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)

Recombinant human hematopoietic growth factors are widely used in the treatment of multiple myeloma (MM) especially due to the increasing role of autologous blood stem cell transplantation (ABSCT). We report a patient with MM in whom rapid extramedullary progression of disease was observed during stem cell mobilization with G-CSF. In 56-year-old man with relapsing IgG lambda MM myeloablative therapy with ABSCT was planned 2 years after diagnosis. G-CSF is increasing doses was used for mobilization. Ten days after the start of G-CSF therapy 2 extramedullary (subcutaneous) myeloma infiltrates appeared. For the second mobilization high dose cyclophosphamide and VP-16 with subsequent G-CSF was used. During the time of chemotherapy tumour infiltrates disappeared, however, after one week of G-CSF treatment rapid progression of disease with the formation of multiple extramedullary infiltrates occurred and the patient died in June 1996. Small pieces of subcutaneous tumour infiltrates were removed at autopsy and immediately frozen in liquid nitrogen. Using the panel of specific antibodies the expression of cytokine receptors (IL-1, 2, 3, 6, 7, 8, 10, SCF, gp130, G-CSF, GM-CSF, EPO) and Fas, Pgp and 24-34 kD multidrug resistance-associated protein were examined. However, no expression of cytokine receptors on tumor cells was found. On the contrary, high positivity of surface MDR associated proteins was observed.
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PMID:[Progression of multiple myeloma during treatment with recombinant G-CSF and absence of G-CSF and IL-6 cell surface receptors on malignant cells]. 992 31

We performed a phase II study to test the efficacy and feasibility of induction therapy with vincristine, adriamycin and dexamethasone (VAD) and intermediate-dose melphalan, 70 mg/m2 (IDM), to autologous or allogeneic stem cell transplantation in newly diagnosed multiple myeloma (MM). A total of 77 patients received two cycles of VAD (n = 62) and/or two cycles of i.v. IDM 70 mg/m2 (n = 15) combined with G-CSF. PBSC were harvested after the first IDM, successfully in 87% of patients. Patients with a response to induction received myeloablative therapy with PBSCT (n = 50) followed by IFN maintenance or allo-BMT (n = 11). Seventy-two per cent of patients achieved a response after VAD which increased to 85% after IDM. Of patients who received PBSCT and allo-BMT, 24% and 45% achieved CR, respectively. Toxicity of induction consisted mainly of bone marrow suppression after IDM (median 8 days) with prolonged aplasia in 11% of patients after the second IDM. Only six infections WHO grade 3 occurred during induction. Treatment-related mortality of PBSCT and allo-BMT was 6% and 18%, respectively. Median time of follow-up is 44 months, and 50% of patients after PBSCT and 60% of patients after allo-BMT are still in remission. Survival rates of all patients were 82%, 75% and 63%, and for transplanted patients 86%, 79% and 68% after 12, 24 and 36 months. Well known prognostic factors, including alpha-IFN maintenance after PBSCT, were not significant for response or survival although patients in CR after allo-BMT had a strong tendency for better outcome. VAD/IDM is an effective and safe induction therapy for autologous and allogeneic stem cell transplantation. Based on these observations a phase III trial was started in October 1995 comparing IFN maintenance with PBSCT and allo-BMT after response to induction with VAD and IDM.
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PMID:Induction therapy with vincristine, adriamycin, dexamethasone (VAD) and intermediate-dose melphalan (IDM) followed by autologous or allogeneic stem cell transplantation in newly diagnosed multiple myeloma. 1010 May 74

The study purpose was to determine if G-CSF plus dose-intensive cyclophosphamide 5.25 g/m2, etoposide 1.05 g/m2 and cisplatin 105 mg/m2 (DICEP) results in superior autologous blood stem cell mobilization (BSCM) than less intensive chemotherapy. From January 1993 until May 1997, 152 consecutive patients with non-Hodgkin's lymphoma (n = 55), breast cancer (n = 47), Hodgkin's disease (n = 14), multiple myeloma (n = 9), AML (n = 9), or other cancers (n = 18) initially underwent BSCM by one of three methods: Group 1: G-CSF alone x 4 days (n = 30). Group 2: disease-oriented chemotherapy, dosed to avoid blood transfusions, followed by G-CSF starting day 7 or 8, and apheresis day 13 or 14 (n = 82). Group 3: DICEP days 1-3, G-CSF starting day 14, and apheresis planned day 19, 20 or 21 (n = 40). A multivariate analysis was performed to determine which factors independently predicted BSCM. The median peripheral blood CD34+ (PB CD34+) cell count the morning of apheresis linearly correlated with the number of CD34+ cells removed per litre of apheresis that day. The median PB CD34+ cell count and median CD34+ cells x 10(6) removed per litre of apheresis were highest for Group 3, intermediate for Group 2, and lowest for Group 1. By multivariate analysis, mobilization group (3 > 2 > 1), disease other than AML, no prior melphalan or mitomycin-C, and less than two prior chemotherapy regimens predicted better BSCM. Out of 15 Group 3 patients who had infiltrated marrows, 11 had no detectable cancer in marrow and apheresis products after DICEP. These data suggest that DICEP results in superior BSCM than less intensive chemotherapy regimens.
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PMID:Superior autologous blood stem cell mobilization from dose-intensive cyclophosphamide, etoposide, cisplatin plus G-CSF than from less intensive chemotherapy regimens. 1019 94

