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Leukemia Feb 2003The objective of our study was to determine the effect of adding r-metHuSCF to Filgrastim and cyclophosphamide for mobilization of peripheral blood progenitor cells... (Clinical Trial)
Clinical Trial
Mobilization of peripheral blood progenitor cells with a combination of cyclophosphamide, r-metHuSCF and filgrastim in patients with breast cancer previously treated with chemotherapy.
The objective of our study was to determine the effect of adding r-metHuSCF to Filgrastim and cyclophosphamide for mobilization of peripheral blood progenitor cells (PBPC), on collection of CD34(+) cells and engraftment after autologous stem cell transplant. Twenty-three patients with previously treated stage II-IV breast cancer received cyclophosphamide (3 g/m(2)), Filgrastim 5 microg/kg daily and r-metHuSCF 20 microg/kg daily. Two PBPC collections were performed on consecutive days starting the day the WBC count was above 7.5 x 10(3)/microl. Collection was performed between days +9 and +12 and the median number of CD34(+) cells collected was 9.9 x 10(6)/kg (1.1-53.1) and 6.6 x 10(6)/kg (1.4-33.8) for the first and second apheresis, respectively. Despite being previously treated patients, the target CD34(+) cell dose required for SCT was obtained in all patients. SCT was associated with rapid neutrophil and platelet engraftment and a highly significant correlation was observed between the number of CD34(+) cells infused and engraftment. Treatment with SCF plus filgrastim was well tolerated, with mild to moderate local skin rash being the most frequently reported adverse event. In conclusion, addition of r-metHuSCF induces mobilization of a large number of CD34(+) cells which results in shortening of time to engraftment and hospitalization.
Topics: Adult; Aged; Breast Neoplasms; Cyclophosphamide; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cells; Humans; Lymphatic Metastasis; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Recombinant Proteins; Stem Cell Factor; Stem Cell Transplantation; Transplantation, Autologous; Treatment Outcome
PubMed: 12592344
DOI: 10.1038/sj.leu.2402750 -
Leukemia Research Mar 2003Transplantation with unrelated umbilical cord blood (UCB) is marked by delayed hematologic recovery. This report summarizes two adults with chronic myelogenous leukemia... (Clinical Trial)
Clinical Trial
Hematopoietic recovery after unrelated umbilical cord-blood allogeneic transplantation in adults treated with in vivo stem cell factor (R-MetHuSCF) and filgrastim administration.
Transplantation with unrelated umbilical cord blood (UCB) is marked by delayed hematologic recovery. This report summarizes two adults with chronic myelogenous leukemia (CML), who received myeloablative conditioning followed by infusion of a non-expanded single UCB graft. These CML patients were enrolled in a clinical trial incorporating concomitant in vivo administration of stem cell factor (R-MetHuSCF) and filgrastim from day of UCB infusion until attained hematopoietic recovery. Each patient engrafted fully with donor UCB, with days to absolute neutrophil count (ANC) >500/microl being 13 and 29 days, respectively. Both patients remain in cytogenetic remission at 28 months follow-up. 'In vivo UCB expansion' with administration of concomitant R-MetHuSCF and filgrastim may facilitate prompt hematologic engraftment.
Topics: Adult; Cord Blood Stem Cell Transplantation; Drug Therapy, Combination; Filgrastim; Graft Survival; Granulocyte Colony-Stimulating Factor; Hematopoiesis; Histocompatibility; Histocompatibility Testing; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Middle Aged; Myeloablative Agonists; Recombinant Proteins; Stem Cell Factor; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome
PubMed: 12537973
DOI: 10.1016/s0145-2126(02)00090-5 -
Bone Marrow Transplantation Dec 2002Patients (n = 69) with multiple myeloma undergoing peripheral blood stem cell collection (PBSC) were treated with cyclophosphamide and a combination of recombinant... (Clinical Trial)
Clinical Trial
Optimising parameters for peripheral blood leukapheresis after r-metHuG-CSF (filgrastim) and r-metHuSCF (ancestim) in patients with multiple myeloma: a temporal analysis of CD34(+) absolute counts and subsets.
