Severe Chronic Neutropenia International Registry
Clinical Trial Information
Trial Contact: El-Shami, Jessica; Francois, Laetitia Claire; Leffin, Melissa; Spinelli, Jennifer
IRB No: 10.013.01
Protocol Abbrev: Neutropenia Registry
Principal Investigator: Vincent F. Giusti, MD
Sub Investigators: Eslin, Don MD; Smith, Amy MD; Sutphin, Robert MD; Levy, Alejandro MD
Age Group: Pediatric
Secondary Protocol No: Neutropenia Registry
Applicable Disease Sites: Neutropenia
ClinicalTrials.gov ID: NCT00004342
The original objectives were to document the clinical course of severe chronic neutropenia and develop a database on the safety and efficacy of long-term treatment with G-CSF and other therapies. Additional goals were to establish a physician network to increase the understanding of SCN.
The Registry has successfully developed its database on efficacy and safety of treatment of SCN, and its resources have been extremely valuable for defining the genetic, molecular and cellular basis for cyclic and various causes of neutropenia. The current objectives of the Registry are:
1. Document the clinical course of SCN subjects and their responses to therapy.
2. Determine the incidence and outcome of various clinical events associated with SCN and its treatment including: a. osteoporosis; b. vasculitis; c. glomerulonephritis; d. splenomegaly/hepatomegaly; e. cytogenetic abnormalities; f. myelodysplastic syndrome; g. leukemia.
3. Evaluate the outcome for pregnancies in SCN subjects, including subjects receiving various therapies for their neutropenia.
4. Evaluate the effectiveness of hematopoietic transplantation as a treatment for SCN.
5. Serve as a comprehensive information resource for the education of physicians, subjects and families interested in SCN.
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
10. All SCN subjects originally enrolled in Amgen-sponsored SCN studies.