Stimulation of myelopoiesis in a patient with congenital neutropenia: Biology and nature of response to recombinant human granulocyte-macrophage colony-stimulating factor

Saroj Vadhan-Raj, Sima S. Jeha, Stephen Buescher, Ann LeMaistre, Garland Yee, Li Lu, Josep Lloreta, William K. Hoots, Walter N. Hittelman, Jordan U. Gutterman, Hal Broxmeyer

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

To stimulate granulopoiesis. we gave recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF; 120 μg/m2/d) to a patient with congenital neutropenia. The treatment resulted in marked increases in white blood cell counts (maximum, 17,400/μL), consisting mainly of eosinophils (maximum, 13,050/μL) and monocytes (maximum, 1305/μL), rather than neutrophils (maximum, 798/ μL). 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.

Original languageEnglish (US)
Pages (from-to)858-864
Number of pages7
JournalBlood
Volume75
Issue number4
StatePublished - Feb 15 1990
Externally publishedYes

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Myelopoiesis
Granulocyte-Macrophage Colony-Stimulating Factor
Eosinophils
Neutrophils
Chemotaxis
Defects
Bone
Therapeutics
Cells
Granulocyte Precursor Cells
Cell Lineage
Phagocytes
Leukocyte Count
Phagocytosis
Cell culture
Granulocytes
Bone Marrow Cells
Agar
Neutropenia, Severe Congenital, Autosomal Recessive 3
Monocytes

ASJC Scopus subject areas

  • Hematology

Cite this

Stimulation of myelopoiesis in a patient with congenital neutropenia : Biology and nature of response to recombinant human granulocyte-macrophage colony-stimulating factor. / Vadhan-Raj, Saroj; Jeha, Sima S.; Buescher, Stephen; LeMaistre, Ann; Yee, Garland; Lu, Li; Lloreta, Josep; Hoots, William K.; Hittelman, Walter N.; Gutterman, Jordan U.; Broxmeyer, Hal.

In: Blood, Vol. 75, No. 4, 15.02.1990, p. 858-864.

Research output: Contribution to journalArticle

Vadhan-Raj, S, Jeha, SS, Buescher, S, LeMaistre, A, Yee, G, Lu, L, Lloreta, J, Hoots, WK, Hittelman, WN, Gutterman, JU & Broxmeyer, H 1990, 'Stimulation of myelopoiesis in a patient with congenital neutropenia: Biology and nature of response to recombinant human granulocyte-macrophage colony-stimulating factor', Blood, vol. 75, no. 4, pp. 858-864.
Vadhan-Raj, Saroj ; Jeha, Sima S. ; Buescher, Stephen ; LeMaistre, Ann ; Yee, Garland ; Lu, Li ; Lloreta, Josep ; Hoots, William K. ; Hittelman, Walter N. ; Gutterman, Jordan U. ; Broxmeyer, Hal. / Stimulation of myelopoiesis in a patient with congenital neutropenia : Biology and nature of response to recombinant human granulocyte-macrophage colony-stimulating factor. In: Blood. 1990 ; Vol. 75, No. 4. pp. 858-864.
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abstract = "To stimulate granulopoiesis. we gave recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF; 120 μg/m2/d) to a patient with congenital neutropenia. The treatment resulted in marked increases in white blood cell counts (maximum, 17,400/μL), consisting mainly of eosinophils (maximum, 13,050/μL) and monocytes (maximum, 1305/μL), rather than neutrophils (maximum, 798/ μL). 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.",
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