Ex vivo expanded peripheral blood progenitor cells provide rapid neutrophil recovery after high-dose chemotherapy in patients with breast cancer

Blood ◽  
2000 ◽  
Vol 96 (9) ◽  
pp. 3001-3007 ◽  
Author(s):  
Ian McNiece ◽  
Roy Jones ◽  
Scott I. Bearman ◽  
Pablo Cagnoni ◽  
Yago Nieto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Ex Vivo ◽  
High Dose Chemotherapy ◽  
Control Group ◽  
High Dose ◽  
Platelet Recovery ◽  
Peripheral Blood Progenitor Cells ◽  
Neutrophil Engraftment

Ex vivo expanded peripheral blood progenitor cells (PBPCs) have been proposed as a source of hematopoietic support to decrease or eliminate the period of neutropenia after high-dose chemotherapy. CD34 cells were selected from rhG-CSF mobilized PBPCs from patients with breast cancer and were cultured for 10 days in defined media containing 100 ng/mL each of rhSCF, rhG-CSF, and PEG-rhMGDF in 1 L Teflon bags at 20 000 cells/mL. After culture the cells were washed and reinfused on day 0 of transplantation. On day +1, cohort 1 patients (n = 10) also received an unexpanded CD34-selected PBPC product. These patients engrafted neutrophils (absolute neutrophil count, >500/μL) in a median of 6 (range, 5-14) days. Cohort 2 patients (n = 11), who received expanded PBPCs only, engrafted neutrophils in a median of 8 (range, 4-16) days. In comparison, the median time to neutrophil engraftment in a historical control group of patients (n = 100) was 9 days (range, 7-30 days). All surviving patients are now past the 15-month posttransplantation stage with no evidence of late graft failure. The total number of nucleated cells harvested after expansion culture was shown to be the best predictor of time to neutrophil engraftment, with all patients receiving more than 4 × 107 cells/kg, engrafting neutrophils by day 8. No significant effect on platelet recovery was observed in any patient. These data demonstrate that PBPCs expanded under the conditions defined can shorten the time to engraftment of neutrophils compared with historical controls and that the rate of engraftment is related to the dose of expanded cells transplanted.

Ex vivo expanded peripheral blood progenitor cells provide rapid neutrophil recovery after high-dose chemotherapy in patients with breast cancer

Blood ◽  
2000 ◽  
Vol 96 (9) ◽  
pp. 3001-3007 ◽  
Author(s):  
Ian McNiece ◽  
Roy Jones ◽  
Scott I. Bearman ◽  
Pablo Cagnoni ◽  
Yago Nieto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Ex Vivo ◽  
High Dose Chemotherapy ◽  
Control Group ◽  
High Dose ◽  
Platelet Recovery ◽  
Peripheral Blood Progenitor Cells ◽  
Neutrophil Engraftment

Abstract Ex vivo expanded peripheral blood progenitor cells (PBPCs) have been proposed as a source of hematopoietic support to decrease or eliminate the period of neutropenia after high-dose chemotherapy. CD34 cells were selected from rhG-CSF mobilized PBPCs from patients with breast cancer and were cultured for 10 days in defined media containing 100 ng/mL each of rhSCF, rhG-CSF, and PEG-rhMGDF in 1 L Teflon bags at 20 000 cells/mL. After culture the cells were washed and reinfused on day 0 of transplantation. On day +1, cohort 1 patients (n = 10) also received an unexpanded CD34-selected PBPC product. These patients engrafted neutrophils (absolute neutrophil count, >500/μL) in a median of 6 (range, 5-14) days. Cohort 2 patients (n = 11), who received expanded PBPCs only, engrafted neutrophils in a median of 8 (range, 4-16) days. In comparison, the median time to neutrophil engraftment in a historical control group of patients (n = 100) was 9 days (range, 7-30 days). All surviving patients are now past the 15-month posttransplantation stage with no evidence of late graft failure. The total number of nucleated cells harvested after expansion culture was shown to be the best predictor of time to neutrophil engraftment, with all patients receiving more than 4 × 107 cells/kg, engrafting neutrophils by day 8. No significant effect on platelet recovery was observed in any patient. These data demonstrate that PBPCs expanded under the conditions defined can shorten the time to engraftment of neutrophils compared with historical controls and that the rate of engraftment is related to the dose of expanded cells transplanted.

