scholarly journals The effects of daily recombinant human granulocyte colony-stimulating factor administration on normal granulocyte donors undergoing leukapheresis [see comments]

Blood ◽  
1993 ◽  
Vol 81 (7) ◽  
pp. 1883-1888 ◽  
Author(s):  
WI Bensinger ◽  
TH Price ◽  
DC Dale ◽  
FR Appelbaum ◽  
R Clift ◽  
...  
Keyword(s):  
Blood Cells ◽  
Fold Increase ◽  
Not Given ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Normal Individuals ◽  
Red Blood Cell Transfusions ◽  
The Mean ◽  
Circulating Levels ◽  
Stimulating Factor

The effects of daily administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to eight normal volunteers donating granulocytes for neutropenic relatives undergoing marrow transplantation were studied. Granulocyte donors consisted of seven marrow donors (5 syngeneic, 2 HLA identical) and one haploidentical son who had not donated marrow. All donors were administered daily rhG-CSF at a mean dose of 5 micrograms/kg/d (range 3.5 to 6.0) for a mean of 11.75 days (range 9 to 14 days), and granulocytes were collected a mean of 7.6 times (range 4 to 12). RhG-CSF was well tolerated and only minor side effects were observed. All donors became anemic from marrow donation and the removal of red blood cells during the collection procedures. Red blood cell transfusions were not given. All donors had a decrease in platelet counts and the magnitude of the decrement appeared to be greater than in historical donors. This was due in part to increased removal of platelets with the collection product, but a direct effect of rhG-CSF on platelet production cannot be excluded. The mean precollection granulocyte level was 29.6 x 10(9)/L (range 11.8 to 79.8), which was a 10-fold increase over baseline. The mean number of granulocytes collected was 41.6 x 10(9) (range 1.3 to 144.1), which was a six-fold increase over historical donors not receiving rhG-CSF. The mean granulocyte level 24 hours after transfusion into neutropenic recipients was 0.95 x 10(9)/L (median 0.57 and range .06 to 9.47). This study indicates that rhG-CSF is safe to administer to normal individuals, significantly improves the quantity of granulocytes collected, and results in significant circulating levels of granulocytes in neutropenic recipients. Further studies to evaluate rhG- CSF in normal granulocyte donors are warranted.

scholarly journals The effects of daily recombinant human granulocyte colony-stimulating factor administration on normal granulocyte donors undergoing leukapheresis [see comments]

Blood ◽  
1993 ◽  
Vol 81 (7) ◽  
pp. 1883-1888 ◽  
Author(s):  
WI Bensinger ◽  
TH Price ◽  
DC Dale ◽  
FR Appelbaum ◽  
R Clift ◽  
...  
Keyword(s):  
Blood Cells ◽  
Fold Increase ◽  
Not Given ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Normal Individuals ◽  
Red Blood Cell Transfusions ◽  
The Mean ◽  
Circulating Levels ◽  
Stimulating Factor

Abstract The effects of daily administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to eight normal volunteers donating granulocytes for neutropenic relatives undergoing marrow transplantation were studied. Granulocyte donors consisted of seven marrow donors (5 syngeneic, 2 HLA identical) and one haploidentical son who had not donated marrow. All donors were administered daily rhG-CSF at a mean dose of 5 micrograms/kg/d (range 3.5 to 6.0) for a mean of 11.75 days (range 9 to 14 days), and granulocytes were collected a mean of 7.6 times (range 4 to 12). RhG-CSF was well tolerated and only minor side effects were observed. All donors became anemic from marrow donation and the removal of red blood cells during the collection procedures. Red blood cell transfusions were not given. All donors had a decrease in platelet counts and the magnitude of the decrement appeared to be greater than in historical donors. This was due in part to increased removal of platelets with the collection product, but a direct effect of rhG-CSF on platelet production cannot be excluded. The mean precollection granulocyte level was 29.6 x 10(9)/L (range 11.8 to 79.8), which was a 10-fold increase over baseline. The mean number of granulocytes collected was 41.6 x 10(9) (range 1.3 to 144.1), which was a six-fold increase over historical donors not receiving rhG-CSF. The mean granulocyte level 24 hours after transfusion into neutropenic recipients was 0.95 x 10(9)/L (median 0.57 and range .06 to 9.47). This study indicates that rhG-CSF is safe to administer to normal individuals, significantly improves the quantity of granulocytes collected, and results in significant circulating levels of granulocytes in neutropenic recipients. Further studies to evaluate rhG- CSF in normal granulocyte donors are warranted.

