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 order to improve prediction of hematopoietic recovery, we conducted a pilot study, analyzing the significance of growth factor receptor expression in autografts as well as endogenous growth factor levels in blood before, during and after stem cell transplantation. Three early acting (stem cell factor (SCF), Flt3 ligand (Flt3) and fetal antigen 1 (FA1)) and three lineage-specific growth factors (EPO, G-CSF and thrombopoietin (Tpo)) were analyzed by ELISA in 16 patients with multiple myeloma (MM) and 16 patients with non-Hodgkin's lymphoma (NHL). The relative number of SCF, Flt3, Tpo and G-CSF receptor positive, CD34+ progenitor cells were measured by flow cytometry in the leukapheresis product used for transplantation in a subgroup of 15 patients (NHL, n = 8, MM, n = 7). Three factors were identified as having a significant impact on platelet recovery. First, the level of Tpo in blood at the time of the nadir (day +7). Second, the percentage of re-infused thrombopoietin receptor positive progenitors and finally, the percentage of Flt3 receptor positive progenitors. On the other hand, none of the analyzed factors significantly predicted myeloid or erythroid recovery. These findings need to be confirmed in prospectively designed studies.
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PMID:Flow cytometric detection of growth factor receptors in autografts and analysis of growth factor concentrations in autologous stem cell transplantation: possible significance for platelet recovery. 1101 42

In order to determine the clinical impact of CD34+ cell selected autologous transplantation in multiple myeloma (MM), we have performed a retrospective case-controlled analysis comparing 21 MM patients receiving high-dose melphalan and autologous transplantation with CD34+ peripheral blood stem cells (PBSC) as front-line therapy to 21 control patients receiving unselected products. Case matching was performed using the following criteria: age and beta2-microglobulin at diagnosis and disease status at the time of transplantation. Both cohorts were homogeneous in term of induction treatment and conditioning regimen. Patients were collected for CD34+ selection after priming with G-CSF alone. Significantly fewer CD34+ cells/kg were infused to patients in the selected group as compared to patients in the control group: 2.2 (range 0.5-14.3) vs 9.4 (range 1.1-15) (P < 0.001). The median time to neutrophil recovery > or =0.05 x 10(9)/l was 10 days for the CD34+ group and 9.5 days for the control group (P = 0.357). The median time to platelet recovery > or = 20 x 10(9)/l was 9 days for the CD34+ group and 4.5 days for the control group (P = 0.005). Response rates were comparable in both groups (85.7% in the CD34+ group vs 90.4% in the control group). At 3 years, event-free survival (32% in the CD34+ group vs 39% in the control group) and overall survival (85% in the CD34+ group vs 79% in the control group) were not significantly different. Finally, use of unselected products dramatically reduced the cost of the transplantation procedure. This study shows that CD34+ cell selected autologous transplantation is more expensive than transplantation with unselected products and does not improve the clinical outcome of patients with MM.
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PMID:Lack of benefit of CD34+ cell selected over non-selected peripheral blood stem cell transplantation in multiple myeloma: results of a single center study. 1102 57

In the literature various regimes are described for successful collection of haematopoietic stem cells in patients with multiple myeloma. Most frequently cyclophosphamide is used, 5 g/m2 combined with different doses of haematopoietic growth factors. In our group the yields and tolerance of three stimulating regimes are compared: 1. cyclophosphamide 5 g/m2 and filgrastim (G-CSF) 5 micrograms/kg 2. cyclophosphamide 5 mg/m2 and filgrastim 10 micrograms/kg 3. cyclophosphamide 5 g/m2 and figrastim 5 micrograms/kg along with erythropoitin 50 IU/kg. Cyclophsphamide is administered always on the first day and the haematopoietic growth factors then from the third day till the end of collection of haematopoitic cells. In patients with multiple myeloma where only four cycles of VAD chemotherapy preceded and where radiotherapy of the axial skeleton was not used, optimal collection of haematopoietic stem cells was achieved after administration of cyclohosphamide 5 g/m2 with subsequent administration of 5 micrograms/kg G-CSF. By increasing the dose of G-CSF to 10 micrograms/kg or adding 50 IU/kg erthropoietin did not lead to a significant improvement of the tolerance and yield of this procedure.
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PMID:[Haematopoietic stem cell mobilization in patients with multiple myeloma--comparison of 3 variations of the stimulating regime]. 1104 5