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

Thirty-two patients with multiple myeloma (MM) were autografted in our Centre over a 3-year period. Twenty-three patients had a newly diagnosed MM submitted to one induction regimen and 9 had a refractory or relapsing disease treated with at least two different chemotherapy lines: 15 out of 32 patients were sensitive to conventional treatment. In 2 patients BM was harvested while in the majority PBSC were collected after administration of 7 g/m2 Cyclophosphamide plus G-CSF (in 25 patients) or G-CSF alone at the dose of 16 microg/Kg/daily for 5-7 days (in 5 patients). Conditioning regimen was busulfan 16 mg/Kg plus melphalan 120 mg/m2. One patient died of cerebral hemorrhage after reinfusion of PBSC. Out of 31 evaluable patients, 24 (77%) had a response which was complete in 6 patients (19%) and partial in 18 patients (58%), 5 cases (17%) had no response, and 2 (6%) showed myeloma progression. There was a statistical difference in the outcome between newly diagnosed and pretreated patients (p = 0.003). At a median follow-up of 9 months (range 5-37), two patients had died for progression and 3 out of the 29 alive, relapsed after 17, 18 and 36 months respectively. Although median overall survival was not reached, there was a significant survival benefit for autografted patients in comparison with a matched control group conventionally treated in our Centre before 1994 (p = 0.02).
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PMID:Autologous stem cell transplantation for multiple myeloma: a single centre experience. 1035 38

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

Autologous peripheral blood stem cell (PBSC) transplantation results in rapid hematologic recovery when sufficient numbers of CD34+ cells/kg are infused. Recent studies suggest that filgrastim (G-CSF) administration following transplantation leads to more rapid neutrophil recovery and lower total transplant costs. This study compares the use of G-CSF (5 microg/kg/day) with sargramostim (GM-CSF) 500 microg/day from day 0 until neutrophil recovery (ANC >1500/mm3) in patients with breast cancer or myeloma who had PBSC mobilized with the combination of cyclophosphamide, etoposide, and G-CSF. Twenty patients (13 breast cancer and seven myeloma) received GM-CSF and 26 patients (14 breast cancer and 12 myeloma) received G-CSF. The patients were comparable for age and stage of disease, and received stem cell grafts that were not significantly different (CD34+ x 10(6)/kg was 12.5 +/- 11.1 (mean +/- s.d.) for GM-CSF and 19.8 +/- 18.5 for G-CSF; P = 0.10). The use of red cells (2.8 vs 2.3 units), and platelet transfusions (2.5 vs 3.1) was similar for the two groups, as was the use of intravenous antibiotics (4.3 vs 4.6 days) and the number of days with temperature >38.3 degrees C (2.3 vs 1.8). Platelet recovery was also similar in both groups (platelets >50,000/mm3 reached after 11.8 vs 14.9 days). The recovery of neutrophils, however, was faster using G-CSF. ANC >500/mm3 and >1000/mm3 were reached in the GM-CSF group at 10.5 +/- 1.5 and 11.0 +/- 1.7 days, respectively, whereas with G-CSF only 8.8 +/- 1.2 and 8.9 +/- 2.2 days were required (P < 0.001). As a result, patients given G-CSF received fewer injections than the GM-CSF patients (10.9 vs 12.3). Resource utilization immediately attributable to the use of growth factors and the duration of pancytopenia, excluding hospitalization, were similar for the two groups. This study suggests that neutrophil recovery occurs more quickly following autologous PBSC transplant using G-CSF in comparison to GM-CSF, but the difference is not extensive enough to result in lower total cost.
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PMID:Hematopoietic growth factor after autologous peripheral blood transplantation: comparison of G-CSF and GM-CSF. 1041 11

