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Biomedical subjects

A Tefferi

Publications and source records attributed to A Tefferi.

At least 127 records · Page 7Linked to original sources
PubMed1998

Anemia after orchiectomy.

The decrease in testosterone production associated with bilateral orchiectomy may result in normocytic anemia in men. We sought to determine the effect of orchiectomy on hemoglobin concentration. Patients were evaluated at the Mayo Clinic in 1993 and 1994 and underwent bilateral orchiectomy for prostate carcinoma. All patients were seen by one of the staff urologists. Patients were included if they had a normal preoperative complete blood cell count and serum levels of creatinine, if they remained without disease progression (suppressed prostate-specific antigen level and no evidence of clinical progression on review), and if they had normal serum levels of creatinine and mean corpuscular volume during the follow-up period. The patients could have no other cause of anemia. The complete blood cell count, prostate-specific antigen level, and serum level of creatinine were determined preoperatively and at least once (>90 days) after orchiectomy. Sixty-four patients were included in the analysis (median age, 68 years). The median decrease in hemoglobin concentration was 1.2 g/dL after orchiectomy. There was a statistically significant difference in the hemoglobin concentration before orchiectomy compared with postoperative values at all the intervals studied, both by the paired group t-test and the Kruskal-Wallis test. There is a clinically and statistically significant decrease in hemoglobin concentration after orchiectomy. Knowledge of this phenomenon may prevent unnecessary diagnostic work-up in men with normocytic anemia after bilateral orchiectomy.

Aged↗
PubMed1998

Treatment of polycythaemia vera and essential thrombocythaemia.

The clinical course in both polycythaemia vera (PV) and essential thrombocythaemia (ET) is characterized by significant thrombohaemorrhagic complications and variable risk of disease transformation into myeloid metaplasia with myelofibrosis or acute myeloid leukaemia. Randomized studies have shown that the risk of thrombosis was significantly reduced in ET with the use of hydroxyurea (HU) and in PV with the use of chlorambucil or 32P. However, the use of chlorambucil or 32P has been associated with an increased risk of leukaemic transformation. Subsequently, other studies have suggested that both HU and pipobroman may be less leukaemogenic and as effective as chlorambucil and 32P for preventing thrombosis in PV. However, the results from these prospective studies have raised concern that even HU and pipobroman may be associated with excess leukaemic events in both ET and PV. The recent introduction of anagrelide as a specific platelet-lowering agent, the demonstration of treatment efficacy with interferon-alpha, and the revived interest in using low-dose acetylsalicylic acid provide the opportunity to initiate prospective randomized studies incorporating these treatments.

Adult↗
PubMed1998

Late-onset noninfectious pulmonary complications after allogeneic bone marrow transplantation.

We examined the incidence and clinical outcome of late-onset noninfectious pulmonary complications (LONIPC) in a series of 234 patients who underwent allogeneic bone marrow transplantation at our institution between April 1982 and October 1996. The 179 patients who survived 3 months or more were evaluated. Clinical, radiologic, pulmonary function, and pathologic tests were reviewed to identify 18 patients (10%) who fulfilled the diagnostic criteria of LONIPC. Accordingly, the pulmonary processes included bronchiolitis obliterans (BO, five patients), bronchiolitis obliterans with organizing pneumonia (BOOP, three patients), diffuse alveolar damage (DAD, one patient), lymphocytic interstitial pneumonia (LIP, one patient), and nonclassifiable interstitial pneumonia (NCIP, eight patients). Various methods of enhanced immunosuppressive therapy resulted in marked durable remission in nine patients (50%) (3/3 with BOOP, 3/8 with NCIP, 1/1 with DAD, 1/1 with LIP, 1/5 with BO). The presence of chronic graft-versus-host disease (cGVHD) and prophylaxis for GVHD with cyclosporine and prednisone were the only variables significantly associated with the development of LONIPC (P = 0.0001 and 0.008, respectively). Regardless of histology, a reduction in the forced expiratory volume to < 45% of the predicted range was associated with poor response to treatment. These findings suggest a strong association between cGVHD and LONIPC and that the risk of LONIPC development may be influenced by the particular method of GVHD prophylaxis. Most patients with BOOP or mild airflow limitation at diagnosis achieved durable remissions.

Adolescent↗
PubMed1998

Splenic irradiation for symptomatic splenomegaly associated with myelofibrosis with myeloid metaplasia.

