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)

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

Harvesting of peripheral blood stem cells (PBSCs) following chemotherapy and G-CSF administration is currently performed for hematological therapies. However, a procedure based on the use of a large quantity of G-CSF is relatively costly. Therefore, we retrospectively compared the effects of two PBSC mobilization procedures in a population with recently diagnosed multiple myeloma. The first procedure consisted of chemotherapy and systematic G-CSF administration (group 1: 24 patients). The second consisted of chemotherapy alone, G-CSF having been administered only in the case of failure of PBSC mobilization or delayed white blood cell (WBC) recovery (group 2: 28 patients). Leukapheresis was performed when WBC recovery reached 1 x 10(9)/l if the peripheral blood CD34+ cell count was over 10/microl. Leukapheresis was maintained until a total of 2.5 x 10(6) CD34+ cells/kg was harvested. A significant difference was observed between the two groups only in regard to the median period of WBC recovery (delayed for group 2) and the number of CD34+ cells/kg collected on the first leukapheresis (higher for group 1) but not to the proportion of patients with failure of PBSC collection. Ten group 2 patients, who had insufficient CD34+ cells after WBC recovery or delayed WBC recovery, received G-CSF which resulted in sufficient PBSC harvesting in nine. To obtain a sufficient CD34+ cell level, the patients without systematic G-CSF administration had more leukaphereses (2.1 vs 1.5) but the mean consumption of G-CSF per patient was eight times less than in the other group. Nonsystematic use of G-CSF before WBC recovery or preferentially its introduction just after, could be an interesting economical alternative in PBSC mobilization but should be assessed by a prospective controlled study of cost/efficacy.
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PMID:Blood stem cell collection using chemotherapy with or without systematic G-CSF: experience in 52 patients with multiple myeloma. 1048 28

Recently it was reported that Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) infects bone marrow (BM) dendritic cells (DC) in multiple myeloma (MM) patients and therefore might play a role in MM development. Because of the use of myeloid growth factors like GM-CSF and G-CSF for the mobilization of peripheral blood progenitor cells (PBPC), the subsequent increase of DC precursors might imply a risk for KSHV contamination in PBPC grafts. Therefore, in this study leukapheresis products and ex vivo cultured CD34+ cell suspensions were analysed. KSHV DNA could not be amplified in any of them.
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PMID:Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) DNA sequences are absent in leukapheresis products and ex vivo expanded CD34+ cells from multiple myeloma patients. 1088 29

We retrospectively analyzed factors influencing PBPC mobilization during steady-state hematopoiesis in 52 patients with malignant lymphoma (n=35) or multiple myeloma (n=17) who received 77 cycles of G-CSF (12.5-50 microg G-CSF/kg/day). For 15 of these patients, the first mobilization cycle (12.5 microg G-CSF/kg/day) was followed by a second course with an increased dose of G-CSF (25 or 50 microg/kg/day). Leukapheresis was started on day 4, about 2 h after s.c. G-CSF administration, and repeated on 2-5 consecutive days. CD34+ cells were determined by flow cytometry in each apheresis product and in the peripheral blood prior to G-CSF administration, beginning on day 4. Colony assays were performed on cryopreserved samples prior to autografting. In the 15 patients receiving two mobilization cycles the higher G-CSF dose was associated with higher levels of CD34+ cells, a higher mean yield of CD34+ cells per apheresis (p<0.05), and a higher percentage of successful (>2x10(6) CD34+ cells/kg) collections (p=0.058). Patients with limited previous cytotoxic therapy (n=19, up to six cycles of a standard regimen such as CHOP and/or less than 20% marrow irradiation) who received a daily dose of 12.5 microg G-CSF/kg had higher levels of circulating CD34+ cells, a higher mean yield of CD34+ cells per apheresis (p<0.05), and a higher percentage of successful collections (p<0.05) compared with patients previously treated with more intensive radiochemotherapy (n=15). Ten of 20 patients (50%) who failed during the first cycle were successful during subsequent cycles with escalated doses of G-CSF. Trough levels of circulating CD34+ cells on day 4 were predictive for success or failure to achieve >2x10(6) CD34+ cells/kg, especially in heavily pretreated patients. In conclusion, a daily dose of 12.5 microg G-CSF/kg seems sufficient to mobilize PBPC during steady-state hematopoiesis in the majority of patients who have received limited previous radiochemotherapy. Higher doses of G-CSF, up to 50 microg/kg/day, mobilize more PBPC and should be considered for patients previously treated with intensive radiochemotherapy or those failing to mobilize sufficient numbers of CD34+ cells with lower doses of G-CSF.
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PMID:Factors influencing G-CSF-mediated mobilization of hematopoietic progenitor cells during steady-state hematopoiesis in patients with malignant lymphoma and multiple myeloma. 1055 May 56

