includes the combination of antithymocyte globulin and cyclosporin A. The addition of growth factor to the IS regimen seems promising; however, their use on their own is not recommended. Androgens have been shown to be inferior in the treatment of aplastic anemia. The role of BMT from an unrelated donor is being investigated.

Anemia, Aplastic↗
PubMed1997

The neurologic complications of B-cell chronic lymphocytic leukemia.

We performed a retrospective study to characterize the type, frequency, and timing of neurologic complications in patients with B-cell chronic lymphocytic leukemia (B-CLL). We reviewed 962 total charts with a median follow-up time of 57.5 months. There were 109 cases (11.3%) of neurologic complications, including 69 cases (7.2%) of herpes zoster infection, 17 cases (1.8%) of other opportunistic infection, 14 cases (1.5%) of treatment-related conditions, eight cases (0.8%) of direct leukemic involvement of neural tissue, and 1 case (0.1%) of intracranial hemorrhage. No cases of a non-zoster opportunistic infection presented in early-stage (Rai stage 0-2) B-CLL, and only one case of direct leukemic involvement of neural structures presented in early-stage B-CLL. Of the 25 cases of non-zoster or treatment-related complications, only 5 presented before 6 years from the initial B-CLL diagnosis. Three of these were in advanced-stage B-CLL, staging could not be determined in one, and one presented in early-stage B-CLL. We conclude that the overall neurologic complication rate of B-CLL is low, and that the Rai stage of the disease correlates best with the risk of developing neurologic complications. The occurrence of a related non-zoster neurologic complication in a patient with B-CLL stage 0-2 approaches 1:1,000.

Adult↗
PubMed1997

Environmental chemical exposures and disturbances of heme synthesis.

Porphyrias are relatively uncommon inherited or acquired disorders in which clinical manifestations are attributable to a disturbance of heme synthesis (porphyrin metabolism), usually in association with endogenous or exogenous stressors. Porphyrias are characterized by elevations of heme precursors in blood, urine, and/or stool. A number of chemicals, particularly metals and halogenated hydrocarbons, induce disturbances of heme synthesis in experimental animals. Certain chemicals have also been linked to porphyria or porphyrinuria in humans, generally involving chronic industrial exposures or environmental exposures much higher than those usually encountered. A noteworthy example is the Turkish epidemic of porphyria cutanea tarda produced by accidental ingestion of wheat treated with the fungicide hexachlorobenzene. Measurements of excreted heme precursors have the potential to serve as biological markers for harmful but preclinical effects of certain chemical exposures; this potential warrants further research and applied field studies. It has been hypothesized that several otherwise unexplained chemical-associated illnesses, such as multiple chemical sensitivity syndrome, may represent mild chronic cases of porphyria or other acquired abnormalities in heme synthesis. This review concludes that, although it is reasonable to consider such hypotheses, there is currently no convincing evidence that these illnesses are mediated by a disturbance of heme synthesis; it is premature or unfounded to base clinical management on such explanations unless laboratory data are diagnostic for porphyria. This review discusses the limitations of laboratory measures of heme synthesis, and diagnostic guidelines are provided to assist in evaluating the symptomatic individual suspected of having a porphyria.

Environmental Exposure↗
PubMed1997

Chronic granulocytic leukemia: recent information on pathogenesis, diagnosis, and disease monitoring.

Current evidence strongly implicates the chromosome translocation t(9;22)(q34;q11.2) as the cause of chronic granulocytic leukemia. Therefore, identification of this genetic abnormality through either cytogenetic or molecular methods has become a requirement for diagnosis. Intense investigation of the mechanism by which t(9;22) transforms normal hematopoietic progenitors into malignant cells is ongoing. Recent advances in molecular diagnostic methods have allowed refined qualitative and quantitative methods of detecting t(9;22), which are useful for monitoring response status and detecting minimal residual disease. The current understanding of the pathogenesis of chronic granulocytic leukemia and the application of new diagnostic methods are discussed.

