Mary Ann Bonilla

Effects of Recombinant Human Granulocyte Colony-Stimulating Factor on Neutropenia in Patients with Congenital Agranulocytosis

Congenital agranulocytosis is a disorder characterized by severe neutropenia and a profound deficiency of identifiable neutrophil progenitors in bone marrow. In an attempt to stimulate neutrophil production and thereby reduce the morbidity and mortality associated with this disease, we administered recombinant human granulocyte colony-stimulating factor (rhG-CSF) in doses of 3 to 60 micrograms per kilogram of body weight per day to five patients with congenital agranulocytosis. In all five patients, an increase in the number of neutrophils was noted eight to nine days after the initiation of the effective dosage (the dose at which the neutrophil count reached 1000 cells per microliter or more and the bone marrow showed granulocyte maturation beyond the myelocyte stage). The absolute neutrophil counts rose from less than 100 to between 1300 and 9500 cells per microliter. Marrow aspirates obtained after 14 days at the effective dosage showed maturation to the mature neutrophil stage. The side effects that were observed were medullary pain, splenomegaly, and an elevation of levels of leukocyte alkaline phosphatase. All five patients have had sustained neutrophil counts of 1000 cells per microliter or more for 9 to 13 months while receiving subcutaneous maintenance therapy. Preexisting chronic infections have resolved clinically, and the number of new infectious episodes and the requirement for intravenous antibiotics have decreased. We conclude that treatment with rhG-CSF can lead to a large increase in the numbers of functional neutrophils in patients with congenital agranulocytosis.

Effects of Human Granulocyte Colony-Stimulating Factor in a Patient with Idiopathic Neutropenia

CHRONIC idiopathic neutropenia is characterized by maturational arrest of neutrophil precursors in the bone marrow and a circulating neutrophil count of less than 1500 cells per microliter. Other h...

Colony-Stimulating Factors in Leukopoiesis

Normal hematopoiesis entails a constant equilibrium. It aims to maintain a given number of red cells, white cells, and platelets and adjusts to the body’s requirement for these cells in response to different stimuli such as infection, trauma, or stress. The basic pluripotent stem cell is capable of giving rise to committed progenitor cells, which in turn differentiate into the mature blood cells. This pluripotent stem cell is capable of self- renewal, whereas the committed progenitor cell is not. In humans hematopoiesis occurs in the bone marrow, whereas in the mouse it occurs both in the bone marrow and in the spleen.