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)

A young Italian woman with a POEMS syndrome is described. The patient had a plasma cell dyscrasia without clinical or laboratory evidence of multiple myeloma. The phenotypic analysis of bone marrow cells and peripheral blood lymphocytes revealed a normal pattern. The immunological study of CSF showed high levels of interleukin-6, whereas this cytokine was not detectable in the serum. Electrophysiological studies and sural nerve biopsy showed a mixed, demyelinating-axonal sensorimotor neuropathy with marked loss of large myelinated fibres. Long-term treatment with prednisone gave some clinical improvement.
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PMID:POEMS syndrome: clinical, pathological and immunological study of a case. 770 42

Forty six patients with lymphoid malignancies receiving autologous transplants using three different sources of hematopoietic stem cells were compared for engraftment parameters. Thirteen patients (five with multiple myeloma, seven with non-Hodgkin's lymphoma and one with Hodgkin's lymphoma) received autologous marrow with post-transplant growth factors (group 1). During the same time interval, 14 patients (five with multiple myeloma, six with non-Hodgkin's lymphoma and three with Hodgkin's lymphoma) were transplanted with autologous marrow plus recombinant granulocyte colony-stimulating factor (rhG-CSF)-mobilized peripheral blood stem cells (PBSC) and post-transplant growth factors (group 2). Nineteen patients (seven with multiple myeloma and 12 with non-Hodgkin's lymphoma) received rhG-CSF mobilized PBSC and post-transplant growth factors (group 3). All PBSC were collected after G-CSF mobilization (16 micrograms/kg/day s.c. for 6 days) without prior chemotherapy. After high-dose myeloablative chemotherapy or chemoradiotherapy, the median days to recovery of neutrophils to levels of 0.5 and 1.0 x 10(9)/l were 12 vs. 9 vs. 9 days (P = 0.0003 (group 1 vs. group 2) and P = 0.53 (group 2 vs. group 3)) and 13 vs. 10 vs. 10 days (P = 0.0003 (group 1 vs. group 2) and 0.92 (group 2 vs. group 3)) for groups 1, 2 and 3, respectively. The median day to platelet transfusion independence was 22 vs. 11 vs. 11 days (P = 0.001 (group 1 vs. group 2) and P = 0.50 (group 2 vs. group 3)) for groups 1, 2 and 3, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Engraftment of patients with lymphoid malignancies transplanted with autologous bone marrow, peripheral blood stem cells or both. 777 13

This prospective open trial evaluated the efficacy and tolerability of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in patients with established neutropenia, considering as the main endpoint the clinical benefit to the patients regarding clearing of infection or resuming chemotherapy as initially planed. Adult patients (n = 28) with absolute neutrophil counts (ANC) < 10(9)/1 for 21 days were given a fixed dose (400 micrograms) of rhGM-CSF subcutaneously, for a total of 35 cycles. Causes of neutropenia were chemotherapy for acute leukaemia, lymphoma, myeloma and solid tumours, complications after bone marrow transplantation (BMT), and neutropenia associated with AIDS. Response (ANC to > 10(9)/l) occurred in 83% of rhGM-CSF cycles (29/35). Median time to response was 2.4 days (mean 6.7 days). Kinetics of response was dependent on diagnosis and treatment history. Fever abated with increasing ANC in 13/17 patients (76%) who entered the trial with hyperpyrexia. Treatment with rhGM-CSF allowed chemotherapy to be resumed on schedule in 7/9 relevant cycles. Toxicity was mild, leading to treatment interruption in only two cycles. In conclusion, rhGM-CSF was well tolerated and associated with a rise in ANC which appeared to result in immediate clinical benefit, including resolution of infection and resumption of scheduled chemotherapy.
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PMID:Recombinant human granulocyte-macrophage colony-stimulating factor in acquired or chemotherapy-induced neutropenia. An open clinical trial. 794 41

The pharmacokinetics of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF), induction of anti-GM-CSF antibodies, and clinical effects related to the induction of the antibodies were analyzed in patients with metastatic colorectal carcinoma (CRC) who were not on chemotherapy (n = 20, nonimmunocompromised patients). rhGM-CSF (250 micrograms/m2/d; Escherichia coli-derived) was administered subcutaneously for 10 days every month for 4 months. Eight patients with multiple myeloma (MM) on intensive chemotherapy followed by rhGM-CSF treatment were also included (immunocompromised patients). After a single injection of GM-CSF at the first cycle in CRC patients, the maximum calculated concentration (Cmax) was 5.24 +/- 0.56 ng/mL; the half life (T1/2) was 2.91 +/- 0.8 hours; and the area under the concentration curve (AUC) was 30.86 +/- 6.03 hours x ng/mL (mean +/- SE). No anti-GM-CSF antibodies were detected. During the subsequent cycles, 95% of the CRC patients developed anti-GM-CSF IgG antibodies, which significantly altered the pharmacokinetics of rhGM-CSF at the third and fourth cycles with decreased Cmax (2.87 +/- 0.57 ng/mL; P < .05), T1/2 (1.57 +/- 0.2 hours; P < .05), and AUC (14.90 +/- 4.10 hours x ng/mL; P < .005). The presence of anti-GM-CSF antibodies significantly reduced the GM-CSF-induced enhancement of granulocytes, and there was a clear tendency for a decreased increment of monocytes. Antibodies diminished systemic side effects of rhGM-CSF. Only 1 of 8 MM patients showed a very low anti-GM-CSF antibody titer after GM-CSF therapy, as shown by enzyme-linked immunosorbent assay and Western blot. Therefore, in nonimmunocompromised patients, exogenous nonglycosylated GM-CSF induced an anti-GM-CSF IgG antibody response in practically all patients, which seemed to be of clinical significance. In immunocompromised patients, virtually no significant antibody response was shown.
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PMID:Induction of anti-recombinant human granulocyte-macrophage colony-stimulating factor (Escherichia coli-derived) antibodies and clinical effects in nonimmunocompromised patients. 799 26

