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

Abstract

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.

Granulocyte and Granulocyte-Macrophage Colony-Stimulating Factors in Cord and Maternal Serum at Delivery

“…Cord blood: linear associations potential use of exogenous G-CSF or GM-CSF in the management of neonatal sepsis. Experience with the use of these factors in children and adults has indicated that G-CSF is well tolerated, is associated with few side effects, and can produce an improvement in neutrophil counts and a reduction in the number and severity of infections (8,(48)(49)(50)(51)(52). In contrast.…”

Recommendations on hematopoietic stem cell transplantation for inherited bone marrow failure syndromes

“…The use of G-CSF therapy has radically changed patient outcomes. 26 HSCT is still the only curative treatment for patients refractory to G-CSF and in cases of clonal evolution (AML and MDS).…”

An acquired G-CSF receptor mutation results in increased proliferation of CMML cells from a patient with severe congenital neutropenia

“…1,2 Recombinant human granulocyte colony-stimulating factor (rh-G-CSF) has revolutionized the care of individuals with CN; it acts by stimulating neutrophil production and thereby reduces the incidence and severity of infections. 3,4 Data from the International Registry for Severe Chronic Neutropenia (SCNIR) revealed that CN is a preleukemic disorder, with an estimated 15% risk of transformation to myelodysplastic syndrome (MDS) and acute leukemia. 5 While most CN patients have developed MDS or acute myeloid leukemia (AML) in the context of prior rh-G-CSF treatment, few cases of AML were described in the pre-G-CSF era.…”