Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We analyzed active oxygen (hydroperoxide; H2O2) production by peripheral neutrophils in various hematological diseases by flow cytometry. One hundred microliters of heparinized fresh blood was sequentially incubated at 37 degrees C with 2',7'-dichlorofluorescein diacetate and with or without phorbol myristate acetate (PMA). After hemolysis, the pelleted white blood cells were subjected to flow cytometry, and the neutrophil fraction was gated on the cytogram. Production of H2O2 by the fraction was estimated by determining the increase in the relative intensity of fluorescence emitted from the fraction in response to stimulation by PMA. In controlled chronic myelogenous leukemia (CML) (WBC < 1 x 10(10)/1), H2O2 production was normal, while in uncontrolled CML (WBC > or = 1 x 10(10)/1), it was reduced. In myelodysplastic syndrome (MDS), H2O2 production was also reduced, but no significant difference was observed among FAB classification disease types in MDS patients. In untreated acute non-lymphocytic leukemia (ANLL), H2O2 production was reduced, while in the complete remission stage of ANLL, its level was normal, suggesting recovery from normal clones. In aplastic anemia, the H2O2 production level was normal. Steroid therapy might be responsible for the reduction of H2O2 production in non-Hodgkin's lymphoma and multiple myeloma. The production of H2O2 is closely related to the oxygen-dependent bactericidal activity of neutrophils, and, hence, can be utilized as an index to indicate susceptibility to infection. This neutrophil function can be determined easily in ordinary clinical facilities by using flow cytometry, and care should be taken to prevent infection when H2O2 production is reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Flow cytometric determination of active oxygen (hydroperoxide) produced by peripheral blood neutrophils in patients with hematological disorders. 836 85

At least 60 case studies of leukemia among people exposed to chronic low-dose alpha-particle radiation from injections with the radiographic contrast medium Thorotrast and 115 cases from follow-up studies have been described in the literature. In the present study, malignant hematological diseases among 1003 Danish patients injected during 1935-1947 and followed to 1992 accruing 20,433 person-years were assessed and available histopathological specimens revised. The mean cumulative bone marrow alpha-particle radiation dose (1.34 Gy) was estimated from records of the amount of Thorotrast injected (mean 18.7 ml). Sixteen cases of acute myelogenous leukemia (AML) and seven cases of myelodysplastic syndrome (MDS) were diagnosed 8-40 years after injection, the cumulative frequency reaching 7.6%. No significant relationship was seen between the cumulative frequency of AML + MDS and the age at injection, gender, or amount of Thorotrast injected, but a multivariate analysis described data best by a model with the bone marrow dose and the power of the attained age. The risk estimate for AML + MDS was 173 cases/10(4) persons per Gy. If also considering cases of acute lymphocytic leukemia (1), chronic myelogenous leukemia (3), non-Hodgkins lymphoma (4), and multiple myeloma (2), the risk estimate became 248 cases/10(4) persons per Gy. It is suggested that RBE of alpha particles from thorium may be lower than 20.
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PMID:Leukemia and other related hematological disorders among Danish patients exposed to Thorotrast. 824 91

Allogeneic bone marrow transplantation has an established role in the treatment of malignant blood diseases. For some disorders it is at the moment the only curative treatment. As the complication risks of this treatment increase with age, the upper age limit for allogeneic transplantation is usually 50 to 60 years. The main indications are acute leukaemias, chronic myeloid leukaemia and myelodysplastic syndromes. Selected patients with chronic lymphatic leukaemia, multiple myeloma and lymphoma are also treated with allogeneic transplantation. The most common intensive conditioning regimen preceding the transplantation consists of total body irradiation and cyclophosphamide. The source of haematopoietic stem cells has routinely been bone marrow, but the number of transplantations with stem cells harvested from blood is rapidly increasing. The proportion of transplantations from unrelated donors is growing. Histocompatibility testing is becoming more precise, which is likely to improve the results of unrelated donor transplantations to the level achieved with sibling donor transplantations.
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PMID:[Allogeneic bone marrow transplantation in malignant blood diseases]. 852 30

Generalized or localized itch without primary skin manifestations may be the presenting symptom of serious internal diseases. Five characteristic cases of pruritus are discussed: Hodgkin's disease, primary sclerosing cholangitis, polycythemia vera, iron deficiency (with pica), and uremia. Other important causes must be considered; all forms of cholestasis, including primary biliary cirrhosis, drug-induced, pregnancy-related, and extrahepatic cholestasis; other hematologic and malignant disorders such as non-Hodgkin's lymphoma, leukemia, multiple myeloma, solid tumors, and myelodysplastic syndromes; metabolic and endocrine diseases, most notably diabetes mellitus, hyperthyroidism, hypothyroidism, and carcinoid syndrome; focal neurologic diseases such as brain tumors, cerebral infarctions and multiple sclerosis; adverse drug reactions without rash; infectious diseases, especially parasitic and HIV infections. A diagnostic laboratory screening for pruritus of undetermined origin is suggested.
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PMID:[Pruritus--also a challenge in internal medicine]. 852 44

