Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Population-based case-control interview studies of white men, 578 with leukemia, 622 with non-Hodgkin's lymphoma, and 820 controls from Iowa and Minnesota and 173 with multiple myeloma and 452 controls from Iowa, offered the opportunity to investigate the relationship of these cancers with alcohol consumption. Although drinkers had non-significantly elevated risks for specific subtypes of leukemia (acute lymphocytic leukemia (OR = 3.0), myelodysplasia (OR = 1.6), and other leukemia (OR = 1.5)) and multiple myeloma (OR = 1.3), there were no statistically significant findings and no dose-response gradients with amount of alcohol consumed. Thus, these data suggest that alcohol is not an important contributor to the etiology of lymphatic and hematopoietic tumors.
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PMID:Alcohol consumption and risk of leukemia, non-Hodgkin's lymphoma, and multiple myeloma. 140 12

This report describes the efficacy and toxicity of PAVe (procarbazine, Alkeran, vinblastine) and irradiation (RT) in the management of 159 patients with locally extensive or advanced stage Hodgkin's disease (HD) at Stanford University. Patients received six courses of chemotherapy alternating with RT. The extent of RT and the schedule of treatment varied according to the stage of disease. About 2/3 of patients received PAVe/RT in the setting of prospective, randomized clinical trials. The rate of complete response was 93%. With a median follow-up of seven years (range 2-17), the 15 year actuarial freedom from progression (FFP) is 78% and overall survival is 75%. Ten-year FFP by stage is: 80% for locally extensive stage II, 90% for stage IIIA and 70% for stage IIIB. Excellent and equal results were attained with PAVe/RT vs. MOP(P) (mustard, Oncovin, procarbazine with or without prednisone)/RT in the randomized combined modality studies. Progression or recurrence was documented in 30 patients and was more common in irradiated sites. PAVe was well tolerated acutely. There were no treatment related fatalities. Twenty-three (14%) patients were admitted to the hospital for neutropenic fever. Five second malignancies have occurred after PAVe/RT only: one myelodysplastic syndrome, one acute myelogenous leukemia, one non-Hodgkin's lymphoma and two solid tumors including a case of non-small cell lung cancer and an in situ carcinoma of the cervix. Three patients died from myocardial infarction several years after the completion of treatment. These mature data show that PAVe/RT is effective and well-tolerated therapy for locally extensive stage II and IIIA/B HD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The Stanford experience with combined procarbazine, Alkeran and vinblastine (PAVe) and radiotherapy for locally extensive and advanced stage Hodgkin's disease. 145 64

Expression of the normally cryptic blood group antigen Tn has occasionally been reported in hematologic disease, but the true frequency of this change is not known. A mouse monoclonal antibody (FBT3) and immunohistochemistry were used to examine expression of the Tn antigen. Expression was not detected in 35 normal bone marrow aspirates examined, but it was detected in 5 of 725 abnormal bone marrow aspirates, including 2 (3.6%) of 55 cases of de novo acute nonlymphocytic leukemia and 2 cases that terminated in acute nonlymphocytic leukemia. In two patients, one with acute myeloblastic leukemia and the other in blast transformation of chronic myeloid leukemia, the Tn antigen was expressed on 2 percent of blast cells. In one case of non-Hodgkin's lymphoma, 4 percent of normal myeloid cells expressed the antigen. In the other two cases, one of acute myelomonocytic leukemia and the other of myelodysplasia, only 2 to 8 percent of myeloid and erythroid cells initially were Tn positive. Subsequent serial immunohistochemical studies of bone marrow aspirates and peripheral blood in these two cases showed increasing numbers of Tn-positive erythroid and myeloid cells 8 to 12 months before polyagglutination was detected serologically. Tn-positive cells increased to > 90 percent in the terminal phase in both cases of both diseases. The results suggest that Tn expression in these two patients may have conferred a growth advantage to the cells and could be related to disease progression.
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PMID:Expression of the Tn antigen in myelodysplasia, lymphoma, and leukemia. 147 Dec 47

