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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Data from autologous peripheral blood progenitor cell (PBPC) transplant recipients were used for cost analysis and modelling so as to link the main intervention procedures and clinical events to resource use and costs. This cohort consisted of 64 patients from 4 to 62 years old at transplantation (mean, 36.9 years) who underwent a first transplant between August 1994 and May 1997. The main indications for transplantation were non-Hodgkin's lymphomas (47%), multiple myeloma (30%) and Hodgkin's lymphomas (15%). The course of a patient during the whole transplant procedure was modelled using a Markov chain of six states of health: (1) mobilisation and recovery of PBPC; (2) post-mobilisation phase; (3) conditioning and transplant; (4) critical haematological reconstitution; (5) non-critical haematological reconstitution; (6) death. The probability of transition between the different health states, together with the estimated costs, were the input for the Markov model. The model also managed transition probabilities depending both on the current health state and on various demographic, clinical and procedure-related covariates unique to the patient. The expected time spent in each clinical state and the expected total cost were, therefore, estimated. This analysis gave an actual total cost per transplanted patient of $26,600 (95% range: $24,700 to $43,500) while mean duration was 197 days. The expenses for in-hospital stay accounted for 80% of the costs. Both the probability of staying in the different states, and the consequent cost were dependent on the number of CD34-positive cells collected, the phase and the type of the disease, the subset of patients (either children or adults), and the post-transplant G-CSF prophylaxis. The sensitivity of the estimates to alternative assumptions was studied, and the method of comparing alternative future scenarios by the model was explored.
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PMID:A model for analysing the cost of autologous peripheral blood progenitor cell (PBPC) transplantation. 1021 50

Recent studies concerning the numbers of circulating clonal B cells in patients with multiple myeloma (MM) have reported conflicting data regarding the exact levels of clonal B cells and the existence of clonal cells in the CD34 compartment. In this report we show that high numbers of clonal cells with a phenotype of late-stage B cells or pre-plasma cells were present in the peripheral blood (PB) of a patient with MM. During treatment the initial high level of PB clonal cells was markedly reduced and remained low (<1%) post transplant, even after disease progression. In addition, we found that the MM clone did not include a B-progenitor population defined by CD34.
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PMID:High numbers of clonal CD19+ cells in the peripheral blood of a patient with multiple myeloma. 1023 90

Multiple myeloma with IgG-lambda monoclonal gammopathy and severe renal impairment with light-chain deposit disease was diagnosed in a 51-year-old man. Following conventional therapy with VAD (vincristine, adriamycin, dexamethasone) a partial remission was achieved. Peripheral blood stem cells (PBSC) were then collected following mobilization with cyclophosphamide and recombinant human granulocyte colony-stimulating factor and enriched for CD34-positive cells by immunoaffinity column. Fourteen months after diagnosis high-dose melphalan was given, followed by infusion of CD34-positive PBSC. Aside from mild oral mucositis and trigonitis, high-dose therapy was tolerated well. After he underwent PBSC transplantation his renal function improved, and the patient has been in in continuous complete remission for 1 year. Thus, high-dose chemotherapy can be safely administered to patients with multiple myeloma and severe renal impairment. Our findings confirm previous reports summarized in the current presentation.
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PMID:Effect of high-dose melphalan and peripheral blood stem cell transplantation on renal function in patients with multiple myeloma and renal insufficiency: a case report and review of the literature. 1034 51

As in other malignancies, peripheral blood progenitor cells (PBPC) have almost completely replaced bone marrow as the source of stem cells for autologous transplantation in multiple myeloma. PBPC collection could be optimized either by reducing contamination by the malignant clone or by increasing hematopoietic quality of the graft. Currently, the most promising technique for purifying the harvest is CD34 cell selection. Several pilot studies have shown the feasibility of this method in MM. However controlled studies are necessary to assess the clinical impact of CD34+ cell selection. In the IFM 94 study, CD34+ selection was optional. There was no significant difference between 50 patients receiving a CD34+ selected graft and 133 patients receiving non-selected PBPC, as regards duration of neutropenia, duration of thrombocytopenia, response rate, EFS or survival. Hematopoietic recovery after transplantation is related to the number of CD34+ cells infused. The optimal regimen for mobilizing the requested CD34+ yield is not yet known. We have completed a randomized study comparing the combination of SCF plus G-CSF and G-CSF alone after priming with cyclophosphamide 4 g/m2. The median number of leukaphereses to reach the target yield of 5x10(6) CD34+ cells/kg was 1 in the SCF group (N=55) versus 2 in the G-CSF group (N=47) (p=0.008). The median number of CD34+ cells collected in the first leukapheresis was 11. 6x10(6) in the SCF group versus 4x10(6) in the G-CSF group (p=0.003). These results are in line with those observed in other trials testing the combination of SCF and G-CSF to improve PBPC collection.
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PMID:Optimizing peripheral blood progenitor cell autologous transplantation in multiple myeloma. 1036