Twenty-three patients who had myelofibrosis with myeloid metaplasia (MMM) were treated at our institution with 50 courses of splenic irradiation (SI) for symptomatic splenomegaly. The median dose of radiation per course was 277.5 cGy, administered in a median of 7.5 fractions. 8/23 patients received multiple courses of SI. Of 49 evaluable courses of SI, 46 (93.9%) resulted in an objective decrease in spleen size. The median duration of response was 6 months (range 1-41). Reduction in spleen size was associated with symptomatic relief in all patients. Overall median survival after SI was 22 months. Significant cytopenia occurred in 10 (43.5%) patients, or 16 (32%) of the 50 courses of SI. Prolonged, life-threatening pancytopenia after a single course of SI occurred in six patients (26%), resulting in fatal sepsis or haemorrhage in three (13%). Nine patients underwent subsequent splenectomy: the perioperative mortality rate was 11%. One third of patients experienced postoperative intra-abdominal haemorrhage necessitating surgical re-exploration. SI can provide symptomatic relief and a reduction in spleen size in most MMM patients. The increased risk of postoperative bleeding in patients requiring subsequent splenectomy dictates against considering SI as an alternative to splenectomy for patients who are otherwise good surgical candidates.

Adult↗
PubMed1998

Treatment of acute myelogenous leukemia in the older patient with attenuated high-dose ara-C.

We have evaluated the activity and toxicity of cytosine arabinoside (ara-C; 750 mg/m2 intravenously given over 3 hours every 12 hours for 12 doses) to induce remission in older (median age, 73 years) newly diagnosed patients who had acute myelogenous leukemia (AML). A maximum of two cycles of induction were administered. Patients who achieved complete remission could receive three additional consolidation courses limited to 4 to 6 doses of ara-C every 12 hours, depending on marrow cellularity. Thirty patients were evaluable. Twenty-two patients had one or more unfavorable prognostic factors, including antecedent hematologic disorders (10), cytogenetic abnormalities (17), or hyperleucocytosis (5). Fourteen patients (47%) achieved complete remission. Four patients did not receive consolidation as planned because of medical contraindication or refusal, and three patients relapsed during consolidation. The median duration of complete remission was 326 days. Sixteen patients failed induction because of relative or absolute drug resistance in nine patients, or death in seven patients. Median survival for the entire group was 6 months. Toxicity was significant, with a median initial hospitalization of 29 days. These results are comparable to those reported in the literature and suggest that this regimen may be considered to be an alternative to an anthracycline-containing regimen.

Aged↗
PubMed1998

The Philadelphia chromosome negative chronic myeloproliferative disorders: a practical overview.

The chronic myeloid disorders are collectively characterized by a stem cell origin of the clonal process and a variable tendency to undergo indigenous disease transformation and leukemic conversion. Classification of the chronic myeloid processes is based primarily on the presence or absence of the Philadelphia chromosome (bcr-abl translocation) and secondarily on the morphologic picture of the bone marrow in conjunction with the clinical manifestation. Essential thrombocythemia (ET), polycythemia vera (PV), and agnogenic myeloid metaplasia (AMM) constitute the classical group of bcr-abl negative chronic myeloproliferative disorders. PV is characterized by a clonal increase in red blood cell mass, AMM by bone marrow fibrosis, and ET by thrombocytosis. Most of these features, however, are not diagnostically specific, and secondary causes of erythrocytosis, thrombocytosis, and bone marrow fibrosis must be excluded. Treatment may be deferred or limited to phlebotomy alone in some patients with ET or PV, respectively. In contrast, thrombosisprone patients with PV or ET require drug therapy, and new platelet-lowering agents are increasingly being used. In this article, current diagnostic and therapeutic issues of ET, PV, and AMM are discussed.

Chronic Disease↗
PubMed1997

Bone marrow granulomas associated with chronic natural killer cell lymphocytosis.

Two patients with chronic natural killer cell lymphocytosis (CNKL) and associated bone marrow granulomas (BMGs) are described. The increases in the peripheral blood of both the proportion (64 and 74%) and absolute number (2,000/microL and 4,700/microL) of NK cells have persisted for more than 1 and 3 years. One patient was asymptomatic with thrombocytopenia and neutropenia, and the other presented with fever of unidentified origin, which has since responded to a nonsteroidal anti-inflammatory agent. Bone marrow examination in both patients showed loose aggregates of epithelioid histiocytes similar to the noncaseating granulomas seen in other diseases. An unusual feature, however, was the presence of many scattered, large mononuclear histiocytes that were morphologically similar to atypical megakaryocytes. Extensive clinical and laboratory studies did not reveal an established cause for the BMGs. BMGs may be associated with CNKL, with the unusual feature of scattered, atypical mononuclear histiocytes.

Aged↗
PubMed1997

Follicular dendritic cell sarcoma mimicking diffuse large cell lymphoma: a case report.

