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

We have investigated the properties of mobilized, cryopreserved, peripheral blood stem cells (PBSC), collected by leukapheresis over a period of 5 days, from eight myeloma patients in clinical remission. Cells were mobilized by treatment with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), and each day's collection was evaluated for its content of CD34+ cells, colony-forming units granulocyte/macrophage (CFU-GM), and plastic-adherent pre-CFU-GM. Peak values for these three parameters were observed at different times in different patients. There was no correlation between CD34+ content and CFU-GM, but there was some (r = 0.65) between CD34 numbers and colonies generated from a delta assay initiated using plastic-adherent pre-CFU-GM. In suspension cultures, the cells grew exponentially for 50 days. Thereafter, they did not divide, although they remained viable in culture for up to 1 month longer. Suspension cultures of PBSC grown with interleukin-3 (IL-3) displayed a predominantly myelomonocytic phenotype, but some megakaryocytes and erythroid cells were observed consistently. These results indicate that pre-CFU-GM in PBSC collections are capable of generating large numbers of clonogenic progeny in liquid culture and are capable of producing multiple lineages of differentiation.
 ...
PMID:In vitro proliferation by cells mobilized into the peripheral blood for collection and autologous transplantation. 752 29

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.
 ...
PMID:Bone marrow one step fixation-decalcification in Lowy FMA solution: an immunohistological and in situ hybridization study. 754 Jul 53

Recombinant human erythropoietin (rHu-EPO) is an effective growth factor for erythroid progenitor cells in anemia provoked by several conditions, including bone marrow tumors such as multiple myeloma (MM). We studied a group of 54 patients with MM undergoing second-induction chemotherapy. Thirty of them were randomly assigned to receive rHu-EPO at an initial dosage of 150 units/kg body weight three times a week, increased to 300 units/kg from the sixth week to the end of the 24-week study. Hemoglobin (Hb) levels increased in 77.7% of these patients by the eighth week. In addition, five transfusion-dependent patients in treatment with the VMCP protocol completed the trial without requiring blood supplement after the third month, whereas seven control patients required frequent supplements. Monthly assessment of hematologic parameters demonstrated the ability of rHu-EPO to increase reticulocyte counts, whereas five patients became resistant to the second-induction chemotherapy in apparent concurrence with their rHu-EPO therapy. The response to rHu-EPO in four of the five MM patients receiving cytotoxic protocols combined with alpha-interferon (alpha-IFN) included an increase of serum IgM after the third month. This effect was not demonstrable in any other group, including three rHu-EPO-untreated patients undergoing alpha-IFN + VMCP combined therapy, as well as rHu-EPO-treated patients not receiving alpha-IFN. Our data suggest that alpha-IFN plus rHu-EPO treatment in MM patients is effective in restoring normal B cell function. These results may reflect in vivo the modulation of normal human B cells and lymphoblasts by rHu-EPO observed in vitro.
 ...
PMID:Long-term therapy with recombinant human erythropoietin (rHu-EPO) in progressing multiple myeloma. 763 11

The Danish Thorotrast Study was recently reestablished and improved. The cohort has been reidentified and followed up, and now comprises 1003 Thorotrast-exposed patients. For all suspected haematological cases, cytological and histological material has been revised and malignant diseases have been reclassified. The numbers of cases of leukemia and other related haematological disorders were as follows: 16 acute myeloid leukemia (AML); 8 myelodysplastic syndrome (MDS); 1 acute lymphatic leukemia (ALL); 3 chronic myeloid leukemia (CML); 4 non-Hodgkin's lymphoma (NHL); 2 multiple myeloma (MM); 2 myelofibrosis (MF); 2 chronic lymphatic leukemia (CLL). Except for CLL, all cases might be Thorotrast-induced. (Expected number of leukemias: < 2.5.) The findings in the German, Japanese, Portuguese and Danish studies are very similar. Some of the characteristic features include a high incidence of AML with several erythroleukemias, many cases of MDS, and a relatively low incidence of CML. In several studies of leukemia induced by alkylating agents, erythroleukemia is also described as a prominent feature. The possibility exists that a phase of relative predominance of erythroid elements in the bone marrow may be a common and not an unusual feature in the pathogenesis of these secondary leukemias. The findings are also compared with histopathological data from a Danish control group of de novo leukemia patients and from atomic bomb survivors with radiation-induced leukemia. The relative frequency of AML is higher among the Thorotrast-exposed patients than among the Danish control group and the A-bomb survivors. In contrast, low relative frequencies are seen for ALL and CML in Thorotrast cases in comparison with de novo leukemia cases and A-bomb survivors. It can be concluded that differences in relative and absolute frequency of leukemias and myelodysplastic syndrome exist not only between the irradiated populations and the unexposed control group, but even between groups exposed to low-LET (linear energy transfer) and high-LET radiation.
 ...
PMID:Pathoanatomical aspects of malignant haematological disorders among Danish patients exposed to thorium dioxide. 769 89