For autologous stem cell transplantation, it is common practice to infuse at least 2 x 10(6)/kg CD34+ cells to ensure rapid engraftment. However it was recently claimed that increasing the threshold to 5 x 10(6)/kg leads to a faster platelet engraftment. To evaluate these threshold values in our patient population we undertook a retrospective analysis of 127 autologous transplants performed at our institution between 1992 and 1998. Diagnoses included Hodgkin's and non-Hodgkin's lymphoma, myeloma, acute leukaemias and solid tumours. The transplant was peripheral blood stem cells in 107 cases and CD34-selected peripheral blood stem cells in 20 cases. The median number of transplanted CD34+ cells was 3.2 x 10(6)/kg (range 0.64-25.9 x 10(6)/kg). Haematopoietic recovery to a neutrophil count >0.5 x 10(9)/l took a median of 10 (range 5-16) days from transplant. When comparing patients receiving at least 5 x 10(6)/kg and 2-5 x 10(6)/kg CD34+ cells we found a significant reduction in the median number of days with fever (1 vs 3.5 days, P = 0.0025), incidence of fever (78.8 vs 92.1%, P = 0.032) as well as duration of antibiotic treatment (7 vs 10 days, P = 0.038). This was paralleled by a faster neutrophil recovery to 0.5 x 10(9)/l (9 vs 10 days, P = 0.047). There was no significant difference in the number of platelet or red cell transfusions between the two groups. We conclude that transplantation with a stem cell dose of at least 5 x 10(6)/kg CD34+ cells reduces infectious complications and should thereby increase the safety of this type of therapy while reducing duration (and cost) of antibiotic therapy. The transplantation threshold should thus not remain at 2 x 10(6)/kg particularly in patients with a good stem cell mobilisation capacity.
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PMID:Using at least 5x10(6)/kg CD34+ cells for autologous stem cell transplantation significantly reduces febrile complications and use of antibiotics after transplantation. 1038 58

The kinetics of mobilization and optimal timing of peripheral blood progenitor cell (PBPC) collection were evaluated in 190 patients with multiple myeloma undergoing stem cell harvest after mobilization with cyclophosphamide, prednisone and G-CSF. There was a strong correlation between the WBC count and the number of CD34+ cells circulating in peripheral blood (r = 0.875). Initiating leukapheresis based on rising WBC and platelet counts rather than on a fixed day increased the mean number of CD34+ cells 115% (9.7 to 20.9 x 10(6) CD34+ cells/kg; P = 0.010) for the total of all leukaphereses and 59% for the total of all CD34-selected products (5.1 to 8.1 x 10(6) CD34+ cells/kg; P = 0.011). Although the yield and purity of the CD34-selected product were not significantly affected (P > or = 0.071), the percentage of patients with concentrations of CD34+ cells in the initial leukapheresis of > 1% increased from 47% to 70% (P = 0.004). The mean purity of the selected product was related to the starting percentage: 48.9% if < 1% and 81.5% if > or = 1% (P < 0.001). Collection of stem cells based on rising WBC and platelet counts significantly increased the number of CD34+ cells in leukaphereses and CD34-selected products in comparison with collection on a fixed day.
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PMID:Collection of peripheral blood progenitor cells (PBPC) based on a rising WBC and platelet count significantly increases the number of CD34+ cells. 1043 30

Stem cell factor (SCF) has been shown to synergize with filgrastim to mobilize CD34(+) cells into the peripheral blood. To determine if addition of SCF to chemotherapy and filgrastim reduces the number of leukaphereses required to achieve a target yield of 5 x 10(6) CD34(+) cells/kg, 102 patients with multiple myeloma were randomized to receive mobilization chemotherapy with cyclophosphamide (4 g/m(2)) and either SCF (20 micrograms/kg/d) combined with filgrastim (5 micrograms/kg/d) or filgrastim alone (5 micrograms/kg/d), administered daily until leukaphereses were completed. After collection, patients were treated with myeloablative therapy supported by autologous peripheral blood progenitor cell (PBPC) infusion and filgrastim (5 micrograms/kg/d). There was a significant difference between the treatment groups in the number of leukaphereses required to collect 5 x 10(6) CD34(+) cells/kg (median of 1 v 2 for SCF + filgrastim and filgrastim alone, respectively, P =.008). Patients receiving the combination of SCF plus filgrastim had a 3-fold greater chance of reaching 5 x 10(6) CD34(+) cells/kg in a single leukapheresis compared with patients mobilized with filgrastim alone. The median CD34(+) cell yield was significantly increased for the SCF group in the first leukapheresis (11.3 v 4.0 x 10(6)/kg, P =.003) and all leukaphereses (12.4 v 8.2 x 10(6)/kg, P =.007). Total colony-forming unit-granulocyte-macrophage (CFU-GM) and mononuclear cell counts were also significantly higher in the SCF group in the first leukapheresis and in all leukaphereses. As expected for patients mobilized to an optimal CD34(+) cell yield, the time to engraftment was similar between the 2 treatment groups. Cells mobilized with the combination of SCF plus filgrastim were thus considered effective and safe for achieving rapid engraftment. Treatment with SCF plus filgrastim was well tolerated, with mild to moderate injection site reactions being the most frequently reported adverse events. There were no serious allergic-like reactions to SCF. The addition of SCF to filgrastim after cyclophosphamide for PBPC mobilization resulted in a significant increase in CD34(+) cell yield and a concomitant reduction in the number of leukaphereses required to collect an optimal harvest of 5 x 10(6) CD34(+) cells/kg.
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PMID:Stem cell factor in combination with filgrastim after chemotherapy improves peripheral blood progenitor cell yield and reduces apheresis requirements in multiple myeloma patients: a randomized, controlled trial. 1043 9