Ex vivo expanded unselected peripheral blood: progenitor cells reduce posttransplantation neutropenia, thrombocytopenia, and anemia in patients with breast cancer

Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2385-2390 ◽  
Author(s):  
Ronald L. Paquette ◽  
Sanaa T. Dergham ◽  
Ellen Karpf ◽  
He-Jing Wang ◽  
Dennis J. Slamon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Ex Vivo ◽  
Conditioning Regimen ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cell Dose ◽  
Development Factor ◽  
Peripheral Blood Progenitor Cells

The safety and efficacy of administering ex vivo expanded peripheral blood progenitor cells (PBPC) to patients with breast cancer who undergo high-dose chemotherapy and PBPC transplantation was investigated. Unselected PBPC were cultured in gas-permeable bags containing 1-L serum-free media, granulocyte colony-stimulating factor, stem cell factor, and pegylated megakaryocyte growth and development factor for 9 days. Cell dose cohorts were assigned to have between 2 and 24 × 109 PBPC cultured at 1, 2, or 3 × 106 cells/mL. Twenty-four patients received high-dose chemotherapy followed by infusion of the cultured PBPC and at least 5 × 106 CD34+ uncultured cryopreserved PBPC per kilogram. No toxicities resulted from infusions of the ex vivo expanded PBPC. The study patients had shorter times to neutrophil (P = .0001) and platelet (P = .01) recovery and fewer red cell transfusions (P = .02) than 48 historical controls who received the same conditioning regimen and posttransplantation care and at least 5 × 106CD34+ PBPC per kilogram. Improvements in all these endpoints were significantly correlated with the expanded cell dose. Nine of 24 (38%) patients recovered neutrophil counts above 500/μL by day 5 or 6 after transplantation, whereas none of the controls had neutrophil recovery before the eighth day. Seven (29%) patients had neutropenia for 3 or fewer days, and 9 (38%) patients did not experience neutropenic fevers or require broad-spectrum antibiotics. Therefore, ex vivo expanded PBPC are capable of ameliorating posttransplantation neutropenia, thrombocytopenia, and anemia in patients receiving high-dose chemotherapy.

Ex vivo expanded unselected peripheral blood: progenitor cells reduce posttransplantation neutropenia, thrombocytopenia, and anemia in patients with breast cancer

Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2385-2390 ◽  
Author(s):  
Ronald L. Paquette ◽  
Sanaa T. Dergham ◽  
Ellen Karpf ◽  
He-Jing Wang ◽  
Dennis J. Slamon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Ex Vivo ◽  
Conditioning Regimen ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cell Dose ◽  
Development Factor ◽  
Peripheral Blood Progenitor Cells

Abstract The safety and efficacy of administering ex vivo expanded peripheral blood progenitor cells (PBPC) to patients with breast cancer who undergo high-dose chemotherapy and PBPC transplantation was investigated. Unselected PBPC were cultured in gas-permeable bags containing 1-L serum-free media, granulocyte colony-stimulating factor, stem cell factor, and pegylated megakaryocyte growth and development factor for 9 days. Cell dose cohorts were assigned to have between 2 and 24 × 109 PBPC cultured at 1, 2, or 3 × 106 cells/mL. Twenty-four patients received high-dose chemotherapy followed by infusion of the cultured PBPC and at least 5 × 106 CD34+ uncultured cryopreserved PBPC per kilogram. No toxicities resulted from infusions of the ex vivo expanded PBPC. The study patients had shorter times to neutrophil (P = .0001) and platelet (P = .01) recovery and fewer red cell transfusions (P = .02) than 48 historical controls who received the same conditioning regimen and posttransplantation care and at least 5 × 106CD34+ PBPC per kilogram. Improvements in all these endpoints were significantly correlated with the expanded cell dose. Nine of 24 (38%) patients recovered neutrophil counts above 500/μL by day 5 or 6 after transplantation, whereas none of the controls had neutrophil recovery before the eighth day. Seven (29%) patients had neutropenia for 3 or fewer days, and 9 (38%) patients did not experience neutropenic fevers or require broad-spectrum antibiotics. Therefore, ex vivo expanded PBPC are capable of ameliorating posttransplantation neutropenia, thrombocytopenia, and anemia in patients receiving high-dose chemotherapy.

