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)

Despite major advances in supportive care, neutropenic infections and thrombopenic bleedings remain major lethal treatment- and disease-related complications in patients with malignancy. Moreover, complications of platelet (Plt) and erythrocyte transfusion therapy have become a cause of great concern and shortages of homologous blood products are a constant problem. Suggestions that the application of recombinant human hemopoietins may provide an alternative treatment modality in this patient population is currently being evaluated in clinical trials. Erythropoietin (EPO) has been shown to be effective in the treatment of anemia in patients with bone marrow, infiltrating low-grade non-Hodgkin's lymphoma, multiple myeloma, and in some patients with myelodysplastic syndrome. Preliminary data suggest that subcutaneous administration of EPO results in a higher slope of increasing erythropoietic parameters compared to intravenous administration. Protective effects on normal erythropoiesis have been attributed to EPO in patients receiving chemotherapy. The finding of EPO receptors on megakaryocytes supports the clinical observation of increased Plt production associated with decreased bleeding and transfusion frequencies in a substantial number of patients receiving EPO. Clinical trials with granulocyte-macrophage (GM-CSF) and granulocyte colony stimulating factor (G-CSF) have reached phase III trials. Both factors show high efficacy to shorten or improve neutropenia related to chemotherapy, bone marrow transplant, or underlying disease. Mechanisms responsible for mucosa protection and improved healing of mucositis observed with both factors remain undetermined yet phase I/II evaluation of IL-3 shows multilineage hemopoietic responses including myeloid, erythroid, and megakaryocyte lineages. Possible anti-cancer effects of hemopoietins achieved by direct action or by increased chemotherapy intensity are currently under investigation.
 ...
PMID:Hemopoietins in clinical oncology. 204 61

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.
 ...
PMID:The clinical benefits of recombinant human granulocyte colony stimulating factor in the treatment of cancer patients. 753 69

A 52-year-old man was admitted to our hospital because of oliguric renal failure. The patient was well until four weeks earlier, when he developed nausea and anorexia. The urea nitrogen was 179 mg/dl, creatinine 29.2 mg/dl, uric acid 19.0 mg/dl and potassium 8.6 mEq/1. Hemodialysis was started immediately after admission. Bone marrow aspiration showed atypical plasma cell infiltration consistent with multiple myeloma. The immunoelectrophoresis revealed urinary lambda -type Bence Jones protein and serum IgD- lambda -type M protein. The findings of renal biopsy study were consistent with myeloma kidney. On the fourth hospital day, administration of prednisolone 40 mg and melphalan 2 mg was started. The patient also underwent double filtration plasma-pheresis (DFPP). Serum IgD level was decreased from 950 to 113 mg/dl. After a course of chemotherapy, however, he developed severe leukopenia and was complicated with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. This complication was successfully treated with imipenem/cilastation and vancomycin combined with granulocyte colony stimulating factor (G-CSF). The patient was discharged and returned to work on maintenance hemodialysis. Fifteen months after the presentation, he manifested progressive peripheral nerve disturbances. Three months later, the patient died--not from renal failure, but from ventricular arrhythmia. The application of maintenance dialysis therapy to myelomatosis has until now been questioned. The present case, however, suggests that aggressive treatment consisting of chronic dialysis therapy as well as chemotherapy and plasma exchange should be administered even in patients with established renal failure.
 ...
PMID:[Maintenance hemodialysis in IgD- lambda -type multiple myeloma associated with severe renal failure]. 813 51

