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Hematopoietic recovery following high-dose combined alkylating-agent chemotherapy and autologous bone marrow support in patients in phase-I clinical trials of colony-stimulating factors: G-CSF, GM-CSF, IL-1, IL-2, M-CSF.

Publication ,  Journal Article
Laughlin, MJ; Kirkpatrick, G; Sabiston, N; Peters, W; Kurtzberg, J
Published in: Ann Hematol
December 1993

Hematopoietic recovery in 115 patients with metastatic breast cancer or metastatic melanoma, enrolled in phase-I studies of recombinant growth factors while undergoing treatment with high-dose chemotherapy with autologous bone marrow support, was examined with assays of bone marrow progenitor cells and peripheral blood progenitor cells, and by evaluation of peripheral blood counts. Groups of patients receiving hematopoietic cytokine support [with interleukin-1 (IL-1), interleukin-2 (IL-2), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), or monocyte CSF (M-CSF)] post marrow infusion were compared with contemporaneous control patients not receiving growth factor support. Patients receiving GM-CSF demonstrated statistically significant increases in the growth of granulocyte/macrophage colony-forming units (CFU-GM) in the bone marrow and peripheral blood compared with control patients. The effect of GM-CSF was dose dependent in the early period post marrow infusion (day +6) with bone marrow CFU-GM colonies at doses 8-16 micrograms/kg/day 34 times those measured in controls. Significant increases in bone marrow multipotential progenitor cells (CFU-GEMM) were seen in patients receiving GM-CSF day +21 post marrow infusion. Patients receiving IL-1 demonstrated significant increases in bone marrow CFU-GM at day +21, maximal at dosages of 24-32 ng/kg/day. There were no significant increases in burst forming unit-erythroid (BFU-E) among any study group. Patients receiving G-CSF had significantly increased absolute neutrophil counts (ANC) and total white blood cell counts (WBC) by day +11 post transplant compared with control patients. Patients receiving GM-CSF demonstrated significantly increased WBC (greater than 2000/mm3) at day +11 and ANC greater than 500/mm3 at day +16. Optimal dose of G-CSF and GM-CSF to stimulate neutrophil recovery post transplant was 4-8 micrograms/kg/day and 8-16 micrograms/kg/day, respectively. Platelet recovery did not differ among the six study groups. These data demonstrate accelerated myeloid recovery after high-dose chemotherapy and autologous bone marrow support in patients receiving either G-CSF or GM-CSF. Moreover, GM-CSF and IL-1 stimulate myelopoiesis at the level of bone marrow CFU-GM, while G-CSF causes earlier neutrophil recovery peripherally.

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Published In

Ann Hematol

DOI

ISSN

0939-5555

Publication Date

December 1993

Volume

67

Issue

6

Start / End Page

267 / 276

Location

Germany

Related Subject Headings

  • Transplantation, Autologous
  • Time Factors
  • Recombinant Proteins
  • Platelet Count
  • Melanoma
  • Macrophage Colony-Stimulating Factor
  • Leukocyte Count
  • Interleukin-2
  • Interleukin-1
  • Immunology
 

Citation

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Laughlin, M. J., Kirkpatrick, G., Sabiston, N., Peters, W., & Kurtzberg, J. (1993). Hematopoietic recovery following high-dose combined alkylating-agent chemotherapy and autologous bone marrow support in patients in phase-I clinical trials of colony-stimulating factors: G-CSF, GM-CSF, IL-1, IL-2, M-CSF. Ann Hematol, 67(6), 267–276. https://doi.org/10.1007/BF01696346
Laughlin, M. J., G. Kirkpatrick, N. Sabiston, W. Peters, and J. Kurtzberg. “Hematopoietic recovery following high-dose combined alkylating-agent chemotherapy and autologous bone marrow support in patients in phase-I clinical trials of colony-stimulating factors: G-CSF, GM-CSF, IL-1, IL-2, M-CSF.Ann Hematol 67, no. 6 (December 1993): 267–76. https://doi.org/10.1007/BF01696346.
Journal cover image

Published In

Ann Hematol

DOI

ISSN

0939-5555

Publication Date

December 1993

Volume

67

Issue

6

Start / End Page

267 / 276

Location

Germany

Related Subject Headings

  • Transplantation, Autologous
  • Time Factors
  • Recombinant Proteins
  • Platelet Count
  • Melanoma
  • Macrophage Colony-Stimulating Factor
  • Leukocyte Count
  • Interleukin-2
  • Interleukin-1
  • Immunology