5-Androstene-3b,17b-Diol Administration of Mice Exposed to Total Body Irradiation Results in Rapid Reconstitution of Immature Bone Marrow Progenitor Cells and Synergizes with Thrombopoietin but Not with Granulocyte-Colony Stimulating Factor.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2327-2327
Author(s):  
Fatima SF Aerts Kaya ◽  
Trudi P Visser ◽  
James M Frincke ◽  
Dwight R. Stickney ◽  
Chris L Reading ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Total Body Irradiation ◽  
Blood Cells ◽  
Fold Increase ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Total Body ◽  
Marrow Cellularity ◽  
Immature Cells ◽  
Stimulating Factor

Abstract 5-AED (5-androstene-3β,17β-diol) is a naturally occurring adrenal cortical steroid, which displays radioprotective effects in both rodents and non-human primates, resulting in accelerated multilineage hematopoiesis and enhanced survival after total body irradiation (TBI), including a 1-log accelerated CD34+ cell reconstitution in bone marrow of non-human primates. Pegylated granulocyte-colony stimulating factor (Peg-G-CSF) is known to stimulate lineage-specific recovery of neutrophils, whereas the effects of thrombopoietin (TPO) are broader and include protection of short-term spleen repopulating immature cells as well as platelet recovery. To gain insight into the mechanism of 5-AED on immature hematopoietic cells, the effects of 5-AED on multilineage hematopoiesis and recovery of specific repopulating stem and progenitor cell subsets after TBI was evaluated in combination with and relative to either Peg-G-CSF or TPO. For direct measurements of the radioprotective effect of 5-AED, BALB/c mice were exposed to a midlethal dose of 6 Gy TBI. Two hours after TBI, mice were injected IM with 40 mg/kg 5-AED or the carrier, with or without 0.225 mg TPO or 10 mg Peg-G-CSF IP. Radioprotective effects of 5-AED on immature repopulating cell subsets were assessed by exposing BALB/c donor mice to 3 fractions of 2 Gy TBI, separated by 24 hours, and treatment with 40 mg/kg/d 5-AED or the carrier IM, or 0.7 mg TPO IP after each fraction or a single injection of 10 mg Peg-G-CSF IP after the first fraction. Twenty four hours after the last fraction, bone marrow of donor mice was examined for immature cell content per femur using the marrow repopulating ability (MRA day 13) assay and the CFU-S day 12 after transplantation in 8 Gy irradiated mice. After 6 Gy TBI, BALB/c mice treated with 5-AED displayed an accelerated multilineage recovery with increased white blood cells (p<0.001), blood platelets (p<0.0001) and red blood cells (p<0.03), as well as increased bone marrow cellularity (p<0.0001) and elevated numbers of bone marrow colony forming cells (p<0.00001) at 14 days post-TBI in comparison to placebo-treated animals. Increasing the 5-AED dose up to 200 mg/kg did not augment this effect. Combined treatment with 5-AED and Peg-G-CSF or TPO treatment did not result in an additive effect in this setting. However, after the fractionated 3x2 Gy, a 5- and 7- fold increase in CFU-S relative to radiation controls was observed in the 5-AED and TPO groups, respectively, and a synergistic 20-fold increase in CFU-S day 12 was observed when 5-AED and TPO were used simultaneously. Consistent with earlier observations, Peg-GCSF alone did not affect CFU-S day 12 and appeared to dampen the effect of 5-AED. MRA, expressed as GM-CFU per femur at 13 days after transplantation, was found to be increased 5- to 6-fold with 1002 colonies (range 0-5785) for 5-AED versus 174 (5-360) for radiation controls. This is in contrast to TPO, which promotes CFU-S reconstitution at the expense of the more immature MRA (Neelis et al. 1998: Blood92, 1586). Thus, 5-AED as a single agent stimulates multilineage hematopoiesis and increases bone marrow cellularity following TBI. This effect is mediated by increased survival and/or reconstitution of immature repopulating cells in a pattern distinct from that of TPO. Consistently, 5-AED strongly synergizes with TPO at the level of immature cells from which reconstitution originates, thus revealing a novel mechanism of bone marrow protection in cytoreductive therapy.