Twenty-one patients with a median age of 9 years (0.5-19) underwent intensified myeloblative therapy: 1800 mg/m2 etoposide (VP) was added to 120 mg/kg cyclophosphamide (CY) and 12 Gy fractionated total body irradiation (FTBI) or 12-16 mg/kg busulfan (BU) for treatment of acute lymphoblastic leukemia (11 patients), acute myeloid leukemia (8 patients), non-Hodgkin's lymphoma (1 patient), or myelodysplastic syndrome (1 patient). Severe liver toxicity occurred in 5 of 7 children (71%) receiving short-term methotrexate (MTX) and additional cyclosporin A (CSA) for prophylaxis of graft-versus-host disease (GVHD). Three of them died of subsequent acute renal failure on days 8, 13, and 34. In contrast, acute severe organ toxicity occurred in only 1 of 14 children (7%) receiving the same intensified regimens who were autografted (7 pts) or received MTX alone for GVHD prophylaxis (7 pts). These observations suggest that GVHD prophylaxis with MTX and CSA may adversely influence the tolerance of intensified antileukemic regimens in children.
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PMID:Limited tolerance of intensified conditioning regimens in children receiving methotrexate/cyclosporin A for graft-versus-host disease prophylaxis. 155 71

Hematologic manifestations of human immunodeficiency virus (HIV) infection include cytopenias, non-Hodgkin's lymphoma, and myelodysplasia. Acute lymphocytic leukemia has rarely been reported in association with HIV infection. We describe a patient who presented with Burkitt cell leukemia and myelodysplasia as her initial manifestation of HIV infection. The dysplastic features included circulating asymmetric binucleated red blood cells as well as pseudo Pelger-Huet cells. To the best of our knowledge, this has not been previously reported.
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PMID:Burkitt cell leukemia with myelodysplasia as a presentation of HIV infection. 160 45

We report on four cases of trisomy 14 as the sole anomaly. Three cases were myelodysplastic syndromes and one was a non-Hodgkin's lymphoma. This anomaly is mainly in myeloid disorders and still remains to be well documented. On the other hand, we show this anomaly to be also a non-random anomaly in lymphoproliferative disorders.
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PMID:Four additional cases of trisomy 14 as the sole anomaly in various haematological malignancies. 162 80

The frequency of chromosome aberrations in the peripheral blood of patients successfully treated for Hodgkin's disease (HD) and non-Hodgkin's lymphoma is compared with that seen in age-matched haematologically normal subjects. Findings are considered in relation to risk factors associated with the development of secondary myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML). Overall aberration frequencies were not significantly increased in patients compared with normal subjects. However, there were differences in aberration type. The frequency of exchanges was significantly higher among patients (P less than 0.01) and the frequency of gaps lower (P less than 0.0005). The mean frequency of exchanges was also greater in patients receiving multiple compared to single courses of therapy (P less than 0.0005) and in patients receiving radiotherapy or combined modality therapy compared to chemotherapy alone (P less than 0.005 and P less than 0.0005). Four patients had aberration frequencies greater than 2 SD above the patient mean. One of these was also found to have a mutation of the ras oncogene. None of the patients has yet developed secondary MDS/AML.
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PMID:Chromosome aberrations following cytotoxic therapy in patients in complete remission from lymphoma. 163 73

In this study, we investigated a possible association between the degree of macrophage activation - as measured by serum neopterin concentrations - and disturbances of iron metabolism, determined by the concentrations of ferritin and serum iron, in patients with malignant disorders. Additionally we evaluated correlations between these factors and the degree and type of anaemia. Seventy-three patients, who suffered from non-Hodgkin's lymphoma (NHL) (n = 43), Hodgkin's disease (n = 11), myeloma or monoclonal gammopathy of unknown significance (n = 9), myelodysplastic syndrome (n = 1), and solid tumours (n = 9), were examined. Mean neopterin levels were raised in all groups, patients with NHL showing the highest concentrations. Ferritin but not neopterin concentrations were higher in males than in females. A significant correlation was found between neopterin and ferritin concentrations (p less than 0.01). Considering only female patients the strength of the correlation was the same (p less than 0.02). In addition, we found inverse correlations of neopterin with haemoglobin and iron concentrations (all p less than 0.01). Similar relationships existed in patients during follow-up. Our results support the hypothesis of an association between the degree of activation of macrophages and the development of anaemia by a shift or iron towards the storage sites.
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PMID:Association between the activation of macrophages, changes of iron metabolism and the degree of anaemia in patients with malignant disorders. 164 56