Follicular dendritic cell sarcomas (FDCSs) are rare tumors arising from follicular dendritic cells in lymphoid tissue. Fewer than 20 cases have been described in the English-language literature. We describe the second case of an FDCS with primary liver involvement. The initial diagnosis was lymphoma, and appropriate treatment was prescribed. After the initial treatment failed, additional biopsy samples were obtained. Standard pathologic analysis and immunophenotyping for a panel of monoclonal antibodies were performed on formalin-fixed paraffin-embedded tissue and frozen sections. The pathologic findings were consistent with FDCS, and the specimens showed some of the characteristic pathologic features suggestive of this tumor, including multinucleation and a spindle pleomorphic morphology. The tumor cells were positive for S-100 protein, CD45, CD14, and vimentin. Because of its morphological characteristics, FDCS can be confused with other neoplastic entities, such as lymphomas and other solid tumors.

Antigens, CD↗
PubMed1997

Acquired von Willebrand disease: concise review of occurrence, diagnosis, pathogenesis, and treatment.

Acquired von Willebrand disease (AvWD) is a rare complication of an autoimmune or neoplastic disease. It is associated mostly with a lymphoid or plasma cell proliferative disorder. The clinical manifestations are similar to congenital von Willebrand disease. Diagnosis is confirmed by the demonstration of decreased levels of factor VIII coagulant activity (VIII:C), ristocetin cofactor activity (vWF:RCo), and von Willebrand factor (vWF) antigen (vWF:Ag). vWF multimer analysis usually reveals a type II defect with decreased abundance of higher molecular weight vWF multimers. Various pathogenetic mechanisms have been described, including the development of anti-vWF antibodies and adsorption of vWF by tumor cells. Successful management approaches have included treatment of the underlying disorder, infusion of high-dose gamma globulin, replacement therapy with factor VIII/vWF concentrates, intravenous infusion of desmopressin, and administration of corticosteroids.

Diagnosis, Differential↗
PubMed1997

Clinical correlations of immunophenotypic variations and the presence of trisomy 12 in B-cell chronic lymphocytic leukemia.

In a prospective study of 93 consecutive untreated patients with B-cell chronic lymphocytic leukemia, we examined the clinical relevance of surface immunoglobulin (sIg) heavy chain (HC) and light chain (LC) isotypes, CD11c or CD25 expression, and the presence of trisomy 12 by fluorescence in situ hybridization (FISH). Careful morphologic evaluation was performed to exclude patients with other forms of chronic lymphoid leukemias, including mantle cell lymphoma, prolymphocytic leukemia, and leukemia phase of lymphoma. In addition, clonally restricted sIg and CD5 surface determinant were expressed in all patients. Clinical presentation, including blood cell counts, clinical stage, and organomegaly, did not correlate with any of the measured variables. After a median follow-up period of 3 years, the particular HC or LC isotype or CD11c expression did not correlate with either disease progression or treatment-free survival. However, trisomy 12 and CD25 expressions were both associated with accelerated disease progression and a shorter treatment-free survival time. Our results confirm the adverse prognostic significance of trisomy 12 expression in chronic lymphocytic leukemia and suggest that CD25 expression may have an unfavorable clinical impact.

Adult↗
PubMed1997

Cytogenetic and molecular genetic methods for diagnosis and treatment response in chronic granulocytic leukemia.

Today, laboratory geneticists help clinical hematologists diagnose chronic granulocytic leukemia (CGL) and monitor the response of patients undergoing treatment. The most common genetic tests for CGL include quantitative cytogenetic studies, fluorescence in situ hybridization with probes for BCR and ABL, Southern blot analysis, and reverse transcriptase polymerase chain reaction. No single genetic testing procedure fulfills all the needs of clinicians who care for patients who have CGL. Thus, it has become important to use combinations of testing methods that are both accurate and cost-effective for any given clinical situation in the diagnosis and treatment of patients with CGL.

Antineoplastic Agents↗
PubMed1997

New drugs in essential thrombocythemia and polycythemia vera.

Among the chronic myeloproliferative disorders, polycythemia vera and essential thrombocythemia are unique because of their association with thrombohemorrhagic manifestations and their relatively indolent clinical course. Patients with essential thrombocythemia may not have a significant shortening of life-expectancy and most may not require specific therapy. However, patients with polycythemia vera have a significant risk of transformation of polycythemia vera into acute leukemia or postpolycythemic myelofibrosis (or both). 'High-risk-for-thrombosis' patients with either polycythemia vera or essential thrombocythemia require specific therapy with a platelet-lowering agent to prevent thrombotic complications. Currently, the standard agent used for this is hydroxyurea. However, its tetratogenic and leukemogenic potential has been of concern. As a result, new platelet-lowering agents are being evaluated in the treatment of polycythemia vera and essential thrombocythemia. Anagrelide and interferon alfa are two such agents and have been shown to be effective in reducing platelet counts in patients with chronic myeloproliferative disorders. The putative mechanism of action of these drugs, their specific activity in polycythemia vera and essential thrombocythemia, side-effect profile, and current indications are discussed herein.

