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)

Factors affecting mobilization and engraftment were analysed in 54 patients undergoing transplant using autologous PBSCs mobilized with high-dose recombinant granulocyte stimulating factor (rhG-CSF). Patients received 5-7 d of rhG-CSF, 16 micrograms/kg/d, administered subcutaneously. PBSCs were harvested by leukapheresis using automated continuous-flow blood cell separators beginning on day 4 of rhG-CSF, processing 10 litres of whole blood, for 2-6 consecutive days. Transplants were performed for the following diseases: breast cancer (n = 22), non-Hodgkin's lymphoma (n = 18), multiple myeloma (n = 7) and other (n = 7). Engraftment was rapid with patients reaching a neutrophil count of 1 x 10(9)/l a median of 12 d (range 9-22) after transplant. Platelets > 20 x 10(9)/l independent of transfusion support were achieved a median of day 10 (range 7-60) after infusion. Multiple factors potentially influencing engraftment were examined using a Cox regression model. The number of CD34+ cells per kg was highly correlated with the time to achievement of granulocyte and platelet recovery (P < 0.012, 0.0001). The use of a post-infusion growth factor and a radiation preparative regimen was important for neutrophil recovery, and a diagnosis of breast cancer was important for platelet recovery. In an analysis by linear regression of the logarithm of CD34+ cells collected, lower age, marrow without disease, no prior radiation, and lower number of prior chemotherapy regimens, were important factors influencing larger numbers of CD34+ cells in collections.
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PMID:Peripheral blood stem cells (PBSCs) collected after recombinant granulocyte colony stimulating factor (rhG-CSF): an analysis of factors correlating with the tempo of engraftment after transplantation. 753 30

To find out which cytokines are involved in the pathogenesis of multiple myeloma, we investigated cytokine receptor expression on myeloma cells using a panel of monoclonal antibodies (MoAbs). Flow cytometric analysis of five myeloma cell lines (RPMI8226, ARH77, KMM-1, U266, and Hs) and myeloma cells freshly isolated from eight patients showed that interleukin-1 receptor (IL-1R) type I and type II, IL-2R alpha and beta chains, IL-4R, IL-6R, IL-7R, IL-8R, granulocyte macrophage colony-stimulating factor receptor (GM-CSFR), c-kit (stem cell factor receptor [SCFR]), membrane bound stem cell factor (MBSCF), and tumor necrosis factor (TNF) receptors type I and type II were not always detected on the myeloma cells. However, interferon-gamma receptor, gp130, and Fas antigen were constitutively expressed, except one sample. To determine the role of Fas antigen on myeloma cells, these cells were cultured with anti-Fas MoAb. Apoptotic changes characterized by loss of cell volume, membrane blebbing, fragmentation of nuclei, and condensed chromatin were observed in three of five myeloma cell lines. When bcl-2 expression was examined, it was seen in all the cell lines regardless of the sensitivity to anti-Fas MoAb. Furthermore, anti-Fas MoAb not only induced apoptosis of freshly isolated myeloma cells but also inhibited the DNA synthesis, although such effects varied from patient to patient. The data indicate that only some myeloma cells undergo apoptosis in response to the signal mediated by the Fas antigen.
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PMID:Myeloma cells express Fas antigen/APO-1 (CD95) but only some are sensitive to anti-Fas antibody resulting in apoptosis. 753 May 6

A combination antibacterial therapy with fosfomycin (FOM) and sulbactam/cefoperazone (SBT/CPZ) was applied to 78 patients with severe infections associated with hematological diseases. In this protocol, FOM was followed by SBT/CPZ and each drug was administered for 1 hour intravenously and consecutively. Among 72 evaluable patients, 43 patients had acute leukemia, myeloblastic or lymphoblastic, 22 had malignant lymphoma, 3 had multiple myeloma, and 4 had other hematological diseases as underlying diseases. Bacterial infections diagnosed were sepsis in 21 patients, suspected sepsis in 47, and other infections in 4. The overall efficacy rate of this treatment was 72.2%, and those for individual infections were 66.7% for sepsis, 74.5% for suspected sepsis, and 75.0% for other infectious diseases. Among 22 bacteria separated from patients with sepsis, 78.6% (11/14 strains) were eradicated by this treatment. This protocol was also effective in 57.1% (8/14) of patients whose granulocyte count was less than 100/mm3 during the course of treatment as well as in 83.3% (15/18) of patients with granulocyte count over 500/mm3. There was no difference in effectiveness between those patients to whom G-CSF was administered and those to whom it was not (17/24, 70.8% vs 35/48, 72.9%). As an adverse reaction, a transient increase of GOT and/or GPT was observed in 2 patients (2.8%). The consecutive administration treatment of FOM and SBT/CPZ is thus an effective and safe regimen for the treatment of patients with hematological diseases complicated by severe infections.
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PMID:[A combined consecutive therapy with fosfomycin and sulbactam/cefoperazone for bacterial infections associated with hematological diseases]. 754 Feb 19