Blotting, Southern↗
PubMed1996

Pure red cell aplasia: association with large granular lymphocyte leukemia and the prognostic value of cytogenetic abnormalities.

From 1980 through 1994, we identified 47 adult patients with acquired pure red cell aplasia (median age, 64 years; range, 22 to 84 years). Associated clinical disorders included T-cell large granular lymphocytic (LGL) leukemia, thymoma, chronic lymphocytic leukemia, and non-Hodgkin's lymphoma. Review of bone marrow findings in 40 patients showed absence of erythroid precursors in 14 patients and rare pronormoblasts in 26. None had morphologic evidence of myelodysplasia. T-cell receptor gene rearrangement studies with Southern blot technique in 14 patients showed clonal rearrangements in nine. Karyotypic analyses performed in 28 patients showed clonal abnormalities in four. Overall, 28 of 47 patients (60%) responded to immunosuppressive therapy, but none were the patients with cytogenetic abnormalities. There was a trend toward superior response to immunosuppressive agents in the patients with T-cell LGL leukemia. Cyclophosphamide, with or without corticosteroids, was the most useful treatment agent. Cyclosporine A was effective for refractory disease. Neither the presence of an associated clinical disorder nor the existence of detectable erythroid precursors affected overall survival. We conclude that (1) T-cell LGL leukemia is the disorder most commonly associated with pure red cell aplasia, (2) the presence of clonal cytogenetic abnormality predicts poor response to immunosuppressive therapy, and (3) oral cyclophosphamide and cyclosporine A are effective treatment regimens.

Adult↗
PubMed1996

Natural leukocyte interferon-alpha therapy in patients with chronic granulocytic leukemia who have antibody-mediated resistance to treatment with recombinant interferon-alpha.

Two patients with chronic-phase chronic granulocytic leukemia initially responded to recombinant interferon alpha-2a (rIFN-alpha-2a) but relapsed as a result of development of hightiter neutralizing antibodies to rIFN-alpha-2a. Both patients were subsequently treated with natural leukocyte IFN-alpha (IFN-alpha-n3), and one of the two patients achieved a durable second hematologic and cytogenetic remission. IFN-alpha-n3 may be considered for patients in whom antibody-mediated resistance to rIFN-alpha-2a develops.

Aged↗
PubMed1996

Measurement of blood volume and red cell mass: re-examination of 51Cr and 125I methods.

Comparison of results of red cell mass (RCM) measurement by 51Cr and 125I methods in 119 patients showed virtual equivalence. Both methods have an acceptable coefficient of variation (CV) that is < 5%. The 125I method is simpler and much less expensive. Unrealistically narrow "normal ranges" for RCM are likely to lead to misdiagnosis of polycythemia vera. Upper normal limits of 39 mL/kg (males) and 32 mL/kg (females) are consistent with originally published data in normal persons; use of these limits as criteria would reduce the risk of misdiagnosis. No cases of "stress erythrocytosis" or Gaisbock Syndrome were encountered among the 119 cases reviewed.

Blood Volume↗
PubMed1996

Cyclosporine A alleviates severe anaemia associated with refractory large granular lymphocytic leukaemia and chronic natural killer cell lymphocytosis.

Large granular lymphocytic (LGL) leukaemia and chronic natural killer cell lymphocytosis (CNKL) are chronic indolent disorders often associated with neutropenia and constitutional symptoms. Severe anaemia occurs in about 20% of patients and is currently treated with corticosteroids followed by oral cyclophosphamide in non-responders. 30% of patients fail initial measures, and salvage therapy is inadequate. We describe three transfusion-dependent patients (two with T-LGL leukaemia, one with CNKL) refractory to corticosteroids, cyclophosphamide, and in one case fludarabine. Cyclosporine A (CSA) initiation resulted in prompt transfusion-independence and was well tolerated in all patients, making it an attractive alternative therapy for this disorder.