scholarly journals Quantitative and cell-cycle differences in progenitor cells mobilized by recombinant human interleukin-7 and recombinant human granulocyte colony-stimulating factor

Blood ◽  
1996 ◽  
Vol 88 (11) ◽  
pp. 4139-4148 ◽  
Author(s):  
KJ Grzegorzewski ◽  
KL Komschlies ◽  
JL Franco ◽  
FW Ruscetti ◽  
JR Keller ◽  
...  
Keyword(s):  
Stem Cells ◽  
Progenitor Cells ◽  
Combined Treatment ◽  
Fold Increase ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Interleukin 7 ◽  
Stimulating Factor

Abstract Administration of recombinant human interleukin-7 (rhIL-7) to mice increases the exportation of myeloid progenitors (colony-forming unit [CFU]-c and CFU-granulocyte erythroid megakaryocyte macrophage [CFU-GEMM]) from the bone marrow (BM) to peripheral organs, including blood, and also increases the number of primitive progenitor and stem cells in the peripheral blood (PB). We now report that combined treatment of mice with rhIL-7 and recombinant human granulocyte-colony stimulating factor (rhG-CSF) stimulates a twofold to 10-fold increase in the total number of PB CFU-c, and a twofold to fivefold increase in the total number of PB CFU-spleen at day 8 (CFU-S8) over the increase stimulated by rhIL-7 or rhG-CSF alone. In addition, the quality of mobilized cells with trilineage, long-term marrow-repopulating activity is maintained or increased in mice treated with rhIL-7 and rhG-CSF compared with rhIL-7 or rhG-CSF alone. These differences in mobilizing efficiency suggest qualitative differences in the mechanisms by which rhIL-7 and rhG-CSF mobilize progenitor cells, in fact, the functional status of progenitor cells mobilized by rhIL-7 differs from that of cells mobilized by rhG-CSF in that the incidence of actively cycling (S-phase) progenitors obtained from the PB is about 20-fold higher for rhIL-7-treated mice than for mice treated with rhG-CSF. These results suggest the use of rhIL-7-mobilized progenitor/stem cells for gene-modification and tracking studies, and highlight different functions and rates of repopulation after reconstitution with PB leukocytes obtained from mice treated with rhIL-7 versus rhG-CSF.

scholarly journals Synergistic effects of thrombopoietin and granulocyte colony- stimulating factor on neutrophil recovery in myelosuppressed mice

Blood ◽  
1996 ◽  
Vol 88 (9) ◽  
pp. 3363-3370 ◽  
Author(s):  
A Grossmann ◽  
J Lenox ◽  
TA Deisher ◽  
HP Ren ◽  
JM Humes ◽  
...  
Keyword(s):  
Blood Cells ◽  
Synergistic Effects ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Spleen Cells ◽  
Hematopoietic System ◽  
Neutrophil Recovery ◽  
Chemotherapy Dose ◽  
Complete Blood Counts ◽  
Stimulating Factor

Severe suppression of the hematopoietic system is a major factor in limiting chemotherapy dose escalation. To determine whether a combination of human recombinant granulocyte colony-stimulating factor (G-CSF) and thrombopoietin (TPO) would alter recovery of platelets, red blood cells (RBCs), or neutrophils after myeloablative therapy, myelosuppressed mice were treated with sc injections of TPO (90 micrograms/kg), G-CSF (250 micrograms/kg). TPO plus G-CSF or vehicle and complete blood counts were measured. Marrow and spleen cells were obtained at various times and assayed for erythroid, myeloid, and megakaryocytic progenitors. The prolonged neutropenia in vehicle controls (14 days) was significantly shortened in mice treated with G-CSF or TPO for 14 days. The combination of TPO plus G-CSF further reduced the duration of neutropenia. TPO and TPO plus G-CSF treatments also significantly shortened thrombocytopenia compared to vehicle. Recovery of RBCs was also enhanced in mice treated with either G-CSF or TPO, or the combination. Furthermore, treatment with G-CSF and/or TPO hastened myeloid, erythroid, and megakaryocyte progenitor recovery compared to vehicle controls. These results show that the combination of TPO plus G-CSF acts synergistically to accelerate neutrophil recovery in myelosuppressed mice and does not compromise the platelet or RBC response to TPO therapy.