Peripheral blood stem cells (PBSC) were collected from 24 patients who were treated with high dose etoposide. Studied patients included one with acute lymphoblastic leukemia, 4 with acute myeloid leukemia (AML), 1 with myelodysplastic syndrome, 13 with lymphoma, 1 with malignant histiocytosis, 2 with myeloma, and 4 with testicular tumor. Etoposide was infused at a dose of 500 mg/m2 for 4 days, followed by subcutaneous injection of recombinant human granulocyte-colony stimulating factor from the nadir of leukocyte. PBSC were collected by processing 15-20 liters of blood apheresis in the recovery phase of chemotherapy. In all patients, the number of CFU-GM collected per aphereresis ranged from 0.01 to 59.4 x 10(5)/kg, and more than 5 x 10(5)/kg CFU-GM were collected in 19 of the patients (73%). All leukemia patients treated along with our protocols have remained in complete remission, but one patient with AML relapsed within 1 month after the treatment. Ten lymphoma patients were assessable for antitumor effect, and complete response (CR) was observed in 2, partial response (PR) was 7, and no change (NC) in one patient. Two patients with myeloma were classified to be NC. Three of the 4 patients with testicular tumor were PR, and the other one was NC. Eleven patients subsequently underwent PBSCT. The number of days required to achieve an absolute granulocyte count of 0.5 x 10(9)/l was 7 to 11 days, with a mean of 8.6.
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PMID:[Peripheral blood stem cell collection with high dose etoposide]. 754 Feb 21

It is generally assumed that using high whole blood flow rates (WBFR), 80 ml/min, during peripheral blood stem cell (PBSC) collection on the Fenwal CS 3000 Plus blood cell processor will result in higher yields of mononuclear cells (MNC) than using lower WBFR (50 ml/min). To test this assumption, we retrospectively studied 129 PBSC procedures on 17 patients in a multiple myeloma protocol comparing MNC yield, as well as red blood cell (RBC), granulocyte, and platelet (Plt) content, of four average WBFR groups. Standard PBSC procedures were performed using modified procedure 1, interface offset 100, anticoagulant (AC) ratio of 11:1, small volume collection chamber, and a processing time of 4 hours. After correcting for AC volume used, the volume processed was divided by 240 minutes to obtain the average WBFR. WBFRs were separated into 4 groups of 40-49, 50-59, 60-69, and 70-79 ml/min. When compared to the highest flow rate group (70-79 ml/min), the three lower flow rate groups had significantly higher MNC yields of 16.2 +/- 6.9, 13.1 +/- 5.1, and 11.5 +/- 4.7 x 10(9), respectively, as compared to 8.9 +/- 6.1 x 10(9) MNC for the 70-79 ml/min group. There was no significant difference in granulocyte yield which ranged from 1.6 +/- 2.1 to 4.5 +/- 4.8 x 10(9).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of whole blood flow rates on mononuclear cell yields during peripheral blood stem cell collection using Fenwal CS 3000 Plus. 754 3

Since rising serum lactate dehydrogenase (LDH) heralds progression in patients with lymphoma or myeloma we investigated the significance of its elevations during chemotherapy supported by granulocyte (G-) or Granulocyte-Macrophage (GM-) colony stimulating factors (CSF). To Exclude effects of resistant disease we analyzed 52 courses of therapy in 36 responding patients. During hematologic recovery LDH increased above normal in 53% and 85% of patients with leukocyte counts of 10,000/microL and 15,000/microL, respectively. After CSF discontinuation LDH fell to or towards normal during 20 courses with adequate follow-up. Therefore rising serum LDH in patients with lymphoma or myeloma may be caused the CSF administration during chemotherapy and not by progressive disease. Proper identification of this effect can prevent unnecessary tests or treatment delays.
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PMID:Rising serum lactate dehydrogenase often caused by granulocyte-or Granulocyte-macrophage colony stimulating factor and not tumor progression in patients with lymphoma or myeloma. 754 40

In this study the leukocyte alkaline phosphatase (LAP) score in 106 patients with multiple myeloma (MM) in various phases of the disease (66 at diagnosis, 18 in plateau phase, 22 in relapse) was examined and compared with the score of 68 patients with monoclonal gammopathy of undetermined significance (MGUS) and 53 normal volunteers. In addition, the circulating levels of granulocyte-colony stimulating factor (G-CSF) were measured to explore the possible involvement of this cytokine in the pathogenetic mechanisms that lead to increased LAP activity. The results showed that the mean LAP score in patients with MGUS was comparable to normals and significantly lower than in MM (p < 0.001). Also, it increased with increasing tumor mass, and was lower in myelomas with stable disease than in those with active disease. G-CSF concentrations closely mirrored the behaviour of LAP score (r = 0.850, p < 0.001), significantly differing between each group of individuals. Its mean levels in MGUS were comparable to those of controls, whereas they were significantly increased in MM (p < 0.001), again with escalating values from cases with low tumor mass to advanced stages, and with lower concentrations in patients in plateau phase than in those in relapse. A significant correlation was found between G-CSF and neopterin levels (r = 0.578, p < 0.001), thus indicating an origin of the cytokine from monocytes and macrophages. These findings suggest that LAP scoring may assist in distinguishing benign from malignant paraproteinemias and may be used to follow the progression of plasma cell neoplasias.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Leukocyte alkaline phosphatase score in plasma cell dyscrasias: correlation with disease severity and circulating levels of granulocyte-colony stimulating factor. 754 41