An interim report evaluating the feasibility of myeloablative therapy followed by peripheral blood stem cell (PBSC) autotransplant in patients aged >60 years is presented. In the last 2 years 19 patients >60 years old with several oncological conditions, mostly hematological, underwent PBSC autotransplant either as salvage therapy following relapse or resistance to conventional treatment, or as consolidating therapy as a part of a well defined protocol. There were 13 males and six females; the mean age was 66.9 years (range 61-76 years); nine patients had resistant or relapsed lymphoma, six myeloma, two acute leukemia, one Waldenstrom's disease and one lung cancer. Myeloablative schemes included BEAM exclusively for lymphomas, busulfan and melphalan (Bu-MPH) mainly for myeloma, busulfan and cyclophosphamide (Bu-CTX) for lymphomas and leukemia and VP-16 and CTX for lung cancer. Mobilization of CD34+ cells was achieved in all patients with the combination of high-dose CTX and G-CSF with collections between 2.83 to 19.04 x 10(6)/kg (mean 7.1). All patients engrafted with a median time for recovery of PMN (>0.5 x 10(3)/microl) of 10 days (range 8-12 days) and for PLT (>20 x 10(3)/microl) of 12 days (range 10-17 days). Major responses were obtained in 15 of 16 patients evaluable for response and eight patients entered CR; overall eight patients are in CR, five are alive with disease, five are dead from disease progression and one is dead because of congestive heart failure 7 months following PBSC autotransplant. No early deaths following the procedure occurred; major side-effects were grade I-II mucositis (58%), fever with documented sepsis (10%), pneumonia (5%), cardiac, renal and liver toxicity (5%). Cardiac function was evaluated before and after myeloablative therapy by VEF in all patients; no significant modifications were necessary. In conclusion, our experience demonstrates that myeloablative therapies in older selected patients can be feasible; the feasibility of introducing PBSC autotransplantation following myeloablative therapy as a front-line treatment in patients aged >60 years, needs accurate guide lines for selection of appropriate patients.
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PMID:Analysis of feasibility of myeloablative therapy and autologous peripheral stem cell (PBSC) transplantation in the elderly: an interim report. 1041 15

High dose therapy followed by autologous peripheral blood progenitor cell (PBPC) transplantation has recently become an encouraging treatment option for younger patients with multiple myeloma (MM). The influence of the growth factors used for progenitor mobilization on myeloma cells is not known. We report on a patient suffering from IgG kappa myeloma who had been in stable, very good partial remission for seven months after standard therapy until PBPC mobilization with granulocyte-colony stimulating factor (G-CSF, Filgrastim) was initiated. Massive extramedullary disease progression occured coincidentally with the administration of G-CSF. The case suggest the possibility of myeloma stimulation by G-CSF during PBPC mobilization.
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PMID:Massive extramedullary disease progression in a patient with stable multiple myeloma during G-CSF priming for peripheral blood progenitor mobilization. 1042 18

Eighty-eight previously autografted (78 transplanted twice and 10 once) myeloma patients who had no cryopreserved stem cells available for possible future use received G-CSF for mobilization of stem cells. One-fourth of the patients had progressive disease at the time of apheresis. All patients had received 200 mg/m2 melphalan for the first transplant. The interval between the preceding transplant and the harvest was 5-68 months (median 29). A total of 0.46-9.16 (median 3.03) x 10(6) CD34+ cells/kg were collected. More than 2 x 10(6)/kg CD34+ cells were collected in 76% of the patients, and > or = 5 x 10(6)/kg in 14%. On multivariate analysis, patients with platelet counts of > or = 200 x 10(9)/l (P < 0.0001), those who had not received any myelosuppressive chemotherapy between the last transplant and the collection (P = 0.02), and those who had received interferon-alpha for < or = 6 months (P = 0.03) had better collections. Eleven of 12 patients autografted with these cells had prompt neutrophil recovery (median 10 days to 0.5 x 10(9)/l) but recovery to 50 x 10(9)/l platelets was delayed or incomplete in 11 of 12. We conclude that it is possible to harvest peripheral blood stem cells with G-CSF stimulation in patients who have been autografted previously. Limited data suggest that platelet recovery may be suboptimal when these cells are used. These findings have practical implications for patients with malignant diseases in remission after autografting who may be candidates for future salvage therapy but have no stem cells stored, and for patients with chronic myeloid leukemia who are on long-term interferon-alpha therapy to attain cytogenetic remission for eventual collection of normal stem cells.
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PMID:Collection of peripheral blood stem cells after a preceding autograft: unfavorable effect of prior interferon-alpha therapy. 1043 28


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