Effect of peripheral-blood progenitor cells mobilised by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy

The Lancet ◽  
1992 ◽  
Vol 339 (8794) ◽  
pp. 640-644 ◽  
Author(s):  
W.P. Sheridan ◽  
R.M. Fox ◽  
C.G. Begley ◽  
D. Maher ◽  
K.M. McGrath ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Peripheral Blood ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Platelet Recovery ◽  
Peripheral Blood Progenitor Cells

scholarly journals Maintenance of transplantation potential in ex vivo expanded CD34(+)- selected human peripheral blood progenitor cells

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 2898-2903 ◽  
Author(s):  
R Henschler ◽  
W Brugger ◽  
T Luft ◽  
T Frey ◽  
R Mertelsmann ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Peripheral Blood ◽  
Large Scale ◽  
Ex Vivo ◽  
Human Peripheral Blood ◽  
Ex Vivo Expansion ◽  
High Dose ◽  
Peripheral Blood Progenitor Cells ◽  
Limiting Dilution

Abstract CD34(+)-selected hematopoietic progenitor cells are being increasingly used for autotransplantation, and recent evidence indicates that these cells can be expanded ex vivo. Of 15 patients with solid tumors undergoing a phase I/II clinical trial using CD34(+)-selected peripheral blood progenitor cells (PBPCs) after high-dose chemotherapy, we analyzed the frequency of long-term culture-initiating cells (LTCIC) as a measure of transplantation potential before and after ex vivo expansion of CD34+ cells. PBPCs were mobilized by combination chemotherapy and granulocyte colony-stimulating factor (G-CSF). The original unseparated leukapheresis preparations, the CD34(+)-enriched transplants, as well as nonabsorbed fractions eluting from the CD34 immunoaffinity columns (Ceprate; CellPro, Bothell, WA) were monitored for their capacity to repopulate irradiated allogeneic stroma in human long-term bone marrow cultures. We found preservation of more than three quarters of fully functional LTCIC in the CD34(+)-selected fractions. Quantitation of LTCIC by limiting dilution analysis showed a 53-fold enrichment of LTCIC from 1/9,075 in the unseparated cells to an incidence of 1/169 in the CD34+ fractions. Thus, in a single apheresis, it was possible to harvest a median of 1.65 x 10(4) LTCIC per kg body weight (range, 0.71 to 3.72). In addition, in six patients, large-scale ex vivo expansions were performed using a five-factor cytokine combination consisting of stem cell factor (SCF), interleukin-1 (IL-1), IL-3, IL-6, and erythropoietin (EPO), previously shown to expand committed progenitor cells. LTCIC were preserved, but not expanded during the culture period. Optimization of ex vivo expansion growth factor requirements using limiting dilution assays for LTCIC estimation indicated that the five-factor combination using SCF, IL-1, IL-3, IL-6, and EPO together with autologous plasma was the most reliable combination securing both high progenitor yield and, at the same time, optimal preservation of LTCIC. Our data suggest that ex vivo-expanded CD34+ PBPCs might be able to allow long-term reconstitution of hematopoiesis.

scholarly journals Granulocyte colony-stimulating factor "mobilized" peripheral blood progenitor cells accelerate granulocyte and platelet recovery after high-dose chemotherapy

Blood ◽  
1993 ◽  
Vol 81 (8) ◽  
pp. 2031-2035 ◽  
Author(s):  
NJ Chao ◽  
JR Schriber ◽  
K Grimes ◽  
GD Long ◽  
RS Negrin ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Peripheral Blood ◽  
High Dose ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Growth Factors ◽  
Platelet Recovery ◽  
Peripheral Blood Progenitor Cells ◽  
Significant Difference ◽  
Stimulating Factor

Abstract Hematopoietic growth factors have been used to accelerate engraftment after bone marrow transplantation and to “mobilize” peripheral blood progenitor cells (PBPC). We report on the data in 85 consecutive patients with Hodgkin's disease who were treated in a single institution using different methods to obtain PB progenitor cells. Use of granulocyte colony-stimulating factor for mobilization resulted in a significantly accelerated time to recovery of granulocytes (10 days v 12 days, P < .01) when compared with “nonmobilized” PBPC recipients. Similarly, use of mobilized PBPC resulted in a significantly accelerated time to platelet engraftment (13 days v 30 days, P < .001) when compared with “nonmobilized” recipients. Moreover, there was a statistically significant difference in total costs in favor of the group receiving “mobilized” PBPC.

Sign in / Sign up

Export Citation Format

Share Document