scholarly journals Hematopoietic progenitors in cyclic neutropenia: effect of granulocyte colony-stimulating factor in vivo

Blood ◽  
1990 ◽  
Vol 75 (10) ◽  
pp. 1951-1959 ◽  
Author(s):  
AR Migliaccio ◽  
G Migliaccio ◽  
DC Dale ◽  
WP Hammond
Keyword(s):  
Growth Factor ◽  
Progenitor Cells ◽  
Blood Cells ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Cyclic Neutropenia ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Stimulating Factor

Abstract The number and growth factor requirements of committed progenitor cells (colony-forming units-granulocyte/macrophage and burst-forming units- erythroid) in three patients with cyclic neutropenia (two congenital, one acquired) were studied before and during therapy with recombinant human granulocyte colony-stimulating factor (G-CSF; 3 to 10 micrograms/kg/d). When the patients with congenital disease were treated with G-CSF, the cycling of blood cells persisted, but the cycle length was shortened from 21 days to 14 days, and the amplitude of variations in blood counts increased. There was a parallel shortening of the cycle and increase of the amplitude of variations (from two- to three-fold to 10- to 100-fold) in the number of both types of circulating progenitor cells in these two patients. In the patient with acquired cyclic neutropenia, cycling of both blood cells and progenitors could not be seen. In cultures deprived of fetal bovine serum, erythroid and myeloid bone marrow progenitor cells from untreated patients and from normals differed in growth factor responsiveness. As examples, maximal growth of granulocyte/macrophage (GM) colonies was induced by granulocyte/macrophage (GM)-CSF plus G-CSF in the patients, whereas a combination of GM-CSF, G-CSF and interleukin- 3 (IL-3) was required in the normals, and erythropoietin alone induced fourfold more erythroid bursts from cyclic neutropenic patients than from normal donors (46% versus 11% of the maximal colony number, respectively). The growth factor responsiveness of marrow progenitor cells slightly changed during the treatment toward the values observed with normal progenitors. These results indicate that treatment with G- CSF not only ameliorated the neutropenia, but also increased the amplitude and the frequency of oscillation of circulating progenitor cell numbers. These data are consistent with the hypothesis that G-CSF therapy affects the proliferation of the hematopoietic stem cell.

Dose-intensification of MVAC with recombinant granulocyte colony-stimulating factor as initial therapy in advanced urothelial cancer.

1993 ◽  
Vol 11 (3) ◽  
pp. 408-414 ◽  
Author(s):  
A D Seidman ◽  
H I Scher ◽  
J L Gabrilove ◽  
D F Bajorin ◽  
R J Motzer ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Transitional Cell ◽  
Dose Intensity ◽  
Fold Increase ◽  
Dose Schedule ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Dose Intensification ◽  
Stimulating Factor ◽  
Delivered Dose

