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)

Twenty-eight patients with different hematological diseases (17 non-Hodgkin's lymphoma, one Hodgkin's disease and 10 multiple myeloma) underwent peripheral blood progenitor cell (PBPC) collection after cyclophosphamide 7 g/m2 and rh-G-CSF. Fifty-eight leukaphereses were carried out with a fully automated PBPC collection procedure. Progenitor cell release was monitored by standardized determination of CD34+ cells in the peripheral blood. After a profound aplasia, a continuous increase in CD34+ cells in the peripheral blood was seen for at least 3-4 days. In 82% of our patients more than 2.5 x 10(6) CD34/kg could be collected using a standard apheresis of 10 l. There was a high correlation between the CD34+ cells in the peripheral blood and CD34+ cells/kg harvested. (r2 = 0.91). A relatively constant ratio (median 14.3, range 3.2-22.6) was found between CD34+ cells/kg and CFU-GM/kg. Based on the CD34 values of the pre-apheresis blood and the body weight of an individual patient and using the mathematical model of regression analysis (y = mx + b) for the correlation between the CD34+ cells/microliter in the pre-apheresis blood and the CD34+ cells/kg, it was possible to create a formula allowing for target value tailored apheresis. Using this formula, the blood volume which needs to be processed in order to harvest a desired number of CD34+ cells/kg can be calculated. This strategy can be applied to reduce the time for and the number of aphereses. Nineteen leukaphereses were carried out applying the formula. In 18 of 19 leukaphereses the expected CD34+/kg values were correctly achieved or exceeded. The formula was most reliable when the CD34 value was higher than 15/microliter and when the WBC count was below 20 x 10(9)/l in the pre-apheresis blood. For mobilizations using hematopoietic growth factors alone our formula is not applicable, because in most cases the pre-apheresis white blood cell count is higher than 20 x 10(9)/l and the collection efficacy of lymphomonocytoid cells decreases with a high pre-apheresis white blood cell count. The formula also works with other mobilization regimens that induce a pronounced aplasia.
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PMID:Target value tailored (TVT) apheresis approach for blood progenitor cell collection after high-dose chemotherapy and rh-G-CSF. 887 26

We studied the feasibility of in vitro expansion of CD34+ cells from patients with multiple myeloma (MM) or follicular non Hodgkin lymphoma (NHL). CD34+ cells were selected from peripheral blood (PB) using avidinbiotin immunoadsorption columns: purified CD34+ cells from three MM and five NHL patients were expanded. First, CD34+ cells (2 MM, 4 NHL) were grown for 14 days in 5 ml of IMDM plus 12.5% horse serum (HS), 12.5% fetal calf serum (FCS) and a commonly used combination of cytokines: IL1alpha, IL3, IL6, SCF, GM-CSF, G-CSF (10 ng/ml each) and EP (4 UI/ml). In these conditions, at day 14, average increase in CD34+, CFU-GM and total cell numbers were, respectively: x 6.0 x 23 and x 2,113 fold with 20 to 35% of granulocytic cells. In terms of CD34+ cell, CFU-GM and total cell outputs, MM cultures were comparable to NHL cultures, but MM cultures seemed to produce less granulocytic cells than NHL cultures. Next, in vitro expansion of PB CD34+ cells was tested in culture media suitable for clinical use. Two cultures (1 MM, 1 NHL) were carried out for 14 days in 20 ml of X-Vivo 10 medium, 2% human serum, IL1alpha, IL3, IL6, SCF, GM-CSF, G-CSF (6 ng/ml each) and EP (2 UI/ml). Increase in CD34+, CFU-GM and total cell numbers in these conditions were, respectively: x 5.7 and x 19.7, x 11.9 and x 40.9, x 424 and x 408 fold, with at least 75% of granulocytic cells in both cultures. We conclude that, although further improvements are necessary, in vitro expansion of PB CD34+ cells can presumably be carried out successfully for MM patients as well as for NHL patients, including in conditions suitable for clinical use.
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PMID:In vitro expansion of CD34+ cells from peripheral blood of myeloma and lymphoma patients. 890 29