Three different methods for determination of CD34+ cells in G-CSF-mobilized peripheral blood were compared. The methods were: the Milan/Mulhouse protocol, the ISHAGE guidelines for CD34+ cells enumeration and our own protocol. The procedure we have adopted is essentially a Milan/Mulhouse protocol-derived methodology combined with a multiparametric approach using the PAINT-A-GATE software analysis program. The samples were collected from 70 patients affected by acute leukemia, non-Hodgkin's lymphoma, Hodgkin's lymphoma, myeloma and breast cancer who were scheduled to receive autologous PBSC transplantation. PBSC collection was performed following mobilization with subcutaneous G-CSF at 5-10 microg/kg/day. A minimum target of 2 x 10(6)/kg CD34+ cells was considered an acceptable harvest to ensure a safe transplant. On average, three aphereses per patient were performed and a total of 204 apheresis samples were analyzed. Regression analysis of the percentage and absolute number of CD34+ cells, as calculated with each method, achieved an excellent correlation in spite of methodological differences. In fact, both CD34+dim and CD34+CD45- events were included in our gating strategy. In the setting of a triple staining associating CD34, CD38 and CD45, we identified a variable fraction of CD34+CD38+CD45- cells which would be otherwise undetected due to its CD45 negativity. To this end, we used a new technology referred to as laser-scanning cytometry (LSC) which allowed the isolation and morphological identification of CD34+CD45- cells. By comparing CD34+CD45+ and CD34+CD45- cells, we found that they share a common morphology, thus confirming the hypothesis that the latter are to be considered for CD34+ cell calculation. The median number of CD34+ cells/kg, as calculated by the three methods, was: 4.79 x 10(6)/kg (range 1-570) for the Milan/Mulhouse protocol, 3.9 x 10(6)/kg (range 0.8-498) for the ISHAGE one, and 5.17 x 10(6)/kg (range 2-599) for our protocol. The median time to ANC and PLT engraftment was 11 (range 9-24) and 20 (range 10-70) days, respectively. Our protocol achieved the best correlation between CD34+ cells/kg and time to ANC/PLT recovery according to the Spearman's rank test (r = -40 and P < 0. 015 for ANC, r= -46 and P = 0.005 for PLT). We conclude that (1) CD45 does not appear the ideal partner of HPCA-2 for determination of hematopoietic progenitors in mobilized peripheral blood; and (2) for clinical application, a single staining with 8G12 appears simple, reliable and feasible when rigorous procedures for sample preparation and acquisition are followed and an adequate software for multiparametric analysis is available.
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PMID:Enumeration of CD34+ hematopoietic progenitor cells for clinical transplantation: comparison of three different methods. 1055 63