Patients (n = 69) with multiple myeloma undergoing peripheral blood stem cell collection (PBSC) were treated with cyclophosphamide and a combination of recombinant methionyl human granulocyte colony-stimulating factor (r-metHuG-CSF, filgrastim) and recombinant methionyl human stem cell factor (r-metHuSCF, ancestim). The objectives of this study were to determine: (1) The proportion of patients reaching a target yield of >or=5 x 10(6) CD34(+) cells/kg in one or two successive large-volume (20 liter) leukapheresis procedures; (2) the optimal collection time for leukapheresis; (3) mobilization kinetics of CD34(+) subsets in response to G-CSF/SCF. All patients were mobilized with cyclophosphamide (2.5 g/m(2)) on day 0 followed by filgrastim (10 microg/kg ) plus ancestim (20 microg/kg) commencing day 1 and continuing to day 11 or 12. Of the 65 evaluable patients, 57 were considered not heavily pretreated and 96.5% obtained a target of >or=5 x 10(6)/kg in one collection. The median CD34(+) cells/kg was 39.5 x 10(6) (range: 5.2-221.2 x 10(6)). Subset analysis demonstrated the number of CD38(-), CD33(-), and CD133(+) peaked at day 11; and CD34(+), CD90(+) cells peaked at day 10. The optimum day for leukapheresis was determined to be day 11. The median absolute peripheral blood CD34(+) cell numbers on day 11 was 665 x 10(6)/l (range: 76-1481 x 10(6)/l). Eight of the 10 heavily pretreated patients were evaluable: three achieved the target dose in one leukapheresis (37.5%) and three (37.5%) achieved the target dose with two leukaphereses. Use of this mobilization strategy allowed the collection of high numbers of CD34(+) cells and early progenitors and the ability to predictably schedule leukapheresis.
Topics: Adult; Aged; Antigens, CD34; Blood Cell Count; Cyclophosphamide; Female; Filgrastim; Flow Cytometry; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cells; Humans; Immunophenotyping; Leukapheresis; Male; Middle Aged; Multiple Myeloma; Recombinant Proteins; Stem Cell Factor
PubMed: 12476276
DOI: 10.1038/sj.bmt.1703765 -
Lancet (London, England) Oct 2000We observed an unexpectedly rapid rise in platelet counts with complete haematological recovery after a BEAM regimen, in a patient who could not be rescued by autologous...
We observed an unexpectedly rapid rise in platelet counts with complete haematological recovery after a BEAM regimen, in a patient who could not be rescued by autologous transplant but who received filgrastim, epoetin alfa, and ancestim. We feel that these results may be attributed to this specific growth factor combination, including ancestim, a cytokine known to act on primitive stem cells. If confirmed, this observation may open new possibilities in intensive chemotherapy for patients for whom haematopoietic progenitors are difficult to harvest. This may also represent an alternative to ex-vivo expansion and deserves further investigation.
Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Blood Cell Count; Carmustine; Cytarabine; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Etoposide; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoiesis; Hematopoietic Cell Growth Factors; Humans; Lymphoma, Non-Hodgkin; Melphalan; Platelet Transfusion; Recombinant Proteins; Treatment Outcome
PubMed: 11073025
DOI: 10.1016/S0140-6736(00)02820-8 -
Clinical Cancer Research : An Official... Sep 1997The quantity of hematopoietic progenitors in an apheresis collection is defined by the number of CD34(+) cells or granulocyte macrophage colony-forming units present....
