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)

Recently, high-dose chemo- and radiotherapy for newly diagnosed young patients with multiple myeloma has been established in member centers of the Nordic Myeloma Study Group (NMSG). The treatment includes supportive use of autologous hematopoietic blood progenitors harvested by leukapheresis. Safe and adequate hematopoietic support with minimal toxicity requires optimization of the number and quality of harvested progenitors. We have therefore established a workshop consisting of the 11 laboratories within the NMSG with the aim of developing recommendations for enumeration of CD34-positive cells. In this first workshop report, we discuss technical variables affecting the enumeration of progenitors harvested by leukapheresis and make specific recommendations. The products are analyzed within 4 h following erythrocyte lysis using the Ortho lysing solution for 8-10 minutes. A sample containing 0.5-1.0 x 10(6) nucleated cells is incubated with the test or control antibody (anti-CD34 = HPCA-2PE and Ms IgG1PE from Becton Dickinson) at dilutions of 1:10 to 1:40 in a final volume of 1 ml. The samples are incubated 15 minutes at ambient temperature, washed two to three times, and fixed with 1% paraformaldehyde (150 microliters/pellet) for a minimum of 10 minutes. Flow cytometric analysis is performed on 50,000 cellular events with debris eliminated. The estimation of CD34-positive cells can be performed on an FL2-side-scatter plot after marking of a positive population containing > 50 events. Using quadrant statistics, this population can be identified in the upper left quadrant, among cells with the side-scatter profile of small lymphocytic cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Report from a Nordic workshop on CD34+ cell analysis: technical recommendations for progenitor cell enumeration in leukapheresis from multiple myeloma patients. Nordic Myeloma Study Group Laboratories. 753 62

The immunoreactivity of paraffin embedded bone marrow biopsies (BMB) was studied following a one step 20-hour-fixation-decalcification in Lowy formalin mercuric chlorid acid solution which permits excellent histological stainings. Antibodies reactive with myeloid, megakaryocytic, erythroid cells, T and B lymphocytes, mastocytes and metastatic cells were compared. Nearly all antibodies working on paraffin sections were demonstrated on Lowy FMA fixed BMB. Special care was taken to define an optimal working dilution. Trypsinization was not necessary. A slide microwave pre-treatment appeared essential before testing CD20 L26, CD8, CD3, CD34, MB1 Kappa and Lambda antibodies. It was suitable for UCHL1, LN2, CD30 antibodies. The same fixative allowed an m RNA Kappa or Lambda in myeloma and EBER 1 EBV RNAs in HIV lymphoma visualization by in situ hybridization. The safety handling of the toxic mercuric chloride component is discussed.
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PMID:Bone marrow one step fixation-decalcification in Lowy FMA solution: an immunohistological and in situ hybridization study. 754 Jul 53

Patients suffering from high-risk multiple myeloma (MM) were randomized to receive single high-dose cyclophosphamide followed by either rhGM-CSF or rhG-CSF in order to harvest circulating peripheral blood progenitor cells. The safety of the procedure, the mobilization kinetics, the relative efficacy of rhGM-CSF and rhG-CSF to mobilize progenitor cells and their relative toxicity were studied. Special attention was paid to the antigenic profile of CD34+ progenitor cells. Group I patients (n = 11) were treated with cyclophosphamide 4 g/m2 i.v. followed by rhGM-CSF at 10 micrograms/kg/d by subcutaneous administration. Group II (n = 11) patients received rhG-CSF s.c. at 10 micrograms/kg/d after the same dose cyclophosphamide. Both mobilization regimens appeared to be equally effective. No significant differences in absolute numbers of circulating progenitors, determined by CD34 expression or in yields of MNC, CFU-GM, BFU-E and CD34 subsets were observed. rhGM-CSF administration resulted however in delayed haemopoietic recovery and an increased complication rate. We conclude that rhG-CSF may be preferred because of its markedly lower toxicity and lower in-hospital costs.
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PMID:Comparative study of peripheral blood progenitor cell collection in patients with multiple myeloma after single-dose cyclophosphamide combined with rhGM-CSF or rhG-CSF. 860 28