High-dose cyclophosphamide (HD-CY; 7 g/m2) was administered to patients suffering from high risk multiple myeloma (MM). The safety of this procedure, the recirculation and collection of peripheral blood stem cells (PBSC) and the effect of rhGM-CSF and HD-CY were studied. Group I patients (n = 21) were treated with HD-CY alone. Group II patients (n = 10) received 5 micrograms/kg/day rhGM-CSF iv after HD-CY. Neutropenia was shorter in group II (p = 0.01). In group II, the number of circulating colony forming units (CFU-GM) after 14 days was correlated with the number of circulating CFU-GM after 7 days (r = 0.85, p < 0.0001) and with the number of CD34+ cells (r = 0.839, p = 0.01). The total number of mononuclear cells (MNC) and CFU-GM collected per patient was two and seven-fold higher, respectively, in group II (p = 0.01 and p = 0.03). Recovered MNC and CFU-GM were 1.7 and 7-fold higher, respectively, in group II (p = 0.01 and p = 0.004). Our data show that HD-CY is an efficient means of collecting functional PBSC in MM. We suggest that rhGM-CSF is able to further enhance this yield in MM.
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PMID:Collection of peripheral blood stem cells in multiple myeloma following single high-dose cyclophosphamide with and without recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). 810 70

We report a novel, reproducible methodology which enabled 10 human myeloma cell lines (HMCL) to be obtained from each of 10 tumor samples harvested from 9 patients with extramedullary proliferation. Fresh samples were cultured with interleukin 6 (IL-6) and granulocyte macrophage-colony stimulating factor (GM-CSF) at a high cell density and resulting HMCL growth became progressively dependent on IL-6 alone, no longer requiring GM-CSF. These HMCL, which had the same immunoglobulin gene rearrangements as the patients' original myeloma cells, were designated XG-1 to XG-9. XG HMCL had a plasma cell morphology, expressed plasma cell antigen (Ag), namely cytoplasmic immunoglobulins, CD38, B-B4 Ag, and CD77, and lacked the usual B-cell Ag. They also expressed activation antigens such as CD28 with coexpression of CD28 and its ligand, B7 Ag, in four HMCL. Six HMCL expressed CD40, 4 CD23, and 5 its ligand, CD21. The XG HMCL bore adhesion molecules VLA-4 and CD44 (all 10 HMCL), VLA-5 (7 HMCL), and CD56 (4 HMCL). Finally, cytogenetic study of 8 HMCL indicated a 14q+ chromosome, and t(11,14) translocation was found in 6 of 8 and 5 of 8 HMCL, respectively. The possibility of obtaining malignant plasma cell lines reproducibly from each patient with extramedullary proliferation offers a unique tool for studying the phenotype and abnormalities of the still unidentified tumor stem cell in this disease.
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PMID:Reproducible obtaining of human myeloma cell lines as a model for tumor stem cell study in human multiple myeloma. 820 90

Twenty-four patients with multiple myeloma (MM), three (12.5%) in complete remission (CR) and 21 (87.5%) in partial remission (PR) were treated with high-dose chemotherapy (HDCT) (busulfan 12 mg/kg+melphalan 140 mg/m2) as preparative regimen for autologous peripheral blood stem cell (PBSC) transplantation. These cells were previously collected by leukapheresis after mobilization by high-dose cyclophosphamide (HD Cy)+rhGM-CSF (18 patients) or rhG-CSF alone (six patients). Considering 23 evaluable patients following HDCT, the CR rate was 58% (14 patients) and the PR rate was 38% (nine patients). One transplant-related death occurred following this regimen (4%). With a median follow-up of 20 months (range 4-34) after transplantation, 21 patients are alive (87%). Disease progression after transplantation was observed in four patients. Overall and relapse-free actuarial survival at 24 months was 91% and 74%, respectively. 12 patients (50%) remain in CR 15 months (4-34) post transplant. The major toxicity was mucositis. Busulfan+melphalan is a safe and feasible conditioning regimen for APBSCT in MM with acceptable toxicity and a high objective response rate, which may result in prolonged survival.
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PMID:Busulfan and melphalan as conditioning regimen for autologous peripheral blood stem cell transplantation in multiple myeloma. 854 79

