The Use of G-CSF or GM-CSF Mobilized Peripheral Blood Progenitor Cells (PBPC) Alone or to Augment Marrow as Hematologic Support of Single or Multiple Cycle High-Dose Chemotherapy

1993 ◽  
Vol 2 (3) ◽  
pp. 377-382 ◽  
Author(s):  
ANTHONY D. ELIAS ◽  
LOIS AYASH ◽  
ISIDORE TEPLER ◽  
CATHERINE WHEELER ◽  
GARY SCHWARTZ ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Peripheral Blood ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Gm Csf ◽  
Peripheral Blood Progenitor Cells ◽  
Multiple Cycle ◽  
Mobilized Peripheral Blood

In Vitro Manipulation of Peripheral Blood Progenitor Cell Collections

1998 ◽  
Vol 21 (6_suppl) ◽  
pp. 1-10
Author(s):  
C. Carlo-Stella ◽  
V. Rizzoli
Keyword(s):  
Progenitor Cells ◽  
Peripheral Blood ◽  
Progenitor Cell ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Peripheral Blood Progenitor Cells ◽  
Stem And Progenitor Cells ◽  
Therapy Strategies ◽  
Mobilized Peripheral Blood

Mobilized peripheral blood progenitor cells (PBPC) are increasingly used to reconstitute hematopoiesis in patients undergoing high-dose chemoradiotherapy. PBPC collections comprise a heterogeneous population containing both committed progenitors and pluripotent stem cells and can be harvested (i) in steady state, (ii) after chemotherapeutic conditioning, (iii) growth factor priming, or (iv) both. The use of PBPC has opened new therapeutic perspectives mainly related to the availability of large amounts of mobilized hematopoietic stem and progenitor cells. Extensive manipulation of the grafts, including the possibility of exploiting these cells as vehicles for gene therapy strategies, are now possible and will be reviewed.

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.

Use of peripheral-blood progenitor cells abrogates the myelotoxicity of repetitive outpatient high-dose carboplatin and cyclophosphamide chemotherapy.

1993 ◽  
Vol 11 (8) ◽  
pp. 1583-1591 ◽  
Author(s):  
I Tepler ◽  
S A Cannistra ◽  
E Frei ◽  
R Gonin ◽  
K C Anderson ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Peripheral Blood ◽  
Disease Onset ◽  
Dose Intensity ◽  
Outpatient Setting ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Intensive Chemotherapy ◽  
Gm Csf ◽  
Peripheral Blood Progenitor Cells

PURPOSE Attempts to increase dose-intensity in clinical practice have been limited by cumulative hematologic toxicity despite the use of hematopoietic growth factors. To address this problem, we designed a study to determine whether four cycles of dose-intensive chemotherapy with carboplatin could be administered in the outpatient setting using granulocyte-macrophage colony-stimulating factor (GM-CSF) and peripheral-blood progenitor cells (PBPCs) that had been harvested before initiation of treatment. PATIENTS AND METHODS An initial cycle (cycle no. 0) of cyclophosphamide 4 g/m2 followed by GM-CSF was used to mobilize PBPCs harvested by leukapheresis for 6 consecutive days. Cycles no. 1 through 4 consisted of outpatient carboplatin 600 mg/m2 and cyclophosphamide 600 mg/m2 followed by GM-CSF 5 micrograms/kg subcutaneously (SC) twice per day every 28 days. In cycle no. 1, PBPC were not reinfused to assess the effects of GM-CSF alone. In cycles no. 2 through 4, PBPCs were reinfused on day 3 in an outpatient setting. RESULTS In eight assessable patients, the addition of PBPCs in cycle no. 2 resulted in a significant reduction in the median duration of thrombocytopenia less than 20,000/microL (6.5 v 1 day; P = .016), days to platelets more than 50,000/microL (20.5 v 15 days; P = .020), number of platelet transfusions (five v 1.5; P = .016), and duration of neutropenia (absolute neutrophil count [ANC] < 1,000/microL (7 v 2.5 days; P = .008) when compared with cycle no. 1. Dose-limiting hematologic toxicity, defined as more than 7 days of platelets less than 20,000/microL or ANC less than 500/microL, was observed in four of eight patients during cycle no. 1, but not during cycles no. 2, 3, and 4 of chemotherapy supported by PBPCs (a total of 19 cycles in eight patients). Five of eight patients completed all four cycles of high-dose therapy. Three patients did not complete four cycles due to late thrombocytopenia (n = 2) or tumor progression (n = 1). CONCLUSION These results indicate a benefit of PBPCs in addition to GM-CSF in alleviating myelosuppression of dose-intensive chemotherapy. Initial collection of PBPCs may allow administration of repetitive cycles of high-dose chemotherapy with acceptable toxicity to outpatients at disease onset.

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.

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