A major potential problem of autologous transplantation in the treatment of advanced malignancy is the infusion of tumor cells. A multi-institutional study of purified CD34-selected peripheral blood progenitor cell (PBPC) transplantation was conducted in 37 patients with advanced multiple myeloma receiving myeloablative chemotherapy. Fourteen days after intermediate-dose cyclophosphamide, prednisone, and granulocyte colony-stimulating factor (G-CSF), a median of 3 (range, 2 to 5) 10-L leukaphereses yielded 9.8 x 10(8)/kg (range, 3.7 to 28.3) mononuclear cells. The adsorbed (column-bound) fraction contained 5.9 x 10(6) cells/kg (range, 1.6 to 25.5) with 4.65 x 10(6) CD34 cells/kg (range, 1.2 to 23.3). Using Poisson distribution analysis of positive polymerase chain reactions with patient-specific complementarity-determining region 1 (CDR1) and CDR3 Ig-gene primers, tumor was detected in leukapheresis products from 8 to 14 unselected patients and ranged from 1.13 x 10(4) to 2.14 x 10(6) malignant cells/kg. After CD34 selection, residual tumor was detected in only three patients' products. Overall, a greater than 2.7- to 4.5-log reduction in contaminating multiple myeloma cells was achieved. CD34 PBPCs were infused 1 day after busulfan (14 mg/kg) and cyclophosphamide (120 mg/kg), and granulocyte-macrophage colony-stimulating factor was used until hematologic recovery. The median time to both neutrophil and platelet recovery was 12 days (range, 11 to 16 days and 9 to 52 days, respectively). The median number of erythrocyte and platelet transfusions was 7 (range, 2 to 37) and 3 (range, 0 to 85), respectively. Patients receiving fewer than 2 x 10(6) CD34 cells/kg had significantly prolonged neutropenia, thrombocytopenia, and an increased red blood cell and platelet transfusion requirement. Thus, CD34 selection of PBPCs markedly reduces tumor contamination in multiple myeloma and provides effective hematopoietic support for patients receiving myeloablative therapy.
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PMID:Transplantation of CD34+ peripheral blood progenitor cells after high-dose chemotherapy for patients with advanced multiple myeloma. 754 Aug 88

A case of 77-year-old female with multiple myeloma (IgG-k) developed acute myelomonocytic leukemia (AMMoL) following a myelodysplastic stage after chemotherapy with melphalancyclophosphamide combinations for 6 years. The leukemic blast cells expressed both myeloid antigens (CD11b, CD13, CD14, CD15, CD33 and CD34) and T/B lymphoid antigens (CD2, CD4, CD22 and PCA1). Cytogenetic analysis revealed a chromosome deletion -7. Analysis of immunoglobulin genes showed the heavy chain genes in germ line configuration. These findings indicate that the AMMoL was a therapy-related stem cell leukemia and was a clonal origin genetically different from multiple myeloma irrespective of plasma cell phenotype.
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PMID:Acute myelomonocytic leukemia in a patient with multiple myeloma: evidence for different clonal origin. 754 40

The huge discrepancies in the proportion of tumors positive for P-gp observed in the literature limit any definite conclusions, except for the urgent need for standardized methods to compare results. It is well known by scientists that only positive results are published. For this reason, the frequency of P-gp expression in leukemia and lymphoma may be overestimated. The role of the MDR phenotype in clinical resistance is also not clearly demonstrated, because of the frequent association of other markers of bad prognosis on the same subset of cells (CD34, CD7 in leukemia). Hematologic malignancies are the most extensively studied tumors for drug resistance, and they could be a model for the therapeutic use of modifier agents. Many clinical trials are now ongoing in myeloma, acute leukemia, and lymphoma, with new modifier agents. The standardization of methods for P-gp, permitting large multicentric studies, and the results of randomized studies with modifier agents will help us know if mdr1 gene overexpression is of clinical importance in hematologic malignancies.
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PMID:P-glycoprotein in adult hematologic malignancies. 764 63

Retroviral-mediated gene transfer has been shown to be a feasible method for the introduction of new genes into bone marrow hematopoietic stem cells. We have investigated the application of this technology to primitive CD34-enriched human peripheral blood cells as a potential alternative stem cell source. Bone marrow (BM) and peripheral blood (PB) CD34-enriched cells from normal volunteers and patients with multiple myeloma were exposed to retroviral vectors containing the neomycin-resistance gene and gene transfer efficiency into colony-forming unit colonies (CFU-C) and CD34+ cells was assessed by polymerase chain reaction (PCR). Peripheral blood was a target equally efficient to BM, and PB cells mobilized with chemotherapy and growth factors were also shown to take up retroviral vectors readily. Conditions favoring gene transfer were investigated, and exposure of cells to interleukin-3 (IL-3), interleukin-6 (IL-6), and stem cell factor (SCF) during a 72-hour transduction was found to be most effective. The use of PB stem cells as targets for gene transfer could allow repeated collections and transductions, with obvious advantages over a single BM collection.
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PMID:Retroviral-mediated gene transfer into CD34-enriched human peripheral blood stem cells. 768 85