The myelomagenic capacity of clonotypic myeloma cells in G-CSF mobilized blood was tested by xenotransplant. Intracardiac (IC) injection of NOD SCID mice with peripheral cells from 5 patients who had aggressive myeloma led to lytic bone lesions, human Ig in the serum, human plasma cells, and a high frequency of clonotypic cells in the murine bone marrow (BM). Human B and plasma cells were detected in BM, spleen, and blood. Injection of ex vivo multiple myeloma cells directly into the murine sternal BM (intraosseus injection [IO]) leads to lytic bone lesions, BM plasma cells, and a high frequency of clonotypic cells in the femoral BM. This shows that myeloma has spread from the primary injection site to distant BM locations. By using a cellular limiting dilution PCR assay to quantify clonotypic B lineage cells, we confirmed that peripheral myeloma cells homed to the murine BM after IC and IO injection. The myeloma progenitor undergoes self-renewal in murine BM, as demonstrated by the transfer of human myeloma to a secondary recipient mouse. For 6 of 7 patients, G-CSF mobilized cells from patients who have minimal disease, taken at the time of mobilization or after cryopreservation, included myeloma progenitors as identified by engraftment of clonotypic cells and/or lytic bone disease in mice. This indicates that myeloma progenitors are mobilized into the blood by cyclophosphamide/G-CSF. Their ability to generate myeloma in a xenotransplant model implies that such progenitors are also myelomagenic when reinfused into patients, and suggests the need for an effective strategy to purge them before transplant.
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PMID:Myeloma progenitors in the blood of patients with aggressive or minimal disease: engraftment and self-renewal of primary human myeloma in the bone marrow of NOD SCID mice. 1064 22

Multiple myeloma (MM) is characterized by the expansion of tumor plasma cells in bone marrow (BM), but neoplastic cells have been consistently detected in peripheral blood (PB). Peripheral blood progenitor cell (PBPC) collections have been widely used to support high-dose therapy for MM patients. A flow cytometric technique has been used to detect plasma cells in PB and PBPC harvests. High CD38 expression identified these cells, and their nature was confirmed by the coexpression of specific antigens, such as CD138 and cytoplasmic immunoglobulins. Malignant plasma cell reinfusion could negatively affect response rate and survival, as demonstrated in other hematological malignancies. To address this issue, the relationship between the number of reinfused plasma cells, response to chemotherapy and event-free survival (EFS) have been analyzed. Sixty-four MM patients were treated with intensified chemotherapy at diagnosis. They were mobilized with cyclophosphamide and G-CSF, and then treated with melphalan 100 mg/m2 (MEL100) followed by PBPC support. A second course was given after 2 months, and a third to patients not in complete remission. There was no correlation between the number of reinfused plasma cells and response rate after this intensified chemotherapy: patients attaining complete remission received 3.6 x 106/kg CD38+ cells, while those with a partial or no response received 5.6 and 2.9 x 106/kg CD38+ cells. Similarly, there was no correlation between the number of reinfused plasma cells and EFS. Patients receiving less than 4.85 x 106/kg CD38+ cells experienced a median EFS of 34.2 months as opposed to 36.4 months for those receiving more than 4.85 x 106/kg CD38+ cells (P = 0.7). Recurrence of the disease is consistently observed in MM: our data suggest that in vivo residual tumor cells, rather than reinfused plasma cells are more likely to be responsible for relapse. Bone Marrow Transplantation (2000) 25, 25-29.
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PMID:Multiple myeloma: the number of reinfused plasma cells does not influence outcome of patients treated with intensified chemotherapy and PBPC support. 1065 10

Thirty-seven patients with multiple myeloma (stage II and III, 65% increased beta2-microglobulin level) were prospectively treated with a median of 3.7 VAD courses (range 2-8) followed by cyclophosphamide (6 g/m2) in conjunction with G-CSF (5 microg/kg filgrastrim (n = 14), or 3.5 microg/kg lenograstrim (n = 22)), and peripheral stem cell (PSC) isolation. After regeneration this was followed by one EDAP course and high-dose melphalan (HDM, 200 mg/m2) in combination with re-infusion of PSC. Adequate stem cell mobilization was obtained with both G-CSF regimens. A median of 41x10(6) CD34+ cells/kg (range 4.5-161) was collected in a median of 1.6 leukapheresis procedures following filgrastrim (n = 14) and 24x10(6) CD34+ cells/kg (range 2. 3-80) in a median of 1.7 leukapheresis procedures following lenograstrim (n = 22) which indicated no significant difference (P = 0.24) between both G-CSF regimens. A rapid hematological recovery was obtained after HDM with reinfusion of a median of 9.3x10(6) CD34+ cells/kg. After the total courses the overall response was 84% with a complete remission rate of 30%. Currently the median overall survival is 44.0 months (95% CI 38.9-49.1) with a median follow-up of 33 months (range 3-51) and a median event-free survival of 29.0 months (95% CI 25.3-32.7) (n = 33). Post transplantation a high incidence of oligloclonal serum immunoglobulins (Igs) was observed. In 73% of the patients new oligoclonal or monoclonal serum bands were noticed 3 months post transplantation. IgG-lambda and IgG-kappa bands predominated. In 48% of the cases the oligoclonal Igs disappeared after a median follow-up of 22 months (range 8-36), whereas in 52% of the cases the oligoclonal Igs persisted with a median follow-up of 31 months (range 21-45), which did not correlate with a significant difference in overall, and event-free survival between both subgroups.
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PMID:Autologous stem cell transplantation in multiple myeloma after VAD and EDAP courses: a high incidence of oligoclonal serum Igs post transplantation. 1074 57