The quantity of hematopoietic progenitors in an apheresis collection is defined by the number of CD34(+) cells or granulocyte macrophage colony-forming units present. These parameters are believed to give roughly equivalent information on graft quality. We here report that the in vitro proliferative potential of r-metHuSCF (stem cell factor) plus filgrastim (granulocyte colony-stimulating factor; r-metHuG-CSF) mobilized peripheral blood (PB) CD34(+) cells obtained from previously heavily treated non-Hodgkin's lymphoma patients inversely correlates with extent of prior therapy. CD34(+) cells were enriched using the CellPro Ceprate system and placed in liquid culture for 4 weeks in the presence of either r-metHuSCF, IL-3, IL-6, filgrastim (S36G), or S36G plus erythropoietin (S36GE) with a weekly exchange of media and cytokines with reestablishment of culture at the starting cell concentration (Delta assay) and enumeration of progenitors. Starting with 4 x 10(4) CD34(+) cells from apheresis samples from patients who had received <10 cycles of prior chemotherapy, progenitors were detectable in culture at 4 weeks 81% of the time as compared to 14% with CD34(+) cells from patients who had received >10 cycles and 5% for >10 cycles plus radiotherapy. The total number of progenitors generated over the duration of culture (area under the curve) was calculated using the trapezoidal rule as a novel measure of the proliferative potential of the enriched PB CD34(+) cell population. The median area under the curve of CD34(+) cells from patients receiving <10 cycles of prior chemotherapy was 7.4 and 5.7 (x10(5)) using S36G or S36GE, respectively, 1.8 and 1.9 if the patients received >10 cycles of prior chemotherapy, and 1.4 and 1.2 if the patients received >10 cycles of prior chemotherapy plus radiotherapy (P < 0.001). These data show that prior therapy impacts on the quality of PB CD34(+) cells as measured by their ability to generate committed progenitors over a number of weeks in liquid culture.
Topics: Antigens, CD34; Area Under Curve; Cell Division; Colony-Forming Units Assay; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Interleukin-3; Interleukin-6; Leukapheresis; Lymphoma, Non-Hodgkin; Recombinant Proteins; Stem Cell Factor
PubMed: 9815845
DOI: No ID Found -
Blood May 1997To examine the safety and efficacy of recombinant-methionyl human stem cell factor (r-metHuSCF), 38 patients with intermediate-grade or immunoblastic high-grade... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Recombinant methionyl human stem cell factor and filgrastim for peripheral blood progenitor cell mobilization and transplantation in non-Hodgkin's lymphoma patients--results of a phase I/II trial.
To examine the safety and efficacy of recombinant-methionyl human stem cell factor (r-metHuSCF), 38 patients with intermediate-grade or immunoblastic high-grade non-Hodgkin's lymphoma who were eligible for autologous transplantation were randomized to receive r-metHuSCF (5, 10, 15, or 20 microg/kg/d) plus Filgrastim (10 microg/kg/d) or Filgrastim (10 microg/kg/d) alone to mobilize peripheral blood progenitor cells. Subcutaneous administration of r-metHuSCF was well tolerated in conjunction with a multi-agent pre-medication regimen; local injection site reactions were the most commonly seen adverse event. The total mononuclear cell count, CD34+ cell content, granulocyte-macrophage colony-forming cells (GM-CFC), and burst-forming units-erythroid (BFU-E) per kilogram in the apheresis product was similar when all patients were analyzed by treatment cohort and mobilization regimen (Filgrastim or r-metHuSCF in combination with Filgrastim); however, when prior chemotherapy was taken into account in a supplementary analysis, clinically important differences were observed. Extensive prior therapy was defined as the amount of exposure to specific stem cell toxic chemotherapeutic agents that patients received. These agents include procarbazine, nitrogen mustard, melphalan, nitrosoureas (> or = 2 cycles of any of these drugs) or greater than 7.5 g of cytosine arabinoside. In these patients, there was an increased number of CD34+ cells (1.76 v 0.28 x 10(6)/kg), GM-CFC (20.5 v 5.0 x 10(4)/kg), and BFU-E (36.9 v 8.9 x 10(4)/kg) in patients receiving r-metHuSCF and Filgrastim (N = 18) compared with Filgrastim alone (N = 5). These patients also had a decreased time to an untransfused platelet count of 20 x 10(9)/L that was 10.5 days shorter in the patients who received r-metHuSCF and Filgrastim (12.5 v 23 days). These differences were not found to be statistically significant, possibly because of small size, but are clinically important.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Colony-Forming Units Assay; Cyclophosphamide; Drug Therapy, Combination; Etoposide; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematopoiesis; Hematopoietic Stem Cells; Humans; Leukapheresis; Leukocyte Count; Lymphoma, Non-Hodgkin; Male; Middle Aged; Recombinant Proteins; Stem Cell Factor
PubMed: 9129016
DOI: No ID Found