Relapse continues to be a problem after bone marrow transplantation (BMT) for hematologic malignancies, particularly in recipients of autologous or T-cell-depleted allogeneic grafts and in patients with advanced disease. Interferon (IFN) has shown antiproliferative activity in several malignant hematologic diseases and potentially may be of benefit when administered early after BMT when the number of residual cells is minimal. We tested in a phase I study the maximum tolerated daily dose of recombinant IFN alpha-2b in patients who had received a transplant for a disease at high risk for relapse (acute myeloid leukemia or non-Hodgkin's lymphoma beyond first remission, advanced myelodysplastic syndrome, acute lymphoblastic leukemia at any stage, chronic myeloid leukemia in accelerated or blast phase. Recombinant IFN alpha-2b was started at a dose of 0.5 x 10(6) IU/m2 and escalated by 0.5 x 10(6) IU/m2 in groups of three or four patients. The intention was to administer IFN as soon as stable engraftment after BMT was achieved (defined as an absolute neutrophil count of greater than 2.0 x 10(9)/L and platelet count greater than 100 x 10(9)/L for 5 consecutive days) and continued for 2 months. A total of 14 patients were enrolled after autologous (n = 3) or allogeneic (n = 11) BMT. Dose-limiting toxicity was myelosuppression. Significant (grade 2 to 4) neutropenia and thrombocytopenia led to discontinuation or dose reduction in five of eight patients receiving 1.5 x 10(6) or 2 x 10(6) IU/m2 IFN. Mild to moderate (grade 1 or 2) anorexia, weight loss, and fatigue occurred in the majority of patients independent of the IFN dose. De novo acute GVHD responsive to steroid treatment developed in 3 of 11 allograft recipients. Natural killer (NK) cell function was low before IFN treatment and was not improved with the cytokine. Conversely, interleukin-2-activated NK cells showed normal function even before starting IFN and no change was seen during IFN treatment. Clonogenic hematopoietic progenitor studies showed depression of all progenitor lines (colony-forming unit [CFU]-granulocyte, erythroid, monocyte, megakaryocyte, CFU granulocyte-macrophage, burst-forming unit-erythroid) by IFN at all dose levels except at 0.5 x 10(6) IU/m2. Considering this result and the incidence and severity of marrow depression seen at doses greater than 1.0 x 10(6) IU/m2, we would consider this the maximum dose safely tolerated if IFN alpha-2b is administered in this setting for a prolonged course on a daily basis.
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PMID:Treatment with recombinant interferon (alpha-2b) early after bone marrow transplantation in patients at high risk for relapse [corrected]. 174 91

The activity of microsomal HMG-CoA reductase in freshly isolated leukocytes from patients with a variety of hematologic malignancies was significantly increased (up to 20-fold) when compared to enzyme activity in leukocytes from normal subjects (average 10.3 +/- 0.8 pmol/min per mg). Increased enzyme activity was not due to nonspecific leukocyte stimulation or to the presence of a malignancy, since normal enzyme activity was observed in subjects with either viral illnesses or solid tumors. Increased HMG-CoA reductase activity accompanying hematologic malignancy could also not be attributed to alterations in enzyme-substrate kinetic parameters (Km), or to alterations in the phosphorylation state or thiol-disulfide status of the enzyme, nor was it correlated with differences in serum lipid or lipoprotein concentrations. The increase (3.6-fold) in HMG-CoA reductase activity in leukocytes from patients with preleukemia was due entirely to a rise in enzyme catalytic efficiency (specific activity), whereas the increase (4.3-fold) observed in leukocytes from patients with overt leukemia or non-Hodgkin's lymphoma was due to a concomitant increase in both enzyme catalytic efficiency (2.5-fold) and enzyme protein concentration (1.6-fold). Similar increases in HMG-CoA reductase activity and catalytic efficiency were also noted for both transformed, nonmalignant, and malignant cultured leukocytes, suggesting that increased enzyme catalytic efficiency is not a nonspecific consequence of physiological changes occurring in response to the malignancy but may be an integral aspect of the malignant phenotype. HMG-CoA reductase protein concentrations, however, were not elevated in either transformed, nonmalignant, or malignant cultured leukocytes, suggesting that increases in enzyme protein levels may be secondary to other physiological changes that occur during the development of overt leukemia. Taken together, these observations suggest that an increase in the activity of HMG-CoA reductase, the rate-controlling enzyme in cholesterol synthesis, is a common occurrence in human hematologic malignancies and that a biphasic elevation of enzyme activity may exist in malignant leukocytes, such that changes in catalytic activity may occur early in tumorigenesis and may be followed by secondary changes in enzyme levels.
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PMID:In vivo regulation of human leukocyte 3-hydroxy-3-methylglutaryl coenzyme A reductase: increased enzyme protein concentration and catalytic efficiency in human leukemia and lymphoma. 177 Mar 7


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