We have evaluated the outcome of allogeneic haemopoietic stem cell transplantation for multiple myeloma using a conditioning regimen comprising fractionated total body irradiation and high-dose melphalan (110 mg/m2). The study comprised 25 patients (median age 49 years) who had been transplanted by either bone marrow (n = 13) or G-CSF mobilized peripheral blood stem cells (n = 12). Overall transplant-related mortality was 30% but was lower for patients < 50 years of age at transplant (21%). The main cause of treatment-related mortality was viral infection. Of the 19 patients evaluable post-transplant, 17 have so far achieved complete remissions. Currently, with a median follow-up of 3.4 years, 18 out of 25 patients are alive, of whom 15 are in continuing complete remission (CR) and 2 in second remission after suffering localized relapses, which were treated with radiotherapy and donor leucocyte infusions. Patients transplanted after 1 line of previous therapy, < 50 years of age and receiving peripheral blood stem cells (PBSC) rather than bone marrow (BM) had a superior outcome, although there was no statistically significant factor. We conclude that allogeneic transplantation should be considered as a potentially curative option for younger patients with myeloma and that the regimen using fractionated total body irradiation and melphalan has a high CR rate and a relatively low risk of treatment-related mortality, particularly in younger patients.
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PMID:Allogeneic haemopoietic stem cell transplantation for multiple myeloma or plasma cell leukaemia using fractionated total body radiation and high-dose melphalan conditioning. 1114 42

In this study we compared the lymphocyte reconstitution in 13 multiple myeloma (MM), nine acute myeloid leukemia (AML) and 10 chronic myeloid leukemia (CML) patients after allogeneic G-CSF-mobilized PBSC transplantation from HLA-identical siblings. Conditioning regimens included standard total body irradiation + cyclophosphamide (CY), or busulphan + CY, whereas VP-16 was added in patients with advanced disease. Overall comparable numbers of mononuclear cells, CD34+ cells and CD3+ T cells were infused in each group. A significantly higher CD3+ T cell number was observed in MM and AML than in CML patients 1 month after transplant. However, MM patients showed a faster and better recovery of CD4+ T cells than both AML and CML patients at 3 months (P = 0.01 and P = 0.01, respectively) and 12 months (P = 0.01 vs AML, while P = NS vs CML) after transplant, and had a CD4:CD8 ratio > 1 with a median CD4+ T cell value > 400/microl 1 year after transplant. Development of acute graft-versus-host disease (GVHD) did not affect CD4:CD8 ratios but patients who experienced acute GVHD > grade I had lower CD4+ and CD8+ T cell numbers at all time points. However, after excluding patients with GVHD > grade I, MM patients still showed a significantly higher CD4+ T cell value than patients with myeloproliferative diseases 1 year after transplant. These findings suggest that although allogeneic PBSC transplantation induces rapid immune reconstitution, different kinetics may occur among patients with hematological malignancies. In particular, the rapid reconstitution of CD4+ T cells in MM patients may contribute to the low transplant-related mortality achieved in this disease.
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PMID:Different immune reconstitution in multiple myeloma, chronic myeloid leukemia and acute myeloid leukemia patients after allogeneic transplantation of peripheral blood stem cells. 1122 73

We report a case of a patient with IgA kappa multiple myeloma (MM) mobilized with etoposide and subsequently receiving high-dose melphalan (HDM) with stem cell support. She relapsed rapidly post transplantation. Southern blot and fluorescent in situ hybridization analysis showed MLL gene rearrangement in the myeloma cells, which was not detected in the sample at diagnosis or in the PBSC harvested with etoposide plus G-CSF. These observations suggest that clonal rearrangement of the MLL gene is caused by etoposide. Patients with MM undergoing HDM with stem cell rescue may be at an increased risk of not only secondary leukemia, but also secondary genetic abnormalities in myeloma cells, especially those receiving priming with etoposide for peripheral blood stem cell collection.
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PMID:Aggressive neoplastic plasma cell growth with MLL gene rearrangement after high-dose therapy with autologous stem cell support for multiple myeloma. 1131 93

Arsenic trioxide can inhibit proliferation and induce apoptosis in multiple myeloma (MM) cells in vitro and in vivo. In addition to affecting tumor growth, arsenic trioxide has been shown to inhibit angiogenesis, suggesting that it may have significant potency in the treatment of MM. Based on these observations, the clinical efficacy of arsenic trioxide was evaluated in patients with advanced refractory MM using a fixed-dose intravenous infusion given daily for a maximum of 60 days. Nine patients were evaluable. All nine had extensive prior therapy; seven had two or more high-dose chemotherapy cycles with autologous stem cell support. All nine patients had cytogenetic abnormalities, and six had chromosome 13 deletions. Of the four patients who completed more than 30 days of arsenic trioxide infusion, two had >50% reduction in myeloma paraprotein, one had stable disease, and one progressed. Of the five patients with <30 days infusion, two had stable disease and three progressed. Thus, on an intent-to-treat basis, two of nine (23%) patients responded (>50% paraprotein reduction). The regimen was well tolerated except for development of cytopenia, which responded to G-CSF, and a grade III pulmonary complication in one patient. In summary, arsenic trioxide has activity in end-stage, high-risk myeloma and deserves further evaluation in earlier-stage disease.
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PMID:Arsenic trioxide: an emerging therapy for multiple myeloma. 1133 36

