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)

In the present study the gene expression of cytokines promoting in vitro myeloma-cell growth was investigated by Northern blot analysis using total RNA of 36 tumour samples of patients with multiple myeloma (MM) or plasma cell leukaemia and poly(A)+ RNA of 10 human myeloma cell lines (HMCL). These cytokines included interleukin (IL)-1 alpha, IL-1 beta, IL-3, IL-6, granulocyte-macrophage (GM)-colony-stimulating factor (CSF) and granulocyte (G)-CSF. IL-1 beta, IL-6 and G-CSF genes were coexpressed in most patients, although at variable levels. IL-1 alpha transcripts were detected in 32% of patients in whom coexpression of IL-1 beta gene was found. IL-3 gene was not expressed in patients' cells and GM-CSF mRNA was detected in only 1/32 patients. No detectable transcripts for the above cytokines were present in HMCL, whereas IL-6 gene was expressed in 2/10 HMCL. We also looked for the presence of transcripts for IL-2, leukaemia inhibitory factor (LIF) and transforming growth factor (TGF)beta in cells of tumour samples from the same patients and in HMCL. IL-2 gene was not expressed in MM patients and HMCL. Weak expression of LIF gene was detected in three patients (9%), and transforming growth factor beta (TGF beta) mRNA was observed in 12/12 tumour samples analysed and all HMCL. These results suggest that, among cytokines shown to control myeloma-cell growth in vitro, IL-1, IL-6 and G-CSF could play a role in the development of myeloma disease in vivo.
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PMID:Cytokine gene expression in human multiple myeloma. 751 Sep 89

Starting from May, 1991, 35 untreated myeloma patients entered a multicentric pilot study to evaluate the feasibility of a program of PBSC transplantation for previously untreated myeloma patients. The schedule was as follows: 2 cycles of VAD followed by CY, 7 g/mq+G-CSF (Granulokine, Roche) for 14 days, to increase and collect PBSC. The subsequent conditioning regimen was Melphalan+Busulfan followed by G-CSF. As maintenance R alpha-2 IFN was given, until relapse. The median follow-up is 14 months (4-22). On April 1993, 34 patients received at least 2 cycles of VAD, 27 were submitted to PBSC collection, 22 received conditioning regimen plus PBSC and 16 of them are in the maintenance treatment with IFN. Considering 28 patients for an intention to treat evaluation (35-7 in treatment), responding patients are 71% with 46% who achieved CR. White cells and platelets raised to > 1000/mmc and > 50,000/mmc after a median period of 10 and 13 days, from CY, and 11 and 14 days from transplant, respectively. Two patients relapsed, 2 others died while in PR because of CMV epatitis and candida pneumonia. The median number of CD34+ cells and CFU-GM was 24.75 x 10(6)/kg b.w. and 28.1 x 10(4)/kg b.w. respectively. In conclusion this treatment seems to be feasible and with low toxicity, but a longer follow-up is needed to evaluate the progression free survival of the high proportion of responding patients that we observed.
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PMID:Treatment of multiple myeloma with autologous blood stem cell transplantation. Preliminary results of an Italian multicentric pilot study. 751 17

The presence of primitive hematopoietic progenitor cells or stem cells in peripheral blood (PBSC's) harvests was investigated in a single cell culturing assay and compared with the results obtained in aspirates of normal bone marrow. Based on the presence of CD33, rather differentiated progenitor cells (CD34+/33+) were distinguished from more primitive cells (CD34+/33-). The growth potential of CD34+/33+ and CD34+/33- cells have been studied. Single cell sorting was performed from peripheral blood harvests, obtained from three patients with multiple myeloma during hematopoietic recovery after treatment with high dose cyclophosphamide and rhu-GM-CSF. To test the effect of "stem cell recruiting factors" the cells were sorted in 96-well plates, prefilled with liquid medium both in the presence of IL-3 + G-CSF+GM-CSF+Epo and the same growth factors supplemented with SCF+IL-6. Addition of SCF and IL-6 to the culturing medium enhanced the plating efficiency of CD34+/33- cells considerably more than that of CD34+/33+ cells. This was observed in harvests of peripheral blood as well as in aspirates of normal bone marrow. The differences between CD34+/33+ and CD34+/33- were even more pronounced when only the large colonies (> 500 cells/well) were taken into consideration. Assuming that IL-6 and SCF are "stem cell recruiting factors," the CD34+/33- fraction contains more clonogenic cells than the CD34+/33+ fraction. In all three patients the first CD34+ cells appearing in the peripheral blood (PB) after cytoreductive treatment were predominantly CD34+/33- (> 80%). At later stages when the leukocyte counts had reached higher values the CD34+/33+ cells predominated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Peripheral blood cell harvests yield primitive multilineage progenitor cells in the CD34+/33- fraction. 751 21