Peripheral blood stem cells (PBSC) are used increasingly for autotransplantation in the treatment of acute leukemia, lymphoma, multiple myeloma, solid tumors such as ovarian and breast carcinoma. They are collected by leukaphereses during rapid hematopoietic recovery, following cytotoxic chemotherapy with or without administration of hematopoietic growth factors. We studied the clonogenic and cytokine-mediated expansion potential of CD34+ cells from mobilized PBSC. Low density mononuclear cells were processed using the CEPRATE LC CD34 KIT (CellPro). CD34+ purified cells, were cultured in suspension with 6 combined hematopoietic growth factors (IL1beta, IL3, IL6 at 100 U/ml and G-CSF, GM-CSF and stem cell factor at 10 ng/ml of each) for up to four weeks. Every week, cells were counted and CFU-GM assay was performed in a methylcellulose based medium. We have analysed the percentage of cells bearing CD34, CD33, CD38, HLA-DR, CD45RA, CD45RO antigens. Our results showed, that CD34+ cells were obtained with a purity of 92 +/- 2.3% and a yield of 71 +/- 10.7%. The majority co-expressed CD33 (57.76 +/- 34.16%) and CD38 (62.2 +/- 34%) antigens. These culture conditions, are necessary to obtain a fold increase of nucleated cells (377 fold at week 4), of CFU-GM progenitors (41.2 fold at week 3) and of CD34+ cell absolute number (10 fold at week 1) with an important differentiation of progenitors in particular myeloid progenitors.
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PMID:Peripheral blood CD34+ cells: method of purification and ex vivo expansion. 890 32

Between October 1991 and May 1994, 42 patients were treated with cyclophosphamide, thiotepa, and total body irradiation followed by an allogeneic transplantation of marrow depleted of T cells with soybean agglutinin and E-rosetting. Patients included in this study had acute myelogenous leukemia (13), chronic myelogenous leukemia (12), acute lymphocytic leukemia (nine), Hodgkin's disease or non-Hodgkin's lymphoma (four), multiple myeloma (three), or myelodysplastic syndrome (one). The mean age was 34 (range 8 to 51 years). Nineteen patients had a matched sibling donor and 18 received marrow from 6/6 matched unrelated donors while five received transplants from unrelated donors disparate at one DR locus (5/6 match). Time to granulocyte engraftment (AGC > or = 500/mm3) occurred at a mean of 16.5 days for related and 11.4 days for unrelated transplant recipients, and was related to the increased use of G-CSF in the unrelated population. There was no correlation with number of mononuclear cells, T cells, or CD34-positive cells infused, the rate of engraftment or the incidence of transplant complications. Multivariate analysis determined that G-CSF administration and a diagnosis other than ALL were the only factors associated with a faster rate of engraftment. Patients receiving unrelated donor transplants, those with ALL, or those who had a low T cell number infused (< or = 8.0 x 10(3) cells/kg) experienced delayed hospital discharge. The regimen resulted in excellent rates of engraftment (95.2%) with only one failure to engraft and one graft rejection. The incidence of grade III-IV acute graft-versus-host disease was 0% with sibling and 26.1% with unrelated donors. There were no cases of veno-occlusive disease. Fifty percent of patients are alive with a mean follow-up of 26.4 months. We conclude that this regimen is well tolerated and results in excellent engraftment with a low incidence of severe graft-versus-host disease and few therapy-related toxicities.
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PMID:Minimizing graft rejection in allogeneic T cell-depleted bone marrow transplantation. 893 45

Necrotizing fasciitis is a rare but often fatal soft-tissue infection primarily involving the superficial fascia and fat tissue resulting in extensive undermining of surrounding tissues. Skin is initially spared, but as necrotizing fasciitis spreads, all the soft-tissue components, including the skin, become involved. The progression of necrotizing fasciitis is often fulminant, and the prognosis depends to a large extent on the rapidity of correct diagnosis and surgical treatment (debridement). Most of the patients affected with necrotizing fasciitis have some risk factors: chronic general or local diseases, leukopenia, immunodeficiency diseases, malignancies, and an age of 50 years or more. The author reported the occurrence of necrotizing fasciitis in a 69-year-old man with multiple myeloma during the granulocytopenic phase after chemotherapy. The successful treatment of necrotizing fasciitis in the present case relied not only on surgical debridement, but also on G-CSF administration.
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PMID:[Multiple myeloma complicated by necrotizing fasciitis]. 896 Jun 67