A Multiple Myeloma (MM), IgG-lambda stage III-A was diagnosed in a 41-year-old-man. After VAD cycles IgG decreased from 7.5 to 2.4 g/dL. were mobilized with cyclophosphamide and 10 micrograms/Kg G-CSF. Three days after the collection of peripheral stem cell, the patient had fever, nausea, vomiting, liquid stools, shoulder and knee arthralgia and dehydration. Upper GI endoscopy showed esophageal candidiasis and ulcerative necrotic lesions both in stomach and duodenum; the biopsy confirmed necrosis. Simultaneously, the appearance of purpura with maculopapular lesions of diverse sizes appeared in the feet progressing to the limbs and trunk. Hematuria and proteinuria were also observed. Skin biopsy showed leukocytoclastic vasculitis. Renal biopsy showed focal and segmental glomerulonephritis. Serum ANCA, cryoglobulins, anti-HCV and RF were negative, and serum monoclonal IgG was 1290 mg/dL. Daily treatment with i.v. methylprednisolone pulses for 3 days improved skin lesions and digestive involvement. Macroscopic hematuria and proteinuria improved after two months of steroid treatment.
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PMID:[Severe Henoch-Schonlein purpura in a patient with multiple myeloma]. 1134 14

In 90 consecutive patients with multiple myeloma, we investigated the feasibility of administering a tandem high-dose therapy regimen, using whole blood for rescue after the first and leucapheresis harvested between the two high doses, for rescue after the second high dose. After 5 days of G-CSF 1 litre of whole blood (WB) was obtained, left undisturbed at 4 degrees C and reinfused 24 h after HDM (140 mg/m(2)). Patients not in progression after 3-6 months were again mobilised, leucapheresed and treated with busulphan 16 mg/kg and cyclophosphamide 120 mg/kg (Bu/Cy) and reinfusion. In 90 patients, WB contained a mean (range) of 0.57 (0.02-3.22) x 10(6)/kg CD34(+) cells. Recovery after HDM was in 13 days for granulocytes and in 18 days for platelets, with 11 patients not recovering within 3 months. There were three toxic deaths. Sixty-six patients qualified for harvesting after HDM. In the first 11, marrow was harvested. The subsequent 55 patients were mobilised and in 45 the preset minimum of 1.5 x 10(6) CD34(+) cells was obtained. Forty-nine patients actually received Bu/Cy. Recovery after Bu/Cy and marrow reinfusion was in 35 days for granulocytes and 20 days for platelets, with two of five patients not recovering after 3 months. After Bu/Cy and leucapheresis reinfusion, recovery was in 17 days for granulocytes and in 34 days for platelets. Nine patients did not recover within 3 months. There were four toxic deaths. The median overall survival from diagnosis for patients receiving HDM was 49 months and for patients also receiving Bu/Cy, 84 months. We conclude that WB rescue after HDM followed by leucapheresis and a second transplant is feasible in the majority of patients. Better mobilisation techniques are required to increase the number of patients who can receive the second transplant.
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PMID:High-dose melphalan with G-CSF-stimulated whole blood rescue followed by stem cell harvesting and busulphan/cyclophosphamide with autologous stem cell transplantation in multiple myeloma. 1143 2

In general, the mobilization of peripheral blood progenitor cells (PBPC) in multiple myeloma (MM) patients is poor and is achieved in most cases by combined cyclophosphamide and G-CSF. This study was performed to examine the efficacy of combined ifosfamide/epirubicine and G-CSF for PBPC mobilization and purging. Sixteen patients suffering from multiple myeloma in stage II/A and III/A according to Durie and Salmon underwent chemotherapy consisting of a total of three cycles of ifosfamide (3 g/m(2) on days 1 and 2 and epirubicine 80 mg/m(2) on day 1) and G-CSF (10 or 20 microg/kg body weight (BW) daily until harvesting). PBPC harvesting was performed after the first and third cycle of chemotherapy. The median number of PBPC after the first cycle of chemotherapy was 7.79 x 10(6) CD34+ cells/kg BW (ranging from 0.94-26.36 x 10(6)) and 6.38 x 10(6) CD34+ cells/kg BW (ranging from 0.79-29.31 x 10(6)) after the third cycle of chemotherapy. Clinical re-evaluation after three cycles of chemotherapy showed 13 (81 per cent) patients in partial remission (PR), two (12 per cent) in complete remission (CR) and one (6.25 per cent) in stable disease (SD). No major side-effects were observed, six patients developed hematological toxicity stage IV WHO for a median of 3.9 days but no serious infection episodes occurred. Combined ifosfamide/epirubicin and standard G-CSF is able to mobilize sufficient PBPC without serious side-effects for patients with MM and for purging procedures resulting in a high proportion of complete remissions after tandem high-dose melphalan chemotherapy.
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PMID:Ifosamide, epirubicin and granulocyte colony-stimulating factor: a regimen for successful mobilization of peripheral blood progenitor cells in patients with multiple myeloma. 1143 75


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