Positive selection of CD34+ cells has applications in diagnostic pathology, in peripheral blood and bone marrow transplantation, and in studies on the function and regulation of primitive haemopoietic stem cells. Antibody-coated magnetic microspheres (dynabeads) can be used to isolate these cells by positive selection procedures. However, the advantages of using dynabeads in some positive selection protocols are compromised by the retention of the beads on the cells. We present a protocol which allows the rapid chemical release of the beads from positively sorted cells. The murine immunoglobulin (Ig) G1 CD34 antibody, QBEND/10, was immobilised onto dynabeads as part of a three-layered immune complex: QBEND/10 was attached to F(ab')2 anti-mouse immunoglobulin antibody fragments, which were immunologically bound to a mouse IgG1 myeloma protein. The myeloma protein covalently bonded the triplex to the beads. Thus, disulphide bonds in the hinge region of the F(ab')2 could be reduced with 10 microM dithiothreitol and CD34+ cells released within 20 min. Purified cells can be re-phenotyped by multiple markers and subsets identified. Purity of 97%, recovery of > 50%, and viability over 90% of the CD34+ cells was readily achieved. Furthermore, granulocyte-macrophage colony-forming cells were retained in the positive fraction. This methodology can be used to purify other cell types, including T and B lymphocytes.
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PMID:Rapid positive selection of CD34+ cells using magnetic microspheres coated with monoclonal antibody QBEND/10 linked via a cleavable disulphide bond. 768

Two new monoclonal antibodies, Immu-133 and Immu-409, were raised against the human acute myelogenous leukemia cell line (KG-1a) and human immature erythroleukemic cells (TF1). These monoclonal antibodies were isolated from two different fusions of mouse myeloma cells with mouse splenic lymphocytes. The immunofluorescence studies performed on various target cells showed that these antibodies recognized a surface antigen expressed selectively on KG-1a, TF1 cells and on human hematopoietic progenitor cells. They also stained endothelial cells used in immunochemistry both in frozen and paraffin embedded tissue sections. Immu-133 and Immu-409 immunoprecipitated a KG-1a cell surface protein with an apparent molecular weight of 110-115 Kd. Competitive binding assays performed with a panel of referenced CD34 monoclonal antibodies revealed that Immu-133 and Immu-409 are monoclonal antibodies restricted to different epitopes of the CD34 molecule.
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PMID:Isolation and characterization of two new monoclonal antibodies against the CD34 molecule. 768 38

Serial blood and marrow specimens from eight adult recipients of sex-mismatched transplants (BMT) for chronic myeloid leukemia (CML, n = 3), Ewing sarcoma (n = 1), acute myeloid leukemia (AML) in second remission (n = 1), acute lymphatic leukemia (ALL, n = 1) and multiple myeloma (n = 2) were analyzed by the simultaneous immunophenotypic CD3, CD4, CD8, CD20, CD34, CD10 and genotypic analysis (for X and Y chromosomes). This combined technique of moAb/APAAP staining for cell surface and cytoplasmic antigens and fluorescence in situ hybridization (FISH) for the detection of sex chromosomes allowed the qualitative and quantitative evaluation of mixed chimerism and/or relapse. Using the same slides for moAb/APAAP and FISH allowed the simultaneous identification of the cell lineage, the lymphocyte subpopulation and the genotype (XX or YX) in every blood or BM specimen analyzed. A mixed chimerism in the T cell (CD4, CD8+: median 26% host cells, range 5-44%) and in the myelomonocytic cell population (CD14+ median 16% host cells, range 5-50%) was observed at day +7 after BMT. By days +14 to +18 this mixed chimerism was reduced to 18% host T cells (range 5-50%) and 7% host myelomonocytic cells (range 0-20%). Beyond days +21 to +28 a stable donor chimerism for T cells, myelomonocytic cells and granulocytes was observed in seven of eight patients. Still 0.5-1% host cells of different lineages were detectable in five from the eight patients at later time points (> day + 100). In three patients with CML these cells were CD13 or CD13, CD34 positive and in one was CD4, CD8 positive.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detection of mixed chimerism and leukemic relapse after allogeneic bone marrow transplantation in subpopulations of leucocytes by fluorescent in situ hybridization in combination with the simultaneous immunophenotypic analysis of interphase cells. 774 54


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