In order to assess the contamination with malignant cells of peripheral blood stem cell (PBSC) transplants used to support high-dose therapy in multiple myeloma (MM), we used the immunoglobulin heavy chain gene radioactive fingerprinting polymerase chain reaction (PCR) method to detect clonal cells in PBSC from 10 patients. The sensitivity of the technique allowed the detection of one clonal cell among 10(4) normal blood mononuclear cells. A clonal band was detected in 4 of 11 leukaphereses samples. The level of contamination was low because a clonal band could never be identified on ethidium bromide-stained agarose gels whose sensitivity is between 1 and 5%. The use of granulocyte-colony stimulatory factor (G-CSF) in combination with chemotherapy in three cases did not seem to increase the contamination of PBSC grafts; in one patient, G-CSF was used during a second course of leukapheresis which was free of detectable clonal cells whereas the first one performed after chemotherapy alone contained clonal cells. Thus, PBSC grafts may rarely be completely devoid of clonal potentially malignant cells but the level of contamination is much lower than in BM grafts. Whether graft contamination is an important adverse prognostic factor for patients with MM undergoing intensive treatment and autografting is still unsettled.
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PMID:Myeloma cell contamination of peripheral blood stem cell grafts in patients with multiple myeloma treated by high-dose therapy. 752 6

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

The change in phenotype, number and proliferative capacity of peripheral blood hematopoietic progenitors (PBHP) was studied in six patients with multiple myeloma during hematopoietic recovery after mobilization with high-dose cyclophosphamide and GM-CSF or G-CSF. In all six patients the first CD34+ cells appearing in the peripheral blood (PB) after cytoreductive treatment were predominantly CD34+/33- (> 70%). At later stages when leukapheresis procedures were started, the CD34+/33+ cells predominated in five of six patients. In leukapheresis harvests of peripheral blood, and in bone marrow addition of SCF and IL-6 to the culturing medium enhanced the plating efficiency. In peripheral blood an increase from 12 to 22% for CD34+/33+ and from 6 to 14% for CD34+/33- was observed. In normal bone marrow we observed an increase from 15 to 23% for CD34+/33+ and from 7 to 17% for CD34+/33-. Highly proliferative progenitors (>500 cells) in the CD34+/33- fraction appeared to be dependent on the addition of 'stem cell recruiting factors' (SCF and IL-6); in bone marrow the percentage of wells with >500 cells increased from 0.9 to 12.6% after SCF+IL-6 and in PBHP from 2 to 9%. We conclude that the first progenitors appearing in the peripheral blood after priming with high-dose cyclophosphamide and GM- or G-CSF have a more primitive immunophenotype, CD34+/33-.
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PMID:Primitive multilineage progenitor cells predominate in peripheral blood early after mobilization with high-dose cyclophosphamide and GM-CSF or G-CSF. 752 61

In this study we investigated the proliferation of three well-documented MM lines and 10 bone marrow samples from myeloma patients in response to rh-SCF alone and combined with Interleukin-6 (IL-6), IL-3 and IL-3/GM-CSF fusion protein PIXY 321. Neoplastic plasma cells were highly purified (> 90%) by immunomagnetic depletion of T, myeloid, monocytoid and NK cells. The number of S-phase cells was evaluated after 3 and 7 d of liquid culture by the bromodeoxyuridine (BRDU) incorporation assay. The proliferation of RPMI 8226 and U266 cell lines was also assessed by a clonogenic assay. All the experiments were performed in serum-free conditions. RPMI 8226 cell line was not stimulated by SCF which also did not augment the proliferative activity of IL-6, IL-3 and PIXY-321. Conversely, SCF addition resulted in 2.4-fold increase of the number of U266 colonies and in a higher number of U266 and MT3 cells in S-phase (24.5 +/- 2% SEM v 14.5 +/- 1% SEM and 32 +/- 3% SEM v 21 +/- 4% SEM, respectively; P < 0.05). The c-kit ligand also enhanced the proliferation of MT3 and U266 cells mediated by the other cytokines. Anti-SCF polyclonal antibodies completely abrogated the proliferative response of MT3 cells to exogenous SCF and markedly reduced the spontaneous growth of the same cell line. Reverse transcriptase-polymerase chain reaction amplification (RT-PCR) did detect SCF mRNA in MT3 and RPMI 8226 cells. Moreover, secreted SCF was found, in a biologically active form, in the supernatant of the two cell lines by the MO7e proliferation assay. When tested on fresh myeloma samples, SCF increased the number of S-phase plasma cells (4.7 +/- 1.6% v 3.4 +/- 1.3% in control cultures: P = 0.02). Significant proliferation was also induced by IL-6 (7 +/- 2.3% of BRDU+ cells; P = 0.006), IL-3 (5.3 +/- 1.3%; P = 0.01) and PIXY-321 (5.4 +/- 1.6%; P = 0.02). The addition of SCF significantly enhanced the proliferation of myeloma cells responsive to IL-6. In summary, our results indicate that SCF is expressed in MM cells and stimulates the proliferation of neoplastic plasma cells.
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PMID:Expression and functional role of c-kit ligand (SCF) in human multiple myeloma cells. 752 40

