In vitro and in vivo Effects of Recombinant Human Erythropoietin on Human Hemopoietic Progenitor Cells

Ganser, Arnold; Bergmann, Martin; Völkers, B.; Grützmacher, P.; Hoelzer, Dieter

doi:10.1159/000416010

Cited by 11 publications

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“…4,10,14 Erythropoietin has been shown in vitro to significantly increase numbers of BFU-E and CFU-GEMM in patients with anemia of chronic renal failure. 16 In man rhEpo alone for mobilization did not produce the same effects in a cohort of untreated lymphoma patients or in patients with different cancers. 17,23 Recently, two non-randomized retrospective studies were published indicating a superior effect of the addition of rhEpo to rhG-CSF compared to rhG-CSF alone for PBPC mobilization.…”

Section: Discussionmentioning

confidence: 91%

“…4,[8][9][10][11][12][13][14][15] Erythropoietin (rhEpo) has previously been shown to have effects in vivo on circulating PBPC and to increase peripheral blood colony-forming cell numbers but not of cells capable of long-term hematopoiesis. 16,17 Recently, there have been two non-randomized studies indicating an advantage for PBPC mobilization of the combination of rhEpo and rhG-CSF over rhG-CSF alone. 18,19 In order to further address this question we initiated a prospective randomized trial in patients with newly diagnosed stage II-IV breast cancer.…”

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confidence: 99%

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Mobilization of peripheral blood progenitor cells in patients with breast cancer: a prospective randomized trial comparing rhG-CSF with the combination of rhG-CSF plus rhEpo after VIP-E chemotherapy

Waller¹,

Lintig²,

Daskalakis³

et al. 1999

Bone Marrow Transplant

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Summary:Peripheral blood progenitor cells (PBPC) can be mobilized by chemotherapy, cytokines, or the combination of both. Recently, data from two non-randomized studies were published, showing an advantage for a combination of rhG-CSF plus rhEpo compared to rhG-CSF alone in mobilization of PBPC. To address this question we initiated a prospective, randomized trial in patients with breast cancer. Thirty (28 female, two male) of 32 randomized patients were evaluable. After primary surgery, therapy consisted of two cycles of VIP-E chemotherapy followed by high-dose (HD) chemotherapy with VIC. Mobilization and harvest of PBPC followed cycle 2. Group A received 5 g rhG-CSF/kg body weight (bw) plus 150 IU rhEpo/kg bw. Group B was treated with 5 g rhG-CSF/kg bw from d1 until end of harvest. In the peripheral blood CD34 + cells as well as colony-forming units (CFU) started to rise on d8 with a peak on d10, followed by a decrease. No significant differences were observed between the groups. Furthermore, there was no significant difference with regard to MNC, CD34 + cells BFU-E and CFU-GM in apheresis products. Transplantation of Ͼ1 × 10 6 CD34 + cells/kg bw after HD chemotherapy resulted in normal hematological recovery of all patients. No differences were observed in time to neutrophil or platelet recovery and need for blood product support. In this study addition of rhEpo to our standard mobilization chemotherapy did not result in improved mobilization of PBPC or in clinical benefits after HD chemotherapy. Keywords: PBPC mobilization; cytokines; erythropoietin; rhG-CSF; breast cancer Bone marrow toxicity has been the limiting factor for doseintensity of chemotherapy in the past. High-dose (HD) chemotherapy with subsequent transplantation of autologous hematopoietic progenitor cells has offered a new therapeutic modality to increase dose-intensity compared to stan-

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Section: Discussionmentioning

confidence: 91%

mentioning

confidence: 99%

Mobilization of peripheral blood progenitor cells in patients with breast cancer: a prospective randomized trial comparing rhG-CSF with the combination of rhG-CSF plus rhEpo after VIP-E chemotherapy

Waller¹,

Lintig²,

Daskalakis³

et al. 1999

Bone Marrow Transplant

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“…Ganser et al [14] and Geissler et al [15] both reported an increase of BFU-E and CFU-GEMM after onset of treatment. Whereas Geissler et al also observed an increase of CFU-GM incidence within one week of supplementation therapy, Ganser et al reported the incidence of CFU-GM to not be significantly altered.…”