PURPOSE This study was undertaken to define an escalated dose schedule of methotrexate, vinblastine, doxorubicin, and cisplatin (E-MVAC) with hematopoietic growth-factor support, to define the ability to deliver E-MVAC with recombinant human granulocyte colony-stimulating factor (rhG-CSF) on 21- and 14-day schedules, and to assess the ability of rhG-CSF to maintain dose-intensity over four cycles of chemotherapy. PATIENTS AND METHODS Twenty-three patients with transitional-cell carcinoma of the urothelium received E-MVAC in a phase I investigation. Patients were treated on an every-21-day (n = 19) or every-14-day schedule of administration (n = 4), with rhG-CSF support. Delivered dose-intensity was calculated at the completion of four cycles of therapy relative to the planned administration of conventional MVAC (relative dose-intensity [RDI]). Peripheral-blood progenitor cell kinetics in these patients were studied prospectively. RESULTS Overall, the delivered RDI was 33% higher than the previously reported delivered dose-intensity of MVAC without hematopoietic support (140% for doxorubicin, 51% for cisplatin). Dose-intensity was well maintained through three cycles of therapy, after which leukopenia and thrombocytopenia became dose-limiting. Sixty-nine percent of patients with measurable disease responded, four (25%) with complete remissions. In five patients treated beyond the maximally tolerated dose (MTD), a 50- to 200-fold increase in G-CSF, granulocyte-macrophage CSF (GM-CSF), and interleukin-3 (IL-3)-responsive peripheral-blood progenitor cells over baseline was observed after 9 days of rhG-CSF administration. CONCLUSION These findings demonstrate the feasibility and limitations of dose intensification of M-VAC with rhG-CSF. While the overall impact of the increased drug administration can only be assessed in randomized comparisons, the results of the present trial suggest that escalations of the components of the four-drug regimen are unlikely to improve significantly the outcome for patients with advanced urothelial tract tumors.

Effect of leukocyte compatibility on neutrophil increment after transfusion of granulocyte colony-stimulating factor–mobilized prophylactic granulocyte transfusions and on clinical outcomes after stem cell transplantation

Blood ◽  
2000 ◽  
Vol 95 (11) ◽  
pp. 3605-3612 ◽  
Author(s):  
Douglas R. Adkins ◽  
Lawrence T. Goodnough ◽  
Shalini Shenoy ◽  
Randy Brown ◽  
Jennifer Moellering ◽  
...  
Keyword(s):  
Stem Cell ◽  
Clinical Outcomes ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Granulocyte Transfusion ◽  
Screening Assay ◽  
Cell Dose ◽  
Component Cell ◽  
The Mean ◽  
Stimulating Factor

The primary limitations of granulocyte transfusions include low component cell dose and leukocyte incompatibility. Component cell dose improved with granulocyte colony-stimulating factor (G-CSF) mobilization, and the transfusion of G-CSF–mobilized, human leukocyte antigen (HLA)-matched granulocyte components resulted in significant, sustained absolute neutrophil count (ANC) increments. However, the effect of leukocyte compatibility on outcomes with G-CSF–mobilized granulocyte transfusions is unclear. The objectives were to determine the effect of leukocyte compatibility on ANC increments and selected clinical outcomes after transfusion of prophylactic, G-CSF–mobilized granulocyte components into neutropenic recipients of autologous peripheral blood stem cell (PBSC) transplants. Beginning on transplant day 2, 23 evaluable recipients were scheduled to receive 4 alternate-day transfusions of granulocyte components apheresed from a single donor given G-CSF. G-CSF was also given to recipients after transplantation. Recipient ANC was determined before and sequentially after each granulocyte transfusion to determine the peak ANC increment. Leukocyte compatibility was determined at study entry only by a lymphocytotoxicity screening assay (s-LCA) against a panel of HLA-defined cells. Eight recipients had positive s-LCA. On days 2 and 4, the mean peak ANC increments after granulocyte transfusion were comparable between the cohorts with positive and negative s-LCA. However, the mean peak ANC increments on day 6 (246/μL vs 724/μL; P = .05) and day 8 (283/μL vs 1079/μL; P = .06) were lower in the cohort with positive s-LCA, in spite of the transfusion of comparable component cell doses. Adverse reactions occurred with only 5 of 87 (5.7%) granulocyte transfusions and were not associated with leukocyte compatibility test results. Platelet increments, determined 1 hour after granulocyte transfusion, were comparable between the cohorts. Although the 2 cohorts received PBSC components with similar CD34+ cell doses, the cohort with a positive s-LCA had delayed neutrophil engraftment and a greater number of febrile days and required more days of intravenous antibiotics and platelet transfusions. Leukocyte incompatibility adversely affected ANC increments after the transfusion of G-CSF–mobilized granulocyte components and clinical outcomes after PBSC transplantation.

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