Kostmann Disease Follow-up

Updated: Aug 24, 2017
  • Author: Peter N Huynh, MD; Chief Editor: Harumi Jyonouchi, MD  more...
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Follow-up

Further Outpatient Care

Obtain a CBC count with differential twice per week during the first 4 weeks after the initiation of granulocyte-colony stimulating factor (G-CSF) or for 2 weeks following any dosage adjustments. Thereafter, obtain a CBC count with differential monthly for 6 months. When the minimum daily dose is found, the maintenance phase can be started, with monitoring of absolute neutrophil counts every 3-6 months.

Routine clinical follow-up every 3 months for patients who are stable is recommended.

Enroll patients in the Severe Chronic Neutropenia International Registry (SCNIR).

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Further Inpatient Care

Patients admitted for inpatient care related to infection warrant blood, urine, and infectious-site cultures, as well as chest radiography, as clinically indicated. Aggressive intravenous antibiotic therapy and appropriate supportive therapies should be initiated. Consultation with pediatric immunologist, pediatric hematologist, and infectious diseases specialist is recommended.

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Transfer

Once severe congenital neutropenia is suspected, patient should be referred to a specialized treatment center regarding genetic testing and treatment.

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Deterrence/Prevention

Provide genetic counseling to parents of infants because Kostmann disease has an autosomal recessive form of inheritance. Other disorders of severe congenital neutropenia demonstrate several modes of inheritance, including autosomal recessive, autosomal dominant, sporadic, and X-linked forms.

Maintaining an adequate absolute neutrophil count (≥1000/μL) with G-CSF is central to preventing infections.

Annual bone marrow examination for morphology and cytogenetic testing should be performed in order to identify any changes indicating malignant transformation and to allow for early intervention with bone marrow transplantation.

Regular G-CSF receptor analysis should be performed to identify mutations. This can be done on either peripheral blood or bone marrow samples by laboratories headed by the SCNIR.

Regular dental and periodontal evaluation and care should be performed in order to minimize dental complications. The characteristic gingivitis and periodontal disease persist even after G-CSF.

Isolating patients within their homes or away from crowds has shown little practical value.

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Complications

Most complications relate to infections. [27]

Bone demineralization occurs in approximately 50% of patients, which may result in bone pain and unusual fractures, either as a part of the pathophysiology of the disease or potentially from either endogenous or exogenous G-CSFs by increased bone resorption.

About 1 in 5 patients with severe congenital neutropenia develop secondary malignancies. The incidence of acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) in severe congenital neutropenia after 10 years of G-CSF treatment is 21%. Acquired mutations in G-CSF receptor CSF3R are a highly predictive marker for the progression of severe congenital neutropenia to leukemia. [14] Of patients with severe congenital neutropenia, 20-30% have acquired mutations in the CSF3R gene, which produce C-terminally truncated hyperresponsive forms of the G-CSFRhyper and a strong predisposition for MDS and AML.

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Prognosis

In the 1950s, almost all patients would die of sepsis, cellulitis, or pneumonia within the first 2 years of life. In the 1960s and 1970s, more antibiotic therapy was used and lethal infections were less frequent.

In the 1970s, survival with severe congenital neutropenia started to improve owing to antibiotic prophylaxis and to curative parenteral antimicrobial chemotherapy.

Since 1987, the use of G-CSF has resulted in fewer infections of shorter duration. This has dramatically improved patient's quality of life and prolongs survival. However, G-CSF and neutrophil recovery does not improve chronic stomatitis or gingivitis, and tooth loss can occur.

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Patient Education

Educate patients and their families on the signs and symptoms of infections to ensure appropriate and prompt therapy.

Inform patients and their families of the risk for developing leukemia.

The Immune Deficiency Foundation is an important resource for education and support for patients and families with any primary immunodeficiency disease. The telephone number is 1-800-296-4433. The Web site is www.primaryimmune.org. The foundation's mailing address is 40 W Chesapeake Ave, Suite 308, Towson, MD 21204; some states have local chapters.

The Jeffrey Modell Foundation, at 747 3rd Avenue, New York, NY 10017, also provides educational support. The telephone number is 1-866-INFO-4-PI. The Web site is www.jmfworld.org.

The SCNIR was established in March 1994, in the United States, Australia, Canada, and the European Community. The SCNIR is directed by a scientific advisory board of physicians from around the world who care for severe congenital neutropenia patients. Their mission is to establish a worldwide database of treatment and disease-related outcomes for persons diagnosed with severe chronic neutropenia. Collection of this information will lead to improved medical care and is used for research to determine the causes of neutropenia. The Web site is www.depts.washington.edu/registry.

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