Section: Discussionmentioning

confidence: 97%

“…In vivo effects of rHuEPO on circulating human hemopoietic progenitor cells have been reported for adults with anemia of chronic renal failure treated with far lower dosages (40 and 120 U/kg/week) [14,15]. Ganser et al [14] and Geissler et al [15] both reported an increase of BFU-E and CFU-GEMM after onset of treatment.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Recombinant Human Erythropoietin on Circulating Hematopoietic Progenitor Cells in Anemic Premature Infants

et al. 1997

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In vitro and animal studies suggest that high concentrations of recombinant human erythropoietin (rHuEPO) might divert multipotent progenitors into erythroid maturation at the expense of granulocyte production. We determined whether changes of number and lineage commitment of peripheral blood progenitor cells occur in premature infants during therapy with rHuEPO. Thirty preterm infants were randomly assigned either to receive 300 IU of eopoetin alpha s.c. per kilogram body weight three times a week for four weeks or to a control group. At study entry and after two weeks of treatment the numbers of circulating BFU-E, granulocyte-macrophage colonyforming units (CFU-GM) and granulocyte-erythrocytemacrophage-megakaryocyte CFU (CFU-GEMM) were analyzed by semisolid culture technique, CD34 + cells and early myeloid CD34 + CD45RA -progenitors by flow cytometry. As compared with the control group, rHuEPO treatment did not exert any significant modulatory effect on numbers of CFU-GM, nor was there a significant change in numbers of BFU-E, CFU-GEMM, total-CFU, percentage of CD34 + or CD34 + CD45RA -cells. Mean neutrophil count was not significantly reduced at any period during the study. Compared with the control group, the infants receiving rHuEPO had higher hematocrit values (p = 0.003) and absolute reticulocyte counts (p < 0.001). The median cumulative volume of blood transfused per kilogram per day was 0.86 ml (first quartile 0.5 ml; third quartile 1.1 ml) in the control group and 0 ml (first quartile 0 ml; third quartile 0.47 ml) in the rHuEPO group (p = 0.038). We conclude using a relatively high dose of rHuEPO in premature infants, no significant in vivo effect on circulating peripheral blood progenitor or neutrophil count could be detected. Stem

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“…Erythropoietin given at a dose between 40 and 120 U/kg 3 times a week increases the number of circulating burstforming unit erythrocyte (BFU-E) and CFU-GEMM, but not of CFU-GM in patients with anemia or chronic renal failure [38]. Erythropoietin at a dose of 300 U/kg per day yields in a 3-fold higher number of circulating CFU-GM, BFU-E and CD34+ cells [39].…”

Section: Erythropoietinmentioning

confidence: 99%

Steady-State Mobilization of Peripheral Blood Progenitor Cells by Cytokines Alone in Patients with Solid Tumors or Hematological Malignancies

Kröger¹,

Zeller²,

Hassan³

et al. 1999

Transfus Med Hemother

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Cytokines are involved in hematopoiesis and cell growth regulation. Many cytokines have the property of increasing the number of hematopoietic progenitor cells circulating in peripheral blood. Since it has been shown that peripheral blood progenitor support after myeloablative therapy resulted in a faster engraftment than after autologous bone marrow support, recent effort is focusing on optimizing stem cell harvest by different cytokines, cytokine combination, or evaluation of dose and schedule dependencies. One of the first cytokines shown to mobilize stem cells within peripheral blood was the granulocyte-stimulating factor (G-CSF). This review is focusing on the current state of cytokine-induced mobilization of stem cells in patients with hematological malignancies or solid tumors.

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In vitro and in vivo Effects of Recombinant Human Erythropoietin on Human Hemopoietic Progenitor Cells

Cited by 11 publications

References 0 publications

Mobilization of peripheral blood progenitor cells in patients with breast cancer: a prospective randomized trial comparing rhG-CSF with the combination of rhG-CSF plus rhEpo after VIP-E chemotherapy

Mobilization of peripheral blood progenitor cells in patients with breast cancer: a prospective randomized trial comparing rhG-CSF with the combination of rhG-CSF plus rhEpo after VIP-E chemotherapy

The Effect of Recombinant Human Erythropoietin on Circulating Hematopoietic Progenitor Cells in Anemic Premature Infants

Steady-State Mobilization of Peripheral Blood Progenitor Cells by Cytokines Alone in Patients with Solid Tumors or Hematological Malignancies

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