Colony-stimulating activity (CSA) was measured by the production of granulocyte-macrophage colony-forming units (GM-CFU) from normal donor bone marrow in the plasma of 29 patients with multiple myeloma (MM) after intensive treatment with high-dose melphalan (HDM) with or without autologous bone marrow rescue (ABMR). Although patients who received ABMR had an earlier recovery of circulating neutrophils compared with those who received HDM alone, the time at which CSA reached a maximum was similar in both groups (10 to 11 days) after therapy. The decline in CSA correlated with the recovery of the neutrophil count. In plasma from patients who received recombinant human granulocyte colony-stimulating factor (rhG-CSF), in addition to an autograft, CSA reached a maximum earlier (7 days). Furthermore, neutrophil recovery was earlier in these patients. Platelet recovery was not increased by rhG-CSF. The time at which CSA was maximum in four patients who were undergoing intensive therapy for the second time occurred 9 days after treatment with HDM. Although the period without neutrophils was longer in three (of four) patients who survived long term, one patient who received rhG-CSF had a shorter period of neutropenia than the two who had not had the cytokine. G-CSF was detected in plasma from seven of seven patients but not at all times after treatment. In plasma samples that contained G-CSF, colony numbers were increased by recombinant interleukin-4 (rIL-4) in vitro. Neither IL-3 nor GM-CSF was detected in plasma; however, antibody to GM-CSF reduced CSA in all samples after intensive therapy. The data suggest that CSA is a consistent physiologic response to intensive therapy, even in previously treated patients, but that hematologic recovery is dependent on the availability of viable progenitor cells.
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PMID:G-CSF is a major component of colony-stimulating activity (CSA) in the plasma of patients with multiple myeloma after treatment with high-dose melphalan (HDM). 753 16

Recombinant human granulocyte colony stimulating factor (rHuG-CSF) has been used for several years in clinical haematology and it is now routinely employed to prevent or treat chemotherapy-induced neutropenia. rHuG-CSF is also administered after autologous or allogeneic bone marrow transplantation (BMT), since it can significantly shorten the duration of neutropenia. However, probably its main use at the moment is to facilitate the collection of peripheral blood stem cells (PBSC) from patients with lymphoma, myeloma and breast cancer. Within controlled trials, it is also used as an adjunct to immunosuppression for patients with aplastic anaemia. rHuG-CSF has a number of other potential uses such as increasing the numbers of progenitor cells for transplantation by in vivo and/or ex vivo amplification; treatment of non-neutropenic infections post transplant, and prophylaxis and treatment of cytomegalovirus infections. In the future, autologous stem cell transplants may be performed in the outpatient department thus expanding the use of PBSC transplantation to disease areas not previously considered suitable for such myelosuppressive treatment.
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PMID:The clinical benefits of recombinant human granulocyte colony stimulating factor in the treatment of cancer patients. 753 69

Peripheral blood progenitor cells (PBPC) can be mobilized using cytotoxic chemotherapy and cytokines. There is a substantial variability in the yield of hematopoietic progenitor cells between patients. We were looking for predictive parameters indicating a patient's response to a given mobilization regimen. Multiparameter flow-cytometry analysis and clonogenic assays were used to examine the hematopoietic progenitor cells in bone marrow (BM) and peripheral blood (PB) before filgrastim (R-metHuG-CSF; Amgen, Thousand Oaks, CA)-supported chemotherapy and in PB and leukapheresis products (LPs) in the recovery phase. Fifteen patients (four with high-grade non-Hodgkin's lymphoma [NHL], two with low-grade NHL, two with Hodgkin's disease, two with multiple myeloma, three with breast cancer, one with ovarian cancer, and one with germ cell tumor) were included in this study. The comparison of immunofluorescence plots showed a homogenous population of strongly CD34+ cells in steady-state and mobilized PB whereas in steady-state BM, the CD34+ cells ranged from strongly positive with continuous transition to the CD34- population. Consistent with the similarity in CD34 antigen expression, a correlation analysis showed steady-state PB CD34+ cells (r = .81, P < .001) and colony-forming cells (CFCs; r = .69, P < .01) to be a measure of a patient's mobilizable CD34+ cell pool. Individual estimates of progenitor cell yields could be calculated. With a probability of 95%, eg, 0.4 steady-state PB CD34+ cells x 10(6)/L allowed to collect in six LPs 2.5 x 10(6) CD34+ cells/kg, the reported threshold-dose of progenitor cells required for rapid and sustained engraftment after high-dose therapy. For the total steady-state BM CD34+ cell population, a weak correlation (r = .57, P < .05) with the mobilized CD34+ cells only became apparent when an outlier was removed from the analysis. Neither the CD34+ immunologic subgroups defined by the coexpression of the myeloid lineage-associated antigens CD33 or CD45-RA or the phenotypically primitive CD34+/HLA-DR- subset nor the BM CFC count had a predictive value for the mobilization outcome. This may be caused by the additional presence of maturing progenitor cells in BM, which express lower levels of the CD34 antigen and do not circulate. Our results permit us to recognize patients who are at risk to collect low numbers of progenitor cells and those who are likely to achieve sufficient or high progenitor cell yields even before mobilization chemotherapy is administered.
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PMID:Peripheral blood progenitor cell (PBPC) counts during steady-state hematopoiesis allow to estimate the yield of mobilized PBPC after filgrastim (R-metHuG-CSF)-supported cytotoxic chemotherapy. 860 80


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