flt3-ligand (flt3-L) is a very effective mobilizer of hematopoietic stem cells (HSC) and is capable of inducing multilineage hematopoietic cell differentiation both in vivo and in vitro. We measured, by ELISA, the plasma peripheral blood flt3-L concentrations in 28 non-Hodgkin's lymphoma (NHL) patients before and after mobilization with three different mobilization regimens, including priming with cyclophosphamide (CY) plus G-CSF, CY plus GM-CSF, and CY plus GM-CSF (8 days) followed by G-CSF. We also determined the levels of flt3-L in the peripheral blood during four apheresis collections and 6 months after transplantation. The steady-state level of flt3-L in NHL patients (n = 18) who mobilized > or =2 x 10(6) CD34+ cells/kg in four apheresis collections was 34 +/- 4 pg/ml and was similar to the levels observed in 10 normal controls (27 +/- 7, p = 0.1) regardless of the mobilization protocol used. In contrast, patients who failed to mobilize a total of >0.4 x 10(6) CD34+ cells/kg in two consecutive apheresis collections (n = 10) had flt3-L levels of 106 +/- 11 pg/ml, significantly higher (p = 0.006) than that of the good mobilizers group, regardless of the mobilization protocol used. Similar results were observed in 29 multiple myeloma (MM) patients. A mean of 23.8 +/- 7.9 pg/ml and 450 +/- 85 pg/ml flt3-L was obtained in the good mobilizers (n = 24) and the nonmobilizers (n = 5) groups of patients, respectively. Statistical analysis revealed a significant difference (p = 0.0006) between the two groups of MM patients, but no correlation was observed between the levels of flt3-L and CD34+ cell/microl, in mobilized peripheral blood. Our results also suggest that measurement of plasma levels of flt3-L before mobilization can be clinically useful to predict for patients with poor mobilization outcome.
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PMID:High steady-state plasma levels of flt3-ligand in the peripheral blood is a good predictor for poor mobilization of CD34+ PBSC in patients undergoing high-dose chemotherapy and stem cell rescue. 1081 43

Between August 1991 and December 1998, 400 patients (lymphomas: 197; acute leukemia: 86; multiple myeloma: 70 and solid tumors: 47) were admitted for autologous transplantation. All patients were mobilized with chemotherapy plus G-CSF. The hematological recovery was similar in all disease groups. Patients with acute leukemias and multiple myeloma had a slower platelet recovery. Treatment-related death was 4.5%. The status of the disease at diagnosis was the most significant prognostic factor. With a median follow-up of 23 months the probability of event-free survival at 60 months was 46% for low grade lymphoma, 44% for intermediate and high grade lymphoma, 58% for Hodgkin's disease, 45% for acute myeloblastic leukemia, 38% for solid tumors and 15% for multiple myeloma. The probability of survival at 60 months was 67% for low grade lymphoma, 47% for intermediate and high grade lymphoma, 75% for Hodgkin's disease, 52% for acute myeloblastic leukemia, 54% for solid tumors and 25% for multiple myeloma. It can be concluded that autologous progenitor cell transplantation induces a complete and faster hematological recovery in all groups of patients without any late graft failure. Results are similar to those published in the literature. The treatment-related death was low and acceptable.
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PMID:[Eight years of experience in a single institution in hematopoietic stem cell autologous transplantation in malignant hematological diseases and in solid tumors]. 1083 8


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