Aged↗
PubMed1996

Heterogeneity and clinical relevance of the intensity of CD20 and immunoglobulin light-chain expression in B-cell chronic lymphocytic leukemia.

In a prospective study, peripheral lymphocytes of 93 previously untreated patients with B-cell chronic lymphocytic leukemia (B-CLL) were evaluated with flow cytometry for the intensity of CD20 and surface immunoglobulin (sIg) light-chain (LC) expression. Molecules of equivalent soluble fluorescence were used to classify intensity of surface antigen expression as "strong," "moderate," or "weak." Despite reproducible morphological consistency with B-CLL, variability in intensity of CD20 and sIg light chain expression was substantial. CD20 intensity was classified as weak in 62% of patients, moderate in 12%, and strong in 26%. Expression of sIg light chain was weak in 76% and strong in 24%. The patients were followed up for a median of 3.1 years. Intensity of expression of CD20 and sIg light chain was not correlated with any presenting feature at the time of phenotyping, including clinical stage and degree of lymphocytosis or organomegaly. Similarly, clinical course of the disease, time to progression, response to therapy, and overall and treatment-free survival were not predictable from the intensity of CD20 or sIg light chain expression. In conclusion, bright expression of CD20 or sIg light chain is not an unusual feature in B-CLL and may not influence clinical presentation or short-term prognosis.

Adult↗
PubMed1996

Chronic natural killer cell lymphocytosis.

Chronic proliferations of natural killer (NK) cells (CD3- CD16+) are identified initially by detecting large granular lymphocyte (LGL) excess in a peripheral blood smear and subsequent lymphocyte immunophenotyping by flow cytometry. A related disease, T-LGL leukemia, has an indolent clinical course with chronic neutropenia and a close association with rheumatoid arthritis. Herein are described the clinical presentation and long-term clinical course of patients with chronic NK cell lymphocytosis (CNKL). The majority of the 14 patients followed up for a median of 4 years presented with severe cytopenias or vasculitic syndromes that were responsive to immunosuppressive therapy. Other manifestations included fever and arthralgias. In general, the disease was nonprogressive and had a course similar to that of T-LGL leukemia.

Adult↗
PubMed1996

Current perspective in agnogenic myeloid metaplasia.

Agnogenic myeloid metaplasia (AMM) carries the worst prognosis among the chronic myeloproliferative disorders. Substantial bone marrow fibrosis, extramedullary hematopoiesis, anemia and hepatosplenomegaly are the characteristic features of the disease. AMM is currently incurable and the available treatment agents are mostly palliative and do not prolong life. Two pathogenetic processes are responsible for the impaired hematopoiesis and the clinical manifestations. The primary disease process is a clonal hematopoietic stem cell disorder which results in chronic myeloproliferation and atypical megakaryocytic hyperplasia. The secondary process of bone marrow fibrosis is the result of non-clonal fibroblastic proliferation and hyperactivity induced by growth factors abnormally shed from clonal megakaryocytes. Therefore, experimental treatment strategies may be directed towards either one or both of these disease processes. This report summarizes the current management options and new therapeutic endeavours.

Bone Marrow Examination↗
PubMed1996

Spectrum of diseases associated with increased proportions or absolute numbers of peripheral blood natural killer cells.

In a retrospective review of 1501 lymphoid flow cytometric studies of peripheral blood, we identified an increased proportion of natural killer cells in 125 cases (8%), 49 (3%) of which had a concomitant increase in absolute number of natural killer cells. Of the latter, the most frequent associated disorder was chronic natural killer cell lymphocytosis. Substantial quantitative increases in natural killer cells were also observed in some patients with lymphoma, leukaemia, immune thrombocytopenic purpura, or myelodysplastic syndrome. Our study provides incidence figures and clinical associations of an increased number of natural killer cells in the peripheral blood.

Flow Cytometry↗