Stimulation of myelopoiesis in a patient with congenital neutropenia:
biology and nature of response to recombinant human granulocyte- macrophage
colony-stimulating factor
S Vadhan-Raj, SS Jeha, S Buescher, A LeMaistre, G Yee, L Lu, J Lloreta, WK Hoots, WN Hittelman and JU Gutterman
Department of Clinical Immunology and Biological Therapy, University of
Texas M.D., Anderson Cancer Center, Houston 77030.
To stimulate granulopoiesis, we gave recombinant human granulocyte-
macrophage colony-stimulating factor (GM-CSF; 120 microgram/m2/d) to a
patient with congenital neutropenia. The treatment resulted in marked
increases in white blood cell counts (maximum, 17,400/microL), consisting
mainly of eosinophils (maximum, 13,050/microL) and monocytes (maximum,
1305/microL), rather than neutrophils (maximum, 798/microL). Circulating
phagocytes (97% eosinophils) derived after GM-CSF treatment were less
effective in chemotaxis, slower but equally effective in phagocytosis, and
more effective in H2O2 production compared with normal control neutrophils,
but comparable in chemotaxis and H2O2 production to control eosinophils.
Before GM-CSF treatment, the bone marrow showed a maturation defect in the
neutrophilic series that persisted after treatment despite marked increases
in mature cells of other lineages. In vitro agar culture of bone marrow
cells before GM- CSF treatment showed a normal number of granulocyte
colonies; however, maturation was limited to the metamyelocyte stage.
Although the absolute number and cycling rates of myeloid colony forming
cells (predominantly eosinophils) increased after treatment, the maturation
defect in the neutrophilic series persisted. The finding that GM-CSF
induced stimulation of proliferation, which was coupled with maturation in
the eosinophilic and monocytic but not the neutrophilic components,
suggests that this patient had an intrinsic cellular or humoral defect in
neutrophil maturation.
Volume 75,
Issue 4,
pp. 858-864,
02/15/1990
Copyright © 1990 by The American Society of Hematology