Monocyte chemoattractant protein-1 (MCP-1) belongs to the newly recognized "chemokine" superfamily of activation-inducible cytokines. We report here that MCP-1 gene-transferred mouse myeloma cells modulate tumor necrosis in myeloma-bearing nude mice. We established an MCP-1-producing myeloma cell line (X63-MCP-1) by transfection with human MCP-1 cDNA as well as interleukin-8-producing X63 cells (X63 IL-8). Each cell line showed the same growth characteristics in vitro, and 1 x 10(7) cells per mouse were injected into the peritoneal cavity resulting in the formation of tumors. Hematologic studies, including peripheral white blood cell counts and differentiation, showed no differences among the groups. They formed tumors in the same manner, which we observed from weeks 2.5 to 9. MCP-1 mice showed more tumor necrosis and infiltration of the macrophages into the tissue surrounding the tumor. In situ hybridization, using a partial cDNA as a probe, showed that macrophages contained MCP-1 mRNA. Bone marrow cell colony-forming assay showed a greater number of both granulocyte and macrophage colonies in MCP-1 mouse femur than in those of controls or interleukin-8 mice. MCP-1 has no direct stimulatory activity on stem cells, but longer exposure to MCP-1 in vivo might stimulate both granulocyte and macrophage progenitors and recruitment of macrophages into tumors, and it might explain the antitumor activity of macrophages in tumor-bearing nude mice.
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PMID:Monocyte chemoattractant protein-1 stimulates tumor necrosis and recruitment of macrophages into tumors in tumor-bearing nude mice: increased granulocyte and macrophage progenitors in murine bone marrow. 763 82

We reported the experience of peripheral blood stem cell transplantation (PBSCT) performed in adult patients with hematological malignancies and solid tumors. After myelosuppressive chemotherapy, peripheral blood stem cells were collected using a Blood Cell Separator (CS-3000) during bone marrow recovery and subsequently cryopreserved in 17 patients (9: malignant lymphoma; 2: ALL; 2: AML; 2: multiple myeloma; 2: solid tumors). In 28 apheresis cases, the collected number of granulocyte/macrophage progenitors (CFU-GM) was more than 5 x 10(5)/kg BW in 17 apheresis cases and ranged between 2 and 5 x 10(5)/kg BW in 4 of such cases. Eleven patients (7: malignant lymphoma; 1: ALL; 1: AML; 1: multiple myeloma; 1: neuroblastoma) underwent PBSCT following myeloablative chemotherapy. The infused number of CFU-GM ranged between 0.6 and 18.1 x 10(5)/kg BW. In 7 patients, more than 5 x 10(5) CFU-GM/kg BW were infused. The median time to reach 500 neutrophils/microliter or 50,000 platelets/microliter was 10 (range: 8-17) and 20 (range: 8-63) days, respectively. One patient died from sepsis before hematologic recovery occurred. Eight patients are alive with no evidence of active disease for 7-19 months after PBSCT. When the infused number of CFU-GM is more than 2 x 10(5)/kg BW, PBSCT following myeloablative chemotherapy seems to be safe and useful treatment.
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PMID:[Peripheral blood stem cell transplantation in adult patients]. 768 Aug 48

Interleukin-4 (IL-4), originally identified as a B-cell growth factor, has been shown to inhibit certain stages of hematopoietic stem cells. Recently, IL-4 has been recognized as a negative regulatory factor in the growth of hematologic malignancy. In myeloid leukemias, IL-4 can suppress the growth of growth factor-dependent leukemic blast cells derived from acute myelogenous leukemia (AML). IL-4 also suppresses the growth of chronic myelomonocytic leukemia cells through inhibiting the "autocrine" production of IL-6 or granulocyte/macrophage colony-stimulating factor. In lymphoid malignancies, IL-4 can inhibit the proliferation of neoplastic cells from Ph1-positive acute lymphoblastic leukemia, non-Hodgkin's B-cell lymphoma, and multiple myeloma. Thus, IL-4 is expected to be useful as a therapeutic agent for these hematologic malignancies.
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PMID:The role of interleukin-4 in the negative regulation of leukemia cell growth. 768 64


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