Haemopoietic recovery is more rapid after peripheral blood stem cell (PBSC) transplantation than after autologous bone marrow transplantation, and the aim of this study was to assess the role of the large number of lymphocytes and monocytes (accessory cells) in a PBSC leukapheresis product in this rapid regeneration. Haematological recovery was therefore assessed in 10 PBSC recipients with lymphoma or myeloma in whom monocytes and T cells were depleted by a median of 2.3 and 3.3 logs by CD34+ cell selection using the CEPRATE SC stem cell concentration system and compared with recovery in 59 recipients who received whole PBSC. After allowing for the number of progenitor cells reinfused, there was no significant delay in engraftment induced by accessory cell depletion. Plasma levels of granulocyte-colony stimulating factor (G-CSF), granulocyte/monocyte-colony stimulating factor (GM-CSF), interleukin-6 (IL-6), stem cell factor (SCF) and macrophage-inhibition factor-alpha (MIP-1-alpha) during the transplant procedure were similar whether or not accessory cells were given. The G-CSF and IL-6 levels rose between days 5 and 14 post transplantation to approximately 1 ng/ml and 50 pg/ml respectively. This study indicates that accessory cells reinfused with PBSC collections are not responsible for the subsequent cytokine profile or rapid haematological recovery.
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PMID:Accessory cells do not contribute to G-CSF or IL-6 production nor to rapid haematological recovery following peripheral blood stem cell transplantation. 855 91

Three major molecules have been recognized as IgE-binding structures on hematopoietic cells: the heterotrimeric high-affinity receptor for IgE (Fc epsilon RI), the low-affinity receptor for IgE (Fc epsilon RII/CD23) and the Mac-2/IgE-binding protein (epsilon BP). The latter has been shown to be expressed on polymorphonuclear neutrophils (PMN), where it regulates IgE-dependent activation. Experiments were undertaken to determine whether the IgE-binding capacity of PMN is mediated exclusively by this molecule. No detectable binding of human myeloma IgE to unstimulated PMN from normal volunteers could be evidenced. In contrast, PMN stimulated with granulocyte macrophage colony stimulating factor (GM-CSF) (500 U/ml) for 24 h displayed positive IgE binding. This binding was significantly inhibited in the presence of mAb directed against Mac-2/epsilon BP and also in the presence of anti-CD23 mAb, but not of anti-Fc epsilon RI mAb or isotype-matched controls. By flow cytometry, CD23 expression was detected on GM-CSF-primed PMN by several anti-CD23 mAb, including EBVCS-5, BB10 or Mab135, which recognize different epitopes. CD23 was also evidenced by immunocytochemistry in GM-CSF-primed PMN. By in situ hybridization, GM-CSF-treated PMN exhibited a hybridization signal for CD23 mRNA and the presence of the CD23b isoform-specific mRNA was detected by RT-PCR. These findings indicate that PMN can synthesize CD23 molecules under GM-CSF induction. This strong CD23 expression might be of physiopathological relevance in IgE-dependent activation during allergic processes.
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PMID:Granulocyte macrophage colony stimulating factor induces Fc epsilon RII/CD23 expression on normal human polymorphonuclear neutrophils. 872 38

The methods of mobilization and collection of stem cells in peripheral blood stem cells transplantation (PBSCT) and the association between the number of stem cells transplanted and hematopoietic recovery were studied. The investigation was carried in 22 patients (11 acute leukemia, 6 multiple myeloma, 4 non-Hodgkin's lymphoma, 1 breast cancer). Three regimens for mobilization were carried out as follows: 1) chemotherapy + tetrahydrofolic acid + dexamethasone, 2) chemotherapy + rhGM-CSF + dexamethasone, 3) chemotherapy + rhG-CSF + dexamethasone. Besides, CD34/CD33 dual-color direct immunofluorescence flow cytometry assay was performed in 7 cases in the rhG-CSF group. The results showed: 1) The mean number of collected cells (MNC) in the rhG-CSF group was MNC (8.29 +/- 6.14) x 10(8)/kg and CFU-GM (21.35 +/- 17.24) x 10(4)/kg, being highest among the 3 groups. 2) The number of CD34+ cells correlated with MNC and CFU-GM. CD34+ cells in the peripheral blood were 0 or < 0.5% before mobilization and increased markedly 6-8 days after rhG-CSF administration. Harvesting should be started at that time and carried out every day until CD34+ cells reached 5 x 10(6)/kg. 3) The number of PBSC transplanted was the key to hematopoietic recovery.
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PMID:[A study on the peripheral blood stem cells mobilization, collection and their effects on engraftment]. 873 24


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