A large group of patients relapsing after allogeneic bone marrow transplantation (BMT) have obtained remission after infusion of leukocytes from their original donor, suggesting a graft-versus-myeloma effect. However, side effects such as graft-versus-host disease and myelosuppression are severe, and sometimes fatal, complications of this therapeutic approach. Previously we demonstrated that patients with leukemia who lack donor hematopoiesis in relapse after BMT experience severe and lasting aplasia after infusion of donor leukocytes. In two patients - one with extramedullary and one with marrow relapse after a sex-mismatched transplantation - we analyzed hematopoietic chimerism by cell sorting and bone marrow cultures. CD34-positive cells, CD4-CD8-positive cells, committed progenitors, and LTC-IC were of donor origin, as demonstrated by two-color fluorescence in situ hybridization (FISH). Additionally, in relapse complete donor T-cell chimerism was seen. In contrast, plasma cells were of recipient origin in the patient who had a relapse in the bone marrow. Both patients were treated with infusions of donor leukocytes from their original donor. Neither patient suffered myelosuppression, and one achieved a stable complete remission.
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PMID:Hematopoietic donor chimerism and graft-versus-myeloma effect in relapse of multiple myeloma after allogeneic bone marrow transplantation. 1046 Mar 52

The ribosome-inactivating protein, Shiga-like toxin-1 (SLT-1), targets cells that express the glycolipid globotriaosylceramide (CD77) on their surface. CD77 and/or SLT-1 binding was detected by flow cytometry and immunocytochemistry on lymphoma and breast cancer cells recovered from biopsies of primary human cancers as well as on B cells or plasma cells present in blood/bone marrow samples of multiple myeloma patients. Breast cancer cell lines also expressed receptors for the toxin and were sensitive to SLT-1. Treatment of primary B lymphoma, B-cell chronic lymphocytic leukemia, and myeloma B or plasma cells with SLT-1-depleted malignant B cells by 3- to 28-fold, as measured by flow cytometry. Depletion of myeloma plasma cells was confirmed using a cellular limiting dilution assay followed by reverse transcriptase-polymerase chain reaction analysis of clonotypic IgH transcripts, which showed a greater than 3 log reduction in clonotypic myeloma cells after SLT-1 treatment. Receptors for the toxin were not detected on human CD34(+) hematopoietic progenitor cells (HPC). HPC were pretreated with a concentration of SLT-1 known to purge primary malignant B cells and cultured for 6 days. The number of HPC was comparable in toxin-treated and untreated cultures. HPC were functionally intact as well. Colony-forming units (CFU) were present at an identical frequency in untreated and SLT-1 pretreated cultures, confirming that CFU escape SLT-1 toxicity. The results suggest the ex vivo use of SLT-1 in purging SLT-1 receptor-expressing malignant cells from autologous stem cell grafts of breast cancer, lymphoma, and myeloma patients.
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PMID:Shiga-like toxin-1 receptor on human breast cancer, lymphoma, and myeloma and absence from CD34(+) hematopoietic stem cells: implications for ex vivo tumor purging and autologous stem cell transplantation. 1051 95

High-dose melphalan (200 mg/m2) followed by one or more autologous peripheral blood stem cell transplantations is a safe and effective treatment regimen for multiple myeloma. This treatment regimen is as effective as standard therapy for myeloma in older (>65 years) patients and in patients with renal failure. However, advanced age (>50 years), duration of prior standard therapy (> 12 months), and a low CD34 mobilization potential (<20 x 10(6)/kg) are associated with a higher incidence of cytogenetic myelodysplasia. Future efforts directed at curing multiple myeloma should incorporate the best remission induction regimens presently available and should use consolidation/maintenance treatment (eg, idiotype/dendritic cell vaccination and dexamethasone/cyclophosphamide/etoposide/cisplatin combination chemotherapy) to enhance sustained complete remission. Other options to improve the treatment of myeloma include novel adjunctive therapies that target the myeloma cell microenvironment (eg, bisphosphonates, thalidomide, other antiangiogenesis agents) and allogeneic transplantation techniques to induce a graft-versus-myeloma effect.
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PMID:Novel approaches in myeloma therapy. 1052 92


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