Congenital dyserythropoietic anemia, type III (CDA III) is a rare autosomal dominant disorder characterized by macrocytic anemia, bone marrow erythroid hyperplasia and giant multinucleate erythroblasts. We have genetically characterized a large Swedish family in which the concurrence of CDA III and myeloma or benign monoclonal gammopathy is significantly higher than expected and have found that the causative genetic defect for CDA III maps to an 11 cM interval within 15q21-q25.
 ...
PMID:Localization of the gene for congenital dyserythropoietic anemia type III, CDAN3, to chromosome 15q21-q25. 771 21

A retrospective analysis of long-term hematopoiesis was performed in a group of 145 consecutive patients who had received high-dose therapy with peripheral blood progenitor cell (PBPC) support between May 1985 and December 1993. Twenty-two patients had acute myelogenous leukemia, nine had acute lymphoblastic leukemia, 43 had Hodgkin's disease, 57 had non-Hodgkin's lymphoma, and 14 patients had multiple myeloma. Eighty-four patients were male and 61 female, with a median age of 37 years (range, 16 to 58 years). In 46 patients, PBPC were collected after cytotoxic chemotherapy alone, while 99 patients received cytokines either during steady-state hematopoiesis or post-chemotherapy. Sixty patients were treated with dose-escalated polychemotherapy, and 85 patients had a conditioning therapy including hyperfractionated total body irradiation at a total dose of 14.4 Gy. The duration of severe pancytopenia posttransplantation was inversely related to the number of reinfused granulocyte-macrophage colony-forming units (CFU-GM) and CD34+ cells. Threshold quantities of 2.5 x 10(6) CD34+ cells per kilogram or 12.0 x 10(4) CFU-GM per kilogram became evident and were associated with rapid neutrophil and platelet recovery within less than 18 and 14 days, respectively. These numbers were also predictive for long-term reconstitution, indicating that normal blood counts are likely to be achieved within less than 10 months after transplantation. Conversely, 12 patients were autografted with a median of 1.75 x 10(4) CFU-GM per kilogram resulting in delayed recovery to platelet counts of greater than 150 x 10(9)/L between 1 and 6 years. Our study includes bone marrow examinations in 50 patients performed at a median follow-up time of 10 months (range, 1 to 85 months) posttransplantation. A comparison with normal volunteers showed a 3.2-fold smaller proportion of bone marrow CD34+ cells, which was paralleled by an even more pronounced reduction in the plating efficiency of CFU-GM and burst-forming unit-erythroid. No secondary graft failure was observed, even in patients autografted with relatively low numbers of progenitor cells. This suggests that either the pretransplant regimens were not myeloablative, allowing autochthonous recovery, or that a small number of cells capable of perpetual self-renewal were included in the autograft products.
 ...
PMID:Sustained long-term hematopoiesis after myeloablative therapy with peripheral blood progenitor cell support. 778 Jan 58

T cells in multiple myeloma (MM) patients are highly susceptible to activation with the anti-CD3 monoclonal antibody (mAb) OKT3. When short-term OKT3 stimulation is carried out on bone marrow mononuclear cells (BMMC), large numbers of CD3+ CD25+ HLA-DR+ cells are rapidly generated and autologous malignant plasma cells are killed. OKT3 may thus be exploited in autologous bone marrow transplantation (ABMT) to purge residual plasma cells and simultaneously activate T cells to induce graft-versus-leukemia-like (GVL-like) activity upon reinfusion. However, the possible impact of ex-vivo short-term OKT3 stimulation on haematological recovery is unknown. The aim of this work was to investigate the effect of OKT3 stimulation in vitro on autologous haemopoietic progenitor cells (HPC) of MM patients. Colony formation by granulocyte-macrophage progenitor cells (granulocyte-macrophage colony-forming units, CFU-GM) was highly suppressed, although supernatants of OKT3-activated T cells contained up to 2,500 pg/ml of granulocyte-macrophage colony-stimulating factor (GM-CSF). T cell depletion completely prevented this suppression. Neutralizing antibodies against TNF-alpha, TNF-beta and IFN-gamma (which are also produced by OKT3-activated MM T cells) did not prevent it, and Transwell cultures showed that cell-to-cell contact was the main mechanism involved. OKT3-activated T cells also suppressed erythroid burst-forming units (BFU-E) and CFU-GM generation from HPC responsible for long-term maintenance of in vitro myelopoiesis. When tested on normal allogeneic BM, MM supernatants of OKT3-stimulated BMMC partially suppressed the generation of day 7 CFU-GM, but had no effect on day 14 CFU-GM. These data indicate that short-term stimulation of BMMC with OKT3 can be used to generate anti-tumour effector T cells for autologous adoptive immunotherapy. It is not a feasable approach for ex-vivo purging and activation procedures in ABMT because of its potent inhibition of autologous haemopoiesis.
 ...
PMID:Generation of anti-tumour activity by OKT3-stimulation in multiple myeloma: in vitro inhibition of autologous haemopoiesis. 799 89