Antineoplastic Agents↗
PubMed1997

Factors influencing platelet recovery after blood cell transplantation in multiple myeloma.

We sought to determine factors that impact on the recovery of platelets after blood cell transplantation in patients with multiple myeloma. We performed retrospective analyses in 51 patients undergoing blood cell transplantation for multiple myeloma. The proportional-hazards model was applied to determine significant risk factors. Of 51 transplants, 14 patients failed to achieve a platelet count of 50 x 10(9)/l. Median time to a neutrophil count of 0.5 x 10(9)/l was 10.5 days. Median time to achieve a platelet count of 50 x 10(9)/l was 32 days. Multivariate analysis revealed that cyclophosphamide and G-CSF priming before collection of hematopoietic precursors (P < 0.001) was a positive predictor of rapid engraftment and prior exposure to melphalan given orally (P = 0.02) was a negative predictor of subsequent platelet engraftment. The number of mononuclear cells collected, the patient's disease status at the time of transplant and the presence of circulating plasma cells in the harvested product did not have a significant impact on time to platelet engraftment. We conclude that cyclophosphamide and G-CSF priming shortened the time to achieve platelet engraftment compared with G-CSF alone. Prior exposure to melphalan delayed platelet engraftment and can lead to complete failure of platelet recovery. Stem cells should be collected before melphalan administration in patients with multiple myeloma who are candidates for possible blood cell transplantation.

Adult↗
PubMed1997

Spontaneous pneumomediastinum in a patient with bronchiolitis obliterans after bone marrow transplantation.

After allogeneic bone marrow transplantation for chronic myelogenous leukemia, spontaneous pneumomediastinum and subcutaneous emphysema developed in a patient with bronchiolitis obliterans. Computed tomography scanning of the chest failed to reveal the cause. There was no evidence of a pulmonary process, pneumothorax, or pharyngeal or upper airway leak. Despite the alarming appearance of the patient, conservative management, including high-flow oxygen, resulted in resolution of the pneumomediastinum and subcutaneous emphysema. The cause of pneumomediastinum and subcutaneous emphysema in bone marrow transplant recipients is discussed.

Bone Marrow Transplantation↗
PubMed1997

The effects of anagrelide on human megakaryocytopoiesis.

Anagrelide, an inhibitor of platelet aggregation, decreases the number of platelets in normal subjects and in patients with myeloproliferative disorders. We describe studies aimed at discovering the general mechanism(s) by which anagrelide acts. We examined three hypotheses: (1) anagrelide shortens platelet survival, (2) anagrelide inhibits the proliferation of megakaryocytic-committed progenitor cells (CFU-M), and (3) anagrelide inhibits maturation of megakaryocytes. We observed that anagrelide did not shorten platelet survival. Proliferation of CFU-M in vivo was not affected by anagrelide, although high concentrations of anagrelide inhibited CFU-M in vitro. In-vivo and in-vitro anagrelide altered the maturation of megakaryocytes, causing a decrease in their size and changing other morphometric features. We conclude that anagrelide decreases the number of platelets primarily by interfering with the maturation of megakaryocytes.

Adult↗
PubMed1997

2-Chlorodeoxyadenosine treatment after splenectomy in patients who have myelofibrosis with myeloid metaplasia.

2-Chlorodeoxyadenosine (2-CdA) is a purine nucleoside analogue with therapeutic activity in low-grade lymphoproliferative disorders. In addition, 2-CdA has a potent myelosuppressive effect, and it has been shown to be toxic to malignant myeloid cells both in vitro and in vivo. In this pilot study we treated nine patients who had advanced myelofibrosis with myeloid metaplasia (MMM) and progressive hepatomegaly or symptomatic thrombocytosis after therapeutic splenectomy. 2-CdA was administered at 0.05-0.1 mg/kg/d for 7 d for one to five treatment cycles. A reduction in liver size associated with marked improvement in fatigue and control of thrombocytosis and leucocytosis was achieved in seven of the nine patients (78% response rate). In four of the seven responding patients the reduction in liver size was durable (4-28 months) and was associated with a decrease in serum alkaline phosphatase levels. However, no patient had improvement in anaemia, and two of the seven initially responding patients have since died of acute leukaemia or progressive disease. Improvement in bone marrow fibrosis was noted in two of five available post-treatment marrow examinations. Toxicity was mainly myelosuppression, which was severe in two patients. 2-CdA may be considered a palliative therapeutic agent after splenectomy in noncytopenic patients with MMM who have progressive hepatomegaly or extreme thrombocytosis.

Anemia↗