This study was performed to determine the factors influencing the collection of autologous peripheral blood stem cells (PBSC) in patients with multiple myeloma (MM) who had disease which had progressed after an initial response or who had refractory disease. Fifty-seven patients with MM underwent PBSC collections following recombinant human granulocyte colony stimulating factor (G-CSF) alone (n = 19) (16 micrograms/kg/day), cyclophosphamide (CY) (4 gm/m2 x 1) with either G-CSF (10 micrograms/kg/day) (n = 7) or granulocyte-macrophage colony-stimulating factor (GM-CSF) (500 micrograms/m2/day) (n = 7) or cyclophosphamide (4 gm/m2 x 1) and etoposide (200 mg/m2/day x 3) (CE) with G-CSF (10 micrograms/kg/day) (n = 24). The goal was to collect 5 x 10(6) CD34+ cells/kg. Fifty of 57 patients underwent autologous transplantation with PBSC alone (n = 39) or PBSC + marrow (n = 11). The median yield of CD34+ cells was 7 x 10(6)/kg (range 0-178.3). Thirty-nine of 57 patients (68%) achieved the target level of 5 x 10(6) CD34+ cells/kg in a median of three (range 1-8) collections. Eighteen (32%) patients yielded < 5 x 10(6) CD34+ cells/kg with the first collections. Thirteen of these 18 patients yielded < 2.5 x 10(6) and five yielded 2.5-4.95 x 10(6) CD34+ cells/kg. Of the 18 patients with less than optimal CD34+ cell yields, five with CD34+ yields of 2.5-4.95 x 10(6)/kg received PBSC alone at transplant, six underwent marrow storage to augment the PBSC dose and received PBSC plus marrow and seven patients underwent secondary collections. Of seven patients who underwent second (n = 5) or third (n = 2) cycles of PBSC collections using G-CSF 16 (n = 4) or 32 (n = 3) micrograms/kg/day, > 2.5 x 10(6) CD34+ cells/kg were collected in four patients. Two patients achieved < 0.18 CD34+ cells following three cycles of mobilization. In a linear regression model, an increased percentage of marrow involvement and prior radiotherapy (RT) were statistically significantly associated with a low CD34+ cell collection yield (P = 0.003, and 0.01, respectively). A mobilization regimen of CE plus G-CSF was associated with a significantly higher yield of CD34+ cells as compared to patients receiving G-CSF alone (P = 0.02). CY with G or GM-CSF was not significantly different than G-CSF alone (P = 0.49). Twenty-two of 24 (92%) patients receiving CE with G-CSF achieved a target level of 5 x 10(6) CD34+ cells/kg or more as compared to 11 of 19 (58%) patients receiving G-CSF alone (P = 0.01) and six of 14 (43%) patients receiving CY with G or GM-CSF (P = 0.001). These data suggest that percentage of marrow involvement, prior radiotherapy, and number of prior chemotherapy regimens are important predictors of PBSC yield in patients with MM. These data also suggest that CE plus G-CSF is superior to G-CSF alone or CY plus G/GM-CSF based on mean daily CD34+ cell collection yield. Higher doses of G-CSF (16-32 micrograms/kg/day) can result in adequate CD34+ cell collections in some secondary attempts in patients with MM failing an initial mobilization regimen.
 ...
PMID:Factors influencing collection of peripheral blood stem cells in patients with multiple myeloma. 880 97

15 multiple myeloma patients with severe granulocytopenia after chemotherapy were treated with recombinant human granulocyte colony stimulating factor (Neupogen; Roche). Granulocyte colony stimulating factor (G-CSF) was given s.c. usually in a dose of 5 micrograms/kg for 5-14 (median:8) days. In all cases the increase in ANC was observed; one day after completing therapy the ANC ranged from 2.3 to 19.7 (mean: 10.3) x 10(9)/l. In 3 cases the ANC peak appeared during first (2-4) days of treatment, in one- on 14-th day after 10-day unsuccesful treatment. Generally, ANCs rapidly decreased after discontinuation of treatment to the values observed prior to the last chemotherapy. Both adverse events present in 9 patients and changes in monitored blood biochemistry components were moderate and reversible. In 3 cases symptoms of myeloma progression occurred. The study showed that G-CSF is an efficient and well tolerated drug, but also demonstrated its short-term action.
 ...
PMID:Effect of recombinant human granulocyte colony stimulating factor on granulocytopenia induced by cytotoxic chemotherapy in patients with multiple myeloma. 893 43