Although IL-6 has been identified as a major growth factor in multiple myeloma (MM), it is believed that maintenance of tumor growth in vivo depends on one or more additional stroma-derived factors. We describe a new human myeloma cell line (MM5.1) that can be maintained in the presence of bone marrow-derived stromal cell layers, and not only when cultured with exogeneous IL-6. This cell line expresses the same immunoglobulin kappa light chain RNA sequence as the patient's original tumor cells, has a plasma cell morphology and expresses plasma cell antigens (cytoplasmic kappa light chain, CD38, BB4). Without the presence of stromal factors, MM5.1 cells become apoptotic. A low proliferative effect was observed in the presence of oncostatin M (OSM) but other cytokines (IL-10, IL-11, stem cell factor (SCF) and leukemia inhibitory factor (LIF)) had no effect at all. We observed that MM5.1 cells also grow when physically separated from stromal cell layers by a 0.45 microm microporous membrane or when cultured in conditioned medium from stromal marrow cells. Unexpectedly, the growth in stromal supernatants was markedly inhibited by an anti-IL-6 antiserum and an anti-IL-6 receptor transducer chain (gp130) mAb in a dose-dependent manner. This implies that MM5.1 cells are IL-6 responsive only when exposed to one or more additional soluble factor(s) derived from bone marrow stroma. Coculturing MM5.1 cells with IL-6 and cytokines that were described to increase the IL-6 responsiveness of myeloma cells (G-CSF, GM-CSF and IL-3) had no effect on the growth or survival. A strong proliferative effect was observed when MM5.1 cells were cultured with IL-6 and soluble IL-6 receptor (sgp80). However no sgp80 could be detected in stromal supernatants using a sensitive immunoassay. This indicates that sustained proliferation of the MM5.1 cell line depends on a combination of IL6 and at least one, thus far unidentified, stroma-derived factor. After more than 1 year in continuous culture, we could obtain a variant of the line (MM5.2) that shows an improved growth rate and grows stroma independently. Molecular analysis revealed clonal identity with the early passage form and Epstein-Barr virus antigen expression was negative. The two variants of this cell line offer a useful model to identify molecular mechanisms involved in clonal evolution towards stroma-independent growth of myeloma cells.
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PMID:Establishment and characterization of a human stroma-dependent myeloma cell line (MM5.1) and its stroma-independent variant (MM5.2). 900 94

G-CSF is routinely administered after autologous bone marrow or peripheral blood progenitor cell transplantation to enhance neutrophil engraftment. However, many different doses of G-CSF have been described with no clear consensus on the most cost-effective dose. We performed a prospective randomized trial examining the efficacy of three different doses of G-CSF post-autologous transplant (5, 10, or 16 micrograms/kg/day). Fifty-seven consecutive patients with breast cancer (n = 30), non-Hodgkin's lymphoma (n = 16), Hodgkin's disease (n = 6), multiple myeloma (n = 2), acute leukemia (n = 2), and testicular cancer (n = 1) were randomized, with 19 patients enrolled in each of the three treatment groups. All patients underwent a high-dose chemotherapy preparative regimen and received an autologous peripheral blood progenitor cell (PBPC) transplant (without bone marrow), with G-CSF beginning on day 0. There was no difference in time to neutrophil engraftment among the three treatment groups (mean 10.2 to 10.8 days). There is a trend towards earlier platelet engraftment in the patient group receiving 5 microgram/kg/day of G-CSF. The total cost of G-CSF by dose group was $2900, $4400, and $6500 per patient. We conclude that there was no advantage to the use of higher doses of G-CSF after autologous transplantation, and that lower doses are associated with lower costs.
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PMID:G-CSF post-autologous progenitor cell transplantation: a randomized study of 5, 10, and 16 micrograms/kg/day. 902 48

Mobilized CD34+ blood cells were immunomagnetically enriched from leukapheresis products in five multiple myeloma (MM) patients. Thawed samples of selected CD34+ cells were cultured for up to 21 d in a liquid and stroma-free culture system with different combinations of recombinant cytokines. The most successful cell expansion was obtained when a combination of rh-IL-1beta, rh-IL-3, rh-IL-6, rh-SCF, rh-G-CSF and rh-GM-CSF was used. After 14 d this mixture gave a 120-187-fold overall increase of total nuclear cells and a 4-8-fold overall increase of early CFU-GM numbers. In four patients a very sensitive patient-specific PCR analysis showed the presence of monoclonal cells in the initial leukapheresis products. After immunomagnetic separation a tumour cell depletion of 2-4 logs was observed, although all samples still contained malignant cells. Cell suspensions that were cultured with the most potent cytokine combination showed tumour contamination in two-thirds of evaluable cases at the moment of maximal CFU-GM output. Serial cDNA dilution experiments indicated that the positive PCR results at day 14 reflected the persistence of pre-culture tumour cells rather than in vitro expansion of tumour cells in two cases. This study demonstrates that ex vivo expansion of myeloid precursor cells from mobilized CD34+ cells in MM patients does not always result in an effective purging of residual tumour cells. On the other hand, our culture conditions do not seem to favour in vitro expansion of malignant cells, despite the use of a cytokine cocktail that includes potential myeloma growth factors.
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PMID:Persistence of residual tumour cells after cytokine-mediated ex vivo expansion of mobilized CD34+ blood cells in multiple myeloma. 902 33

