Congenital Agranulocytosis: Prolonged Survival and Terminal Acute Leukemia

Abstract

Three unrelated, Caucasian patients with a disorder resembling infantile genetic agranulocytosis have been studied. There was no history of consanguinity. Parents and siblings were normal. Onset occurred before 3 weeks of age and persisted throughout life. All had severe neutropenia, myeloid arrest pattern of the bone marrow, eosinophilia, monocytosis and hyperglobulinemia. Other congenital anomalies were not present. Their clinical courses were characterized by recurrent, severe bacterial infections particularly of the skin, mouth and lungs but without bacteremia. The infections responded to, but were not prevented by antibiotics, which were administered almost continuously. Fungal infections did not occur and viral infections were not severe. Splenectomy and corticosteroids were without apparent benefit. Relative, though transient, neutrophilia occurred during a few episodes of infection. Chromosome analysis was normal in two of the patients. In one, maturation of neutrophilic leukocytes was not observed in cultures of bone marrow to which normal serum or cysteine was added. One boy is living at 14 10/12 years of age, and one died at 13¾ years of disseminated infection. A unique occurrence was the development of terminal acute leukemia (monocytic) in the third patient, a girl at the age of 14¼ years.

INFANTILE GENETIC AGRANULOCYTOSIS ASSOCIATED WITH CHANGES IN SERUM VITAMIN B12 BINDING PROTEINS

“…The severity of the impairment of granulocyte production is variable, the milder defects carrying a better prognosis. Several cases reports (3,9) include children still alive in the second decade of life, aIthough in one instance death from leukaemia has been noted in these older children (9). The present case illustrates several of the findings described in Kostmann's monograph.…”

“…A high incidence of consanguinity was present in Kostmann's cases and he concluded that the disease was probably caused by an autosomal recessive genetic defect. Subsequent reports have been reviewed by Gilman et al (9) who point out that the mechanism of inheritance was not always similar to that described by Kostmann, since many occur as single cases with no other affected family members. The severity of the impairment of granulocyte production is variable, the milder defects carrying a better prognosis.…”

Severe chronic neutropenia: Treatment and follow‐up of patients in the Severe Chronic Neutropenia International Registry

“…Of greatest interest and concern in this report is the development of leukemia in patients with severe congenital neutropenia. Before the availability of hematopoietic growth factors, it was recognized that leukemic transformation occurred in patients with severe congenital neutropenia [29][30][31][32][33]. Probably most patients with congenital neutropenia died in the first years of life from infections.…”

Neutrophil Marrow Profiles in Patients with Rheumatoid Arthritis and Neutropenia

“…Reduction in segmented marrow cells should be ascribed to accelerated release, a physiological response to a humoral factor associated with neutropenia (Boggs et al, 1968). A true maturation arrest may, nonetheless, be characteristic of acute leukaemia (Elias & Greenberg, 1977) and there is experimental evidence of disordered maturation in some reported cases of neutropenia (Wriedt et al, 1970;Gilman et al, 1970;L'Esperance et al, 1973;Parmley et al, 1975).…”