OBJECTIVES: I. Document the clinical course of severe chronic neutropenia (SCN).

II. Monitor and assess long term safety of primary treatment in SCN patients in the United States, Canada, Europe, and Australia.

III. Study the incidence and outcome of adverse events such as osteoporosis, splenomegaly, cytogenetic abnormalities, myelodysplastic syndrome, and leukemia.

IV. Evaluate growth and development and hematologic parameters. V. Monitor for clinically significant changes in primary treatment response over time.

VI. Establish a physician network to increase the understanding of SCN. VII. Establish a demographic database to allow for future research.

PROTOCOL OUTLINE:

Patients are treated by the referring physician as medically indicated. Clinical data are collected at baseline and then every 6 months.

Inclusion Criteria - Subjects are eligible for enrollment if they meet the following criteria:

1. A confirmed diagnosis of severe chronic neutropenia based on documented absolute neutrophil counts of less than 0.5x109/L on at least three occasions in the three months prior to enrollment.

2. For subjects with presumed cyclic neutropenia, documentation of at least two neutrophil cycles is preferred. Documentation should include the nadirs with neutrophil counts of less than 200 followed by a clear increase in the counts generally to at least 500 to 1000 followed by a second nadir, usually expected to occur at about three weeks after the first nadir, i.e., cycling with a three week periodicity. Documentation with at least six weeks of counts and two expected nadirs is preferred.

   Cases not showing clear oscillations will be categorized as congenital (if neutropenia or neutropenic complications appear to have occurred from birth) or idiopathic (if all symptoms in evidence point to an acquired disorder occurring after the first year of life).

3. Bone marrow aspiration consistent with the diagnosis of congenital, cyclic or idiopathic neutropenia. In all of these conditions, it is expected that the marrow aspirate evaluation at the time of neutropenia will show a deficiency of mature neutrophils. An exception is myelokathexis, a condition with large accumulations of neutrophils with pycnotic nuclei in the marrow. Bone marrow aspirates may show some dyspoiesis of the neutrophil lineage, but abnormalities of erythropoiesis or platelet formation are, in general, inconsistent with the diagnosis of SCN.

4. Normal cytogenetic evaluation. The only exception being cases of well documented severe congenital neutropenia with preferably previously documented normal cytogenetic evaluation will now be enrolled in the Registry at the time of evolution to leukemia.

5. History of recurrent infections (i.e., severe mouth ulcers, gingivitis and sinusitis).

6. Age greater than three months.

7. Independent of hematological parameters, subjects with the following diagnoses may be included: Shwachman-Diamond syndrome (SDS), glycogen storage disease type 1b (GSD1b), Barth syndrome, and Cohen's syndrome.

8. Subjects with moderately severe chronic neutropenia (i.e., ANC less than 1.0x109/L) and recurrent severe infections (i.e., deep tissue infections of subcutaneous areas, lungs, liver, etc.).

9. Immune neutropenia with positive anti-neutrophil antibodies meeting criteria in 1, 3, 5 and 6.

10. All SCN subjects originally enrolled in Amgen-sponsored SCN studies.

Exclusion Criteria

1. Neutropenia known to be drug induced
2. Primary myelodysplasia
3. Primary leukemia
4. Aplastic anemia
5. Known HIV disease
6. Systemic autoimmune diseases such as rheumatoid arthritis or systemic lupus erythematosus
7. Chemotherapy-induced neutropenia (within the last 5 years)

patients diagnosed with severe chronic neutropenia