The feasibility of ex vivo expansion of hematopoietic progenitors selected from leukapheresis products of patients treated for multiple myeloma (MM) was studied and compared with progenitor expansions from patients with nodular non-Hodgkin's lymphoma (NHL) or healthy donors. After positive selection, CD34+ cells from leukapheresis products of 4 MM and 5 NHL patients and CD34+ cells from bone marrow (BM) of 3 healthy donors were grown in IMDM plus 12.5% horse serum, 12.5% fetal calf serum, IL-1alpha, IL-3, IL-6, SCF, GM-CSF, G-CSF (10 ng/ml each), and EP (4 UI/ml). Outputs of CD34+ cell cultures from MM and NHL patients were similar. Day 14 mean increases in CD34+, CFU-GM, and total cell numbers were, respectively, 5.3-fold, 19.8-fold, and 1173-fold for MM patients and 4.3-fold, 15.6-fold, and 1659-fold for NHL patients, with at least 40% of day 14 cells being of granulocytic lineage. Patient CD34+ cell culture output was found to be related to the CFU-GM/CD34+ cell ratio of selected CD34+ cells, not to underlying pathology. When the initial CFU-GM/CD34+ cell ratio was above 0.025, MM and NHL CD34+ cell culture outputs were always above 1000-fold. Moreover, in all but one CD34+ cell culture, the use of fibronectin (FN)-coated dishes improved CFU-GM and total cell expansion. In patient CD34+ cultures carried out in FN-coated dishes, mean day 14 CFU-GM and total cell outputs were increased, respectively, 2.1-fold and 1.9-fold. We conclude that if the CFU-GM/CD34+ cell ratio is sufficient (>0.025), ex vivo expansion of hematopoietic progenitors from CD34+ cells selected from leukapheresis products is possible for both MM and NHL patients and that using FN-coated flasks is a simple and reliable way to improve both CFU-GM and total cell output.
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PMID:Ex vivo expansion of hematopoietic progenitors from CD34+ cells selected from leukapheresis products of lymphoma and myeloma patients: feasibility and enhancement by fibronectin. 911 56

For blood progenitor cell (BPC) mobilization, standard-dose VIP chemotherapy consisting of etoposide, ifosfamide and cisplatin has previously shown effective tumor reduction in solid tumor patients and sufficient progenitor cell mobilization for autologous blood cell transplantation. Mobilization chemotherapy regimens in multiple myeloma (MM) predominantly consist of melphalan or cyclophosphamide that induce marked cytopenia and considerable variability of progenitor cell collection. We studied whether in MM (n = 13), BPCs were efficiently and reproducibly mobilized with etoposide (500 mg/m2) and ifosfamide (1500 mg/m2), followed by daily s.c. G-CSF (5 micrograms/kg). In parallel, patients with solid tumors or non-Hodgkin's lymphomas (n = 28) treated with etoposide (500 mg/m2), ifosfamide (1500 mg/m2) and cisplatin (150 mg/m2) and identical dosing of G-CSF were analyzed. Before chemotherapy (day 0), on day 7 after chemotherapy and on days of leukapheresis (day 9-14), leukocyte numbers, mononuclear cells (MNCs), CD34+ cells and coexpression of lineage markers were analyzed. Median blood leukocyte numbers were 28,100/microliters (range, 19,600-40,400) on day 10 in myeloma patients and progressively declined over the next 4 days. In contrast, in solid tumor and lymphoma patients leukocyte numbers constantly increased from a median of 12,400/microliters (range, 6000-22,000) to 30,000/microliters (range, 16,300-63,300) between day 10 and day 13 after chemotherapy. Similar to leukocyte counts, median MNC numbers decreased in myeloma patients with successive leukaphereses, but steadily increased in solid tumor and lymphoma patients over the same period. CD34+ cell numbers in the blood peaked between day 9 and 11 (median: 40/microliters) in myeloma patients and then declined. In the solid tumor and lymphoma group, median CD34+ counts in the blood peaked on day 12 after mobilization chemotherapy (median: 100/microliters). The median CD34+ yield per leukapheresis in the myeloma group was 2.2 x 10(6)/kg (range, 1.5-4.7) on day 10, and fell steadily to 0.95 x 10(6)/kg on day 12, whereas in solid tumor/NHL patients median CD34+ cell yields remained between 3.5 and 3.7 x 10(6)/kg from day 10 to day 12 after mobilization chemotherapy (P < 0.001). To obtain sufficient cell numbers for engraftment a median of 2 (range, 1-3) mobilization chemotherapy cycles were needed in MM compared to 1 (range, 1-10) in solid tumor or lymphoma patients, with a median of 5 (range, 2-8) leukaphereses in MM compared to 1 (range, 1-10) (P < 0.05). Taken together, we found that for patients with MM, VP16 and ifosfamide efficiently and predictably mobilizes progenitor cells into the PB with > or = 3 x 10(6)/kg CD34+ cells collected after one to two mobilization chemotherapy cycles.
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PMID:Blood progenitor cell (BPC) mobilization studied in multiple myeloma, solid tumor and non-Hodgkin's lymphoma patients after combination chemotherapy and G-CSF. 918 98


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