Haemopoietic cell kinetics in humans treated with rGM-CSF

Int J Cancer. 1992 Jan 2;50(1):26-31. doi: 10.1002/ijc.2910500107.

Abstract

We have investigated the kinetics of myeloid cell proliferation in the marrow of patients with small-cell lung cancer and treated with 10 daily subcutaneous injections of granulocyte/macrophage colony-stimulating factor (GM-CSF). Bone marrow, obtained before and during treatment with the growth factor, was labelled in vitro with tritiated thymidine (3H-TdR). A 3rd bone-marrow sample was obtained 1 hr following an intravenous injection of 3H-TdR. Subsequent daily blood samples were also collected, and 3H-TdR labelling was assessed on these and the marrow preparations by autoradiography. GM-CSF treatment increased the peripheral granulocytic cells nearly 5-fold, but this included significant eosinophilia, so that the neutrophilic granulocytes increased only 3.3-fold. These cells were released from the marrow over a normal time scale, but their peripheral half-life was about 6 times longer than normal and they were probably functionally defective. Furthermore, significant numbers of immature cells were released from the marrow. Neutrophil production stimulated by GM-CSF was thus overestimated by measurement of the apparent peripheral granulocytosis. Increased labelling indices and grain counts in the proliferating granulocytic cells of the marrow indicate shortened cell-cycle times, and the excess granulocyte production appears to be the result of extra amplification divisions in the proliferative compartments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Small Cell / therapy
  • Cell Cycle
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use*
  • Granulocytes / cytology
  • Hematopoiesis / drug effects*
  • Hematopoietic Stem Cells / pathology*
  • Humans
  • Leukocyte Count
  • Male
  • Middle Aged
  • Monocytes / cytology
  • Recombinant Proteins

Substances

  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor