Natural History Study for BEN

NCT00059423 | Completed

• 2 other identifiers: 03016803-H-0168
• Study Type: observational
• Target: 178
• Locations: 1 country
• Sites: 1

Brief Summary

In recent decades, hematologists have noticed that persons of African descent sometimes have lower white blood cell counts of a certain type, called granulocytes. These cells help to fight infections. The lower number of granulocytes in this situation does not appear to lead to more infections, and these individuals do not have any symptoms. This condition is called benign ethnic neutropenia (BEN), and is observed in a small percentage of individuals of African descent. This study will investigate the condition by studying people with and without BEN. The goals of this study are to:

1. 1.identify individuals of African descent with BEN.
2. 2.determine the effects of two drugs, G-CSF and dexamethasone, on granulocyte production and movement.
3. 3.determine whether there are differences in those with and without BEN in the way genes are stimulated after the administration of G-CSF and dexamethasone.

Conditions

Neutropenia; Agranulocytosis; Hematologic Diseases; Leukocyte Disorders; Leukopenia

Keywords

Leukapheresis; G-CSF; Dexamethasone; mRNA; Benign Ethnic Neutropenia; BEN; Healthy Volunteer; HV

Outcome Measures

Primary Outcomes (1)

• Serial blood counts in BEN

  In our study, we hope to further elucidate the etiology of BEN in research subjects by isolating granulocyte mRNA after G-CSF and dexamethasone stimulation, applying microarray analyses to screen for gene expression differences, and confirming expression pattern differences by DNA analyses. We will focus on genes that are important in the proliferation and trafficking of neutrophils,such as PRV-1, elastase, myeloblastin, transcription factor PU.1, CAAT enhancing binding protein-alpha (C /EBP), stromal derived factor-1 (SDF-1), and CXC receptor-4 (CXCR4).

  Ongoing

Study Arms (2)

1

Individuals of African descent with benign ethnic neutropenia (BEN) at baseline

2

Individuals of African descent without benign ethnic neutropenia (BEN) at baseline

Eligibility Criteria

• Age: 5 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Since BEN is a condition of individuals of African descent, volunteer recruitment will be focused in this ethnic population. Accrual for BEN subjects will be based on entry criteria, and not on gender or age (in those 5 years or greater). The minimum age is 5 years because these older children would have larger veins and would be more likely to cooperate with blood draws. Subjects without BEN will be selected to match age and gender of BEN subjects to minimize the differential effects of age and gender to the responses to G-CSF and dexamethasone and in microarray analyses.

You may qualify if:

• Individuals of African descent of age 5 or greater
• Normal renal function: creatinine \<1.5 mg/dL and proteinuria \<1+
• Normal liver function: bilirubin \<1.5 mg/dL and transaminases within normal limits
• For control subjects: WBC within normal range (3,300-9,600/mm3), granulocytes/neutrophils greater than or equal to 2,000/mm3, platelets \>150,000/mm3, hemoglobin \> 11.5g/dL and normal MCV
• For benign ethnic neutropenic subjects: two blood counts, at least 1 month apart, with granulocytes/neutrophils \<1,500/mm3, platelet \>150,000/mm3, hemoglobin \>12.5g/dL, and normal MCV. We will also follow subjects whose neutrophil counts are between 1500 and 2000/mm3 in a separate cohort periodically (e.g. once every 1-2 years) to see if their blood counts behave more like BEN or normal subjects.
• Female volunteers of childbearing age should not be pregnant
• Meets NIH Department of Transfusion Medicine (DTM) eligibility criteria for blood component donation for in vitro research uses (negative serologic tests for syphilis, hepatitis B and C, HIV, and HTLV-1)
• Ability to give informed consent to participate in the protocol

You may not qualify if:

• Any underlying hematologic disorder including anemia, and sickle cell disease. Subjects with thalassemia or sickle cell trait are not excluded.
• Current use of corticosteroids, e.g. prednisone, dexamethasone, or hydrocortisone. Corticosteroids must be discontinued at least one month prior
• Active or chronic viral, bacterial, fungal, or parasitic infection. Any antibiotic use should be discontinued at least one month prior
• History of autoimmune disease, such as rheumatoid arthritis or systemic lupus erythematosus, or positive anti-nuclear antibody (ANA ELISA) of 3 E.U. (ELISA units) or greater.
• Low B12 or folate levels, or abnormal thyroid function tests
• History of cancer or chemotherapy, except squamous carcinoma of the skin and cervical carcinoma in situ
• Pregnant woman or positive urine pregnancy test
• History of clinically significant cardiovascular disease (cardiology consultation may be obtained when clinically indicated)
• Any positive serum screening test as listed below
• Allergy to G-CSF or bacterial E. coli products
• Active pulmonary disease or a pulse-ox level of less than 95% on screening exam

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Ash RC, Mendelsohn LA, Marshall ME. Hemopoietic marrow function in chronic neutropenia of blacks: cure of aplastic anemia by allogeneic marrow transplantation from a neutropenic sibling donor. Am J Hematol. 1986 Jun;22(2):205-12. doi: 10.1002/ajh.2830220212.

  PMID: 3518419 BACKGROUND

• Haddy TB, Rana SR, Castro O. Benign ethnic neutropenia: what is a normal absolute neutrophil count? J Lab Clin Med. 1999 Jan;133(1):15-22. doi: 10.1053/lc.1999.v133.a94931.

  PMID: 10385477 BACKGROUND

• Mason BA, Lessin L, Schechter GP. Marrow granulocyte reserves in black Americans. Hydrocortisone-induced granulocytosis in the "benign" neutropenia of the black. Am J Med. 1979 Aug;67(2):201-5. doi: 10.1016/0002-9343(79)90391-7.

  PMID: 463924 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Neutropenia; Agranulocytosis; Hematologic Diseases; Leukocyte Disorders; Leukopenia

Condition Hierarchy (Ancestors)

Cytopenia; Hemic and Lymphatic Diseases

Study Officials

• Matthew M Hsieh, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2003
• First Posted: April 25, 2003
• Study Start: June 3, 2003
• Primary Completion: April 23, 2019
• Study Completion: June 26, 2020
• Last Updated: March 22, 2024

Record last verified: 2020-06

Locations

US (1)