In order to shorten the pancytopenic period following high-dose melphalan 140 mg/m2 (HDM) treatment of multiple myeloma patients, we studied the effects of re-infusing granulocyte colony stimulating factor (G-CSF) [Filgrastim, Neupogen]-primed unprocessed whole blood. 30 patients with multiple myeloma were treated with HDM. One litre of blood after 5 or 6 days stimulation with G-CSF (10 micrograms/kg) was drawn, kept unprocessed for 1 day and re-infused 24 h after chemotherapy. Time to granulocyte recovery (> 0.5 x 10(9)/1) and platelet recovery (> 20 x 10(9)/1) were assessed as well as length of hospital stay, number of transfusions and antibiotic use. These 30 patients were compared with 20 historical control patients who were similarly treated but without stem cell support. The response rate was 75% (21/28) including a complete remission (CR) rate of 29% (8/28). Two early deaths due to Aspergillus pneumonia were observed. The median overall survival after HDM has not been reached after a median follow-up of 14 months. 10 patients showed progression at a median of 7 months. Currently, 23 patients are alive with a median follow-up time of 14 months. Haematological recovery was significantly faster in the study group as compared to the historical control group. The neutrophil count reached 0.5 x 10(9)/1 at a median of 14 days after infusion of 1 litre of unprocessed whole blood compared with 38 days in the historical control group. A platelet count of 20 x 10(9)/1 was reached at a median of 26 days compared with 36 days in the historical control group. Length of hospital stay decreased from a median of 43 to 18.5 days. The number of days with antibiotics was reduced from a median of 21 to 6 days. HDM is effective therapy for multiple myeloma. Toxicity of the regimen is considerably reduced by the use of G-CSF-stimulated unprocessed whole blood, an easy to perform and cheap technique to mobilise and collect stem cells.
 ...
PMID:High-dose melphalan with re-infusion of unprocessed, G-CSF-primed whole blood is effective and non-toxic therapy in multiple myeloma. 901 45

The authors assess the activity and toxicity of paclitaxel in previously untreated patients with multiple myeloma. Eighteen patients with previously untreated multiple myeloma were enrolled. Paclitaxel was given in a dose of 250 mg/m2 by a continuous intravenous infusion for 24 hours every 21 days for four cycles. All patients received granulocyte colony stimulating factor in a dose of 5 microg/kg each day until the absolute neutrophil count was 10,000/mm3. All patients were evaluated after four cycles. Four (29%) objective responses were observed in the 14 eligible patients. No complete responses occurred. Three lethal toxicities were observed, two were the result of neutropenic sepsis. Sixty-one percent of patients experienced some type of severe nonhematologic toxicity. Patients who received four cycles of paclitaxel were given further treatment at the discretion of the investigator. The median survival of all eligible patients was 2.8 years, which is comparable with the median survival with melphalan and prednisone of 2.3 years or vincristine, carmustine, melphalan, cylophosphamide, and prednisone of 2.4 years. Paclitaxel in the dosage used in this study has prohibitive toxicity. The four (29%) responses in 14 evaluable untreated patients indicates that paclitaxel is active in the treatment of multiple myeloma. No complete remissions were recorded. Further studies using paclitaxel in a smaller dose, in combination with other agents, or using one of the paclitaxel analogs may be useful in the treatment of multiple myeloma.
 ...
PMID:Paclitaxel as the initial treatment of multiple myeloma: an Eastern Cooperative Oncology Group Study (E1A93). 985 54