As a first step to evaluate the possibility of gene therapy using adenoviral vectors in hematological malignancies in vivo, we tested the efficacy of gene transfer by a recombinant adenovirus in cell lines and fresh cells from various hematological neoplasms. Thirteen cell lines and samples from 27 patients were studied. Cells were infected by a recombinant adenovirus expressing beta galactosidase gene (Ad RSV betagal) and efficacy of transduction assessed by evaluating betagal expression in cells with a histochemical method. After infection of the cells at a multiplicity of infection (MOI) of 200 p.f.u./cell, the percentage of beta gal-positive cells after 48h was high in two cell lines. K562 (64%) and RPMI 8226 (a myeloma cell line, 65%), relatively large in the two myeloma cell lines tested (41% and 20%, respectively) and in MT4 (an adult T cell leukemia cell line, 38%) and low or absent in other cell lines. In fresh samples from AML, ALL, CLL, NHL, myeloma and MDS, no betagal positive cells were seen 48h and 72h after infection, except in one case of myeloma and one case of CLL (where 10% and 2% of betagal positive cells were seen after infection, respectively). Exposure of fresh malignant cells to GM-CSF before and during adenoviral infection, in three cases, did not increase the number of transfected cells. This suggests that adenoviral vectors, at least in their present form, cannot efficiently be used for direct gene transfer in hematological malignant cells.
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PMID:Differential efficacy of adenoviral mediated gene transfer into cells from hematological cell lines and fresh hematological malignancies. 855 24

The proliferative activity of the haematopoietic and plasma cells in bone marrow was evaluated under normal and neoplastic conditions, by means of a sequential double immunostaining technique, using monoclonal antibody MIB-1 recognizing the cell proliferation-associated nuclear antigen Ki-67, and antibodies against glycophorin-C, myeloperoxidase, factor VIII-related antigen, and immunoglobulin light chains. Fifty-eight B5 fixed, paraffin-embedded bone marrow biopsies were analysed, including 11 normal controls. 10 cases of myelodysplasia, 14 cases of chronic myeloproliferative disorder, eight cases of acute non-lymphoid leukaemia, and 15 cases of myeloma. In normal marrows, the highest proliferative activity was noticed in the erythroid cells (75% to 95%; mean 90%), in comparison with myeloid precursors (15% to 80%; mean 38%), and megakaryocytes (10% to 20%; mean 14%): no Ki-67 positive plasma cells were found. In all investigated haematological disorders, the expression of MIB-1 by erythroid cells was similar to that observed in controls. Similarly, the percentage of MIB-1 + myeloid precursors in chronic myeloproliferative disorders and myelodysplasia largely overlapped the values observed in normals, and comparable values were also found in the blast cells from acute non-lymphoid leukaemia type M1 and M2. These findings suggest that the evaluation of either erythroid or myeloid proliferative activity is of little value in the differential diagnosis between these myeloproliferative disorders. By contrast, the obvious increase of Ki-67 expression of megakaryocytes in chronic myeloproliferative disorders, with labelling also of micro-megakaryocytes, might sustain the diagnosis in controversial cases. Since cases of mature myeloma showed less than 2% of Ki-67 positive cells, evaluation of proliferative activity is of no value in the differential diagnosis with reactive plasmacytosis. The sequential double immunophenotyping for Ki-67 antigen and for haematopoietic cell lineage-associated markers can be applied in a consistent manner to routine bone marrow biopsies to evaluate proliferating cells in normal and neoplastic conditions.
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PMID:Assessment of cell proliferation in normal and pathological bone marrow biopsies: a study using double sequential immunophenotyping on paraffin sections. 857 29

A case of acute nonlymphocytic leukemia (ANLL) occurring 2 years after the diagnosis of multiple myeloma (MM) that had been treated by only one course of melphalan/prednisone chemotherapy is reported. Cytogenetic and fluorescence in situ hybridization analysis of peripheral blood cells revealed trisomy 8 as the sole cytogenetic defect at the time of diagnosis of ANLL. Two years earlier, when MM was diagnosed without any cytological evidence of co-existent myelodysplasia, chromosomal analysis of bone marrow cells showed the same pathological karyotype 47, XY, +8 in 14 of 20 mitoses studied. Our interpretation of this unusual cytogenetic finding is that at the time of diagnosis of MM, in spite of lacking cytological signs of myelodysplasia, an unrecognizable myelodysplastic syndrome must have been present which then evolved to ANLL.
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PMID:Trisomy 8 preceding diagnosis of acute nonlymphocytic leukemia by 2 years in a patient with multiple myeloma without cytological evidence of myelodysplasia. 859 11