Peripheral blood stem cells (PBSC) from 15 patients with advanced non-Hodgkin's lymphoma (NHL), two patients with chronic lymphocytic leukemia, and two patients with myeloma were collected by continuous-flow leukapheresis after chemotherapy with MIV (mitoxantrone, ifosfamide, and etoposide, five patients) or high-dose cyclophosphamide (14 patients), followed by administration of GM-CSF. Sixteen patients (84%) had persistent marrow involvement at time of inclusion. Results were compared to those obtained in a control group of similar age and disease status in whom collection had been performed after MIV chemotherapy alone. The number of mononuclear cells, granulocyte-macrophage colony-forming units (CFU-GM), CD34+ cells were higher in GM-CSF treated patients with a lower mean number of leukapheresis (3.5 versus 6.4). Among the 19 patients harvested after chemotherapy plus GM-CSF, more progenitor cells were obtained in the cyclophosphamide group than in the MIV group. In all these patients except one, the number of mononuclear cells was sufficient to realize a transplantation. Seventeen patients received intensification with BEAM regimen (8 patients) or cyclophosphamide plus etoposide and total body irradiation (9 patients). Two patients failed to reconstitute correct hematopoiesis and three early toxic deaths occurred for a total of five procedure-related deaths. Nine of these 17 patients are in persistent complete remission with a median post-transplant follow-up of 18 months. Time to reach granulocyte and platelet recovery was not correlated with the number of mononuclear cells, CFU-GM, granulocyte-erythroid-macrophage-megakaryocyte colony-forming units (CFU-GEMM), CD34+ cells, and CD34+ CD33- cells but with the number of previous chemotherapy regimens. PBSC harvesting is achievable after chemotherapy plus GM-CSF in heavily pretreated patients with persistent marrow involvement. Moreover, these cells are able to reconstitute correct hematopoiesis after intensive treatment in these patients.
 ...
PMID:Peripheral blood stem cells harvested after chemotherapy and GM-CSF for treatment intensification in patients with advanced lymphoproliferative diseases. 810 11

Anemia is a common complication of patients with multiple myeloma (MM) and myelodysplastic syndrome (MDS). Most of these patients often require blood transfusion. 12 patients, including 7 cases of MM and 5 cases of MDS, were treated with rhEPO 10,000 micrograms three times a week for 15 weeks. The hemoglobin in 6 of 7 cases of MM steadily increased and eventually reached normal level without blood transfusion. The number of erythroid precursors in bone marrow was increased significantly and serum ferritin concentration was decreased gradually during EPO administration. However 5 patients with MDS did not show any response to EPO. The adverse side effects were hardly observed in any patients received EPO treatment. It is suggested that rhEPO is a promising preparation for treating MM-associated anemia rather than MDS-associated anemia.
 ...
PMID:[Erythropoietin treatment of anemia associated with multiple myeloma (MM) and myelodysplastic syndrome (MDS)]. 822 21

The cytotoxicity of a recombinant interleukin 6 (IL-6)-diphtheria toxin (DT) fusion protein towards human myeloma cell lines was investigated. DAB389-IL-6 inhibited protein synthesis and methylcellulose colony formation by U266 myeloma cells. In the clonogenic assay, the fusion protein approached the level of cytotoxicity achieved by native DT. The specificity of killing by DAB389-IL-6 was demonstrated by inhibition of cytotoxicity by a molar excess of free rhIL-6. The effect of DAB389-IL-6 on colony formation by six OCI-My cell lines was assessed. Similar to U266 cells, colony growth by the OCI-My 5 and -My 2 cell lines was inhibited in a simple dose dependent manner. However, a biphasic effect was observed for the IL-6 dependent OCI-My 4 cells; DAB389-IL-6 stimulated colony formation at low (< or = 10(-11) M) concentrations, yet was inhibitory at higher doses. Three other cell lines whose growth was not altered by IL-6 were relatively unaffected by DAB389-IL-6, despite their sensitivity to native DT. Flow cytometric analysis for IL-6 receptor expression using phycoerythrin-conjugated IL-6 demonstrated specific binding sites on both DAB389-IL-6 sensitive and certain insensitive cell lines, suggesting that other factors in addition to the expression of IL-6 receptors are involved in killing by the fusion toxin. Despite evidence for a role of IL-6 in myeloid cell development, normal bone marrow was insensitive to the IL-6 fusion toxin. In cultures containing both normal bone marrow and U266 cells DAB389-IL-6 effectively inhibited the growth of U266 myeloma colonies but had little effect on normal bone marrow erythroid, granulocyte and mixed erythroid/granulocyte colony growth. From these experiments we conclude that DAB389-IL-6 is specifically cytotoxic towards a subset of IL-6-responsive human myeloma cell lines and may be useful, in some cases, in the selective elimination of tumour cells from mixed populations of normal and malignant cells.
 ...
PMID:Differential sensitivity of human myeloma cell lines and normal bone marrow colony forming cells to a recombinant diphtheria toxin-interleukin 6 fusion protein. 825 7


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>