Thirty-six patients with multiple myeloma (23 PR1, nine PR2, four stable disease) were entered into a pilot study evaluating the use of CD34+-selected peripheral blood progenitor cell transplantation (PBPCT) following high-dose melphalan alone or high-dose melphalan and total body irradiation. Peripheral blood progenitor cells (PBPCs) were mobilized with cyclophosphamide and granulocyte colony stimulating factor (G-CSF). CD34+ selection using the Cellpro Ceprate-SC system was performed in 22 cases with an adequate yield in 20. 10 patients failed to mobilize sufficient cells to permit selection and in four cases selection was not performed for other reasons. 16 patients therefore received unselected PBPC. Tumour cell contamination was evaluated by IgH gene fingerprinting (fpPCR). Harvested PBPC were fpPCR positive in 13/20 CD34+-selected cases and remained positive after selection in seven. Harvested PBPC were studied in 9/16 patients receiving unselected cells; fpPCR was positive in five and negative in four. There was no difference in event-free survival (EFS) between the CD34+-selected group and the unselected group (median 21 and 26 months, respectively, P=ns). The CD34+-selection process therefore reduced contamination but did not eliminate it completely, and in this small non-randomized study there was no apparent clinical benefit of CD34+ selection.
 ...
PMID:CD34+-selected peripheral blood progenitor cell transplantation in patients with multiple myeloma: tumour cell contamination and outcome. 1002 30

Cyclophosphamide with granulocyte colony stimulating factor (G-CSF) is commonly used to mobilize stem cells in multiple myeloma. Timing of collection is variable and incidence and severity of side effects is substantial. To optimize timing of collection, to reduce side effects and to limit costs of the procedure, we evaluated vinorelbine, a drug shown to have activity in multiple myeloma, in combination with G-CSF as mobilizing regimen. A total of 19 consecutive patients with advanced stage multiple myeloma received one dose of vinorelbine 35 mg/m(2) intravenously on day 1 in an outpatient setting and G-CSF 10 microg/kg/day from day 4 divided in two daily doses. Median CD34+ cell blood counts measured on day 8 of mobilization were 142 x 10(6)/l (range 57-467). One 15-l apheresis on day 8 resulted in sufficient stem cells (median 11.1 x 10(6) CD34+ cells/kg, range 6.2-36.0 prior and median 7.5 x 10(6) CD34+ cells/kg, range 4.0-20.2 post-positive CD34+ cell selection) for transplantation. Hematopoietic recovery was swift with ANC >0.5 x 10(9)/l on day 11 median (range 10-15) and platelets >20 x 10(9)/l on day 12 median (range 10-15) after reinfusion of the stem cells on day 0. No episodes of febrile neutropenia were observed during mobilization. In our institutions cost reduction for the procedure was about 1700 euros compared to the mobilization with cyclophosphamide and G-CSF. Vinorelbine and G-CSF allow precise timing and harvesting of sufficient stem cells, and might be an alternative to cyclophosphamide in the mobilization of stem cells for autologous transplantation in multiple myeloma.
 ...
PMID:Mobilization of peripheral blood progenitor cells with vinorelbine and granulocyte colony-stimulating factor in multiple myeloma patients is reliable and cost effective. 1262 90

Both single and tandem cycles of high dose therapy and autologous peripheral blood stem cell transplantation (ASCT) have been shown to improve survival in multiple myeloma (MM) patients. We report outcomes in 104 MM patients undergoing a single transplant after conditioning with a conventional myeloablative regimen, busulphan and cyclophosphamide. The patients were either in a first (71%), or subsequent remission (29%). Peripheral blood stem cells were mobilized using cyclophosphamide and granulocyte colony stimulating factor. The conditioning regimen consisted of busulphan 0.85 mg/kg given orally every 6 h (16 doses) and cyclophosphamide 60 mg/kg/d given intravenously for 2 d. The entire conditioning, transplant and post-transplant course were in the outpatient setting for 45% patients. At a median follow-up of 26 months (range 2-98 months), the median overall and progression-free survival were 57 months [95% confidence interval (CI) 47-68] and 26 months (95% CI 20-32) respectively. Younger age and higher CD34+ cell dose infused were independently predictive of improved overall and progression-free survival. Busulphan and cyclophosphamide is an effective and well-tolerated preparative regimen for ASCT that can be given to MM patients in the outpatient setting.
 ...
PMID:Favourable results with a single autologous stem cell transplant following conditioning with busulphan and cyclophosphamide in patients with multiple myeloma. 1500 65


1 2 Next >>