Transplantation of hematopoietic precursor cells is an established therapy today in the treatment of hematological malignancies. Cells from different sources [bone marrow, peripheral blood, cord blood] and from different donor types [autologous, syngeneic or allogeneic] are used for transplantation. The aim of autologous transplantation is to apply intensive high-dose chemo-radiotherapy and to shorten the duration of aplasia. Allogeneic cells, in addition, are free of potentially contaminating precursor cells and provide a graft-versus-leukemia effect. For all patients, transplantation should be considered at diagnosis as an integral part of treatment strategy and, depending on risk factors, be performed early in the course of disease. Preferred time for patients with high-risk acute leukemias is first complete remission, second complete remission for standard or low-risk acute leukemias. For chronic myeloid leukemia, allogeneic transplantation should be performed within one year of diagnosis, preferably still in first chronic phase. Autologous transplantation can be considered in a protocol setting. For patients with myelodysplastic syndromes of the FAB subtype refractory anemia or refractory anemia with sideroblasts, allogeneic transplantation is the treatment of choice as initial therapy. For patients with refractory anemia and excess of blasts with or without transformation, remission induction should be attempted before transplantation. Autologous transplantation is the preferred treatment strategy for patients with Hodgkin's and non-Hodgkin's lymphoma, for high-risk patients in first complete remission, for other patients in chemotherapy-sensitive first relapse. For patients with myeloma, transplantation should be considered after first line therapy. Age is the main individual patient's risk factor, transplant-related mortality immediately increases in parallel to increasing age. Autologous transplants are limited to patients below 60 to 65 years, allogeneic HLA-identical sibling transplants to patients below 50 to 55 years, and unrelated transplants to patients below 40 to 45 years. Prerequisites for transplant are availability of a donor, access to a transplant bed, informed consent of patient and donor, as well as financial guarantee. Indications for the different hematological malignancies and the major risk factors are discussed.
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PMID:[Indications for bone marrow and peripheral stem cell transplantation in malignant hematological diseases]. 862 66

The clinical course of a 66-year-old man diagnosed with multiple myeloma is described. Chemotherapy including alkylating agents had no effect, and so he was treated with vincristine, doxorubicin, and dexamethasone. His bone tumor was treated with localized radiation after two courses of chemotherapy. After these treatments, monocytosis was found and dysplastic changes were noted in the bone marrow. A cytogenetic study revealed t(9;11)(p22;q23), an abnormality which had previously been absent. A diagnosis of myelodysplastic syndrome (MDS) was newly established, and transformation to acute non-lymphocytic leukaemia (ANLL) was observed 6 months later. The cumulative doses of melphalan, cyclophosphamide, doxorubicin, and radiation therapy were 432 mg, 4,200 mg, 120 mg, and 4,000 cGy, respectively. The cytogenetic abnormality suggested that this patient's MDS/ANLL was related to doxorubicin and not talk to alkylating agents, although the dose of doxorubicin administered was quite low.
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PMID:Acute myelomonocytic leukaemia with 11q23 abnormality during multiple myeloma: is this related to anthracycline? 863 45

The Norwegian Society of Haematology has worked out guidelines for the use of granulocyte-colony stimulating factor and granulocyte-monocyte colony stimulating factor and interferon alpha in clinical haematological practice. We recommend not using growth factors as a routine to prevent or to treat fever in patients with granulocytopenia induced by cytostatics, or patients with myelodysplastic syndromes. At present such treatment should be restricted to clinical trials. The same conclusion was reached in regard to use of erythropoietin in the case of myelodysplastic syndromes. Harvesting of stem cells from peripheral blood is a well documented indication for administration of growth factors. Interferon alpha as maintenance treatment for cases of multiple myeloma and low grade malignant lymphoma delays progression of the disease but does not improve chance of survival. There is no documentation of improved quality of life. Use of interferon alpha is not justified as a routine treatment for multiple myeloma. In chronic myelogenous leukemia, interferon alpha seems to be equal to or better than hydroxyurea, and may be considered for patients who cannot undergo allogeneic bone marrow transplantation.
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PMID:[Treatment with growth factors and cytokines in hematologic diseases]. 880 16


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