Congenital Neutropenia: Advances in Diagnosis and Treatment.
Congenital Neutropenia: Advances in Diagnosis and Treatment.
Purpose of Review: A decade after the availability of hematopoietic growth factors, the long-term outcome of severe congenital neutropenia has dramatically changed. The prolonged survival of neutropenic patients receiving hematopoietic growth factors has drawn attention to the heterogeneity of this disease and to the complications of treatment. The dose of granulocyte colony stimulating factor that is required to obtain normal levels of circulating neutrophils and to prevent fever and infections is quite variable among patients, but is higher in children with severe congenital neutropenia than in those with other conditions of neutropenia. Moreover, leukemic transformation during treatment is not observed in all patients, but is more typical of severe congenital neutropenia and Shwachman-Diamond patients.
Recent Findings: In recent years, the converging efforts of hematologists, immunologists and geneticists have led to the discovery of the genetic and biochemical basis of severe congenital neutropenia; cyclic neutropenia; warts, hypogammaglobulinemia, immunodeficiency, myelokathexis or WHIM syndrome and other rarer conditions associated to neutropenia.
Summary: Although the diagnosis of congenital neutropenia includes many disorders of distinct origin and variable prognosis, their treatment is still based on granulocyte colony stimulating factor administration. Understanding the pathogenesis of these forms of neutropenia and their evolution will focus future studies on the mechanisms of normal and pathological myelopoiesis and on the development of the most appropriate treatment for each type of neutropenia.
Severe neutropenia constitutes a heterogeneous group of genetic and acquired hematopoietic disorders that are characterized by a reduction of the absolute neutrophil counts (ANCs) that persist for several months and predispose patients to bacterial infections, including deep tissue infections, sepsis, and fever. There is a great degree of variability in the lower limit of neutrophil blood counts that is both age- and race-dependent because normal levels are lower in infants (1×10/l) than in older children and adults (1.5×10/l) and in black than in Caucasian peoples. However, recurrent bacterial infections are not frequently observed until ANCs fall below the limit of severe neutropenia (cells <0.5×10/l). Even patients with the same number of blood circulating neutrophils may display various degrees of susceptibility to bacterial infections because the causative mechanism influences the clinical outcome of the disease. As a matter of fact, disorders of myelopoiesis such as severe chronic neutropenia (SCN) are characterized by a larger number and severity of infectious episodes than acquired neutropenia types such as autoimmune neutropenia, which usually lacks major sepsis episodes.
Purpose of Review: A decade after the availability of hematopoietic growth factors, the long-term outcome of severe congenital neutropenia has dramatically changed. The prolonged survival of neutropenic patients receiving hematopoietic growth factors has drawn attention to the heterogeneity of this disease and to the complications of treatment. The dose of granulocyte colony stimulating factor that is required to obtain normal levels of circulating neutrophils and to prevent fever and infections is quite variable among patients, but is higher in children with severe congenital neutropenia than in those with other conditions of neutropenia. Moreover, leukemic transformation during treatment is not observed in all patients, but is more typical of severe congenital neutropenia and Shwachman-Diamond patients.
Recent Findings: In recent years, the converging efforts of hematologists, immunologists and geneticists have led to the discovery of the genetic and biochemical basis of severe congenital neutropenia; cyclic neutropenia; warts, hypogammaglobulinemia, immunodeficiency, myelokathexis or WHIM syndrome and other rarer conditions associated to neutropenia.
Summary: Although the diagnosis of congenital neutropenia includes many disorders of distinct origin and variable prognosis, their treatment is still based on granulocyte colony stimulating factor administration. Understanding the pathogenesis of these forms of neutropenia and their evolution will focus future studies on the mechanisms of normal and pathological myelopoiesis and on the development of the most appropriate treatment for each type of neutropenia.
Severe neutropenia constitutes a heterogeneous group of genetic and acquired hematopoietic disorders that are characterized by a reduction of the absolute neutrophil counts (ANCs) that persist for several months and predispose patients to bacterial infections, including deep tissue infections, sepsis, and fever. There is a great degree of variability in the lower limit of neutrophil blood counts that is both age- and race-dependent because normal levels are lower in infants (1×10/l) than in older children and adults (1.5×10/l) and in black than in Caucasian peoples. However, recurrent bacterial infections are not frequently observed until ANCs fall below the limit of severe neutropenia (cells <0.5×10/l). Even patients with the same number of blood circulating neutrophils may display various degrees of susceptibility to bacterial infections because the causative mechanism influences the clinical outcome of the disease. As a matter of fact, disorders of myelopoiesis such as severe chronic neutropenia (SCN) are characterized by a larger number and severity of infectious episodes than acquired neutropenia types such as autoimmune neutropenia, which usually lacks major sepsis episodes.
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