Natural History Study for BEN
| Status: | Recruiting |
|---|---|
| Conditions: | Blood Cancer, Hematology |
| Therapuetic Areas: | Hematology, Oncology |
| Healthy: | No |
| Age Range: | 5 - Any |
| Updated: | 3/24/2019 |
| Start Date: | June 3, 2003 |
| Contact: | Matthew M Hsieh, M.D. |
| Email: | matthewhs@mail.nih.gov |
| Phone: | (301) 402-7687 |
Natural History and Molecular Characterization of Benign Ethnic Neutropenia in Individuals of African Descent
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. identify individuals of African descent with BEN.
2. determine the effects of two drugs, G-CSF and dexamethasone, on granulocyte production
and movement.
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.
Study participants will be asked to interview with the research team, undergo physical exams,
donate a blood sample, and receive G-CSF by injection, followed by dexamethasone (orally)
about three weeks later. They also will be required to undergo apheresis three times, a
procedure in which blood is drawn from a donor and separated into its components. Some
components are retained for research analyses, such as granulocytes, and small amount of
blood; the remainder is returned by transfusion to the donor. This procedure will be required
of participants before they receive G-CSF, the day after they receive G-CSF, and the day
after they receive dexamethasone. Gene messages (mRNA will be isolated from granulocytes, and
analyzed to better understand granulocyte growth and movement.
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. identify individuals of African descent with BEN.
2. determine the effects of two drugs, G-CSF and dexamethasone, on granulocyte production
and movement.
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.
Study participants will be asked to interview with the research team, undergo physical exams,
donate a blood sample, and receive G-CSF by injection, followed by dexamethasone (orally)
about three weeks later. They also will be required to undergo apheresis three times, a
procedure in which blood is drawn from a donor and separated into its components. Some
components are retained for research analyses, such as granulocytes, and small amount of
blood; the remainder is returned by transfusion to the donor. This procedure will be required
of participants before they receive G-CSF, the day after they receive G-CSF, and the day
after they receive dexamethasone. Gene messages (mRNA will be isolated from granulocytes, and
analyzed to better understand granulocyte growth and movement.
Benign ethnic neutropenia (BEN) is defined by peripheral blood absolute neutrophil count less
than 1.5 x 10 (9) per liter without an increase in infections. This condition has been
described in individuals of African descent. Although these individuals have normal myeloid
maturation on bone marrow examinations, they appear to release fewer neutrophils into the
circulation when stimulated by hydrocortisone, compared to normal controls. This suggests
that there may be differences in the regulation of neutrophil release or trafficking. In the
past decade, granulocyte-colony stimulating factor (G-CSF) has been widely used in a variety
of clinical settings, from patients with chemotherapy-induced neutropenia to normal
volunteers for peripheral blood stem cell collection. G-CSF, however, has not been used in
individuals with BEN. Furthermore, gene expression in neutrophil proliferation and
trafficking has not been studied in these individuals. The purpose of this study are to (1)
identify individuals with BEN; (2) follow the natural history of BEN; (3) determine if there
is a familial inheritance pattern; (4) characterize and compare neutrophil response to
dexamethasone and G-CSF; (5) compare the pattern of neutrophil gene expression by microarray
analyses; and (6) determine if mutations are present at the DNA level to account for gene
expression pattern differences in individuals of African descent with and without BEN at
baseline, post dexamethasone, and post G-CSF stimulation.
than 1.5 x 10 (9) per liter without an increase in infections. This condition has been
described in individuals of African descent. Although these individuals have normal myeloid
maturation on bone marrow examinations, they appear to release fewer neutrophils into the
circulation when stimulated by hydrocortisone, compared to normal controls. This suggests
that there may be differences in the regulation of neutrophil release or trafficking. In the
past decade, granulocyte-colony stimulating factor (G-CSF) has been widely used in a variety
of clinical settings, from patients with chemotherapy-induced neutropenia to normal
volunteers for peripheral blood stem cell collection. G-CSF, however, has not been used in
individuals with BEN. Furthermore, gene expression in neutrophil proliferation and
trafficking has not been studied in these individuals. The purpose of this study are to (1)
identify individuals with BEN; (2) follow the natural history of BEN; (3) determine if there
is a familial inheritance pattern; (4) characterize and compare neutrophil response to
dexamethasone and G-CSF; (5) compare the pattern of neutrophil gene expression by microarray
analyses; and (6) determine if mutations are present at the DNA level to account for gene
expression pattern differences in individuals of African descent with and without BEN at
baseline, post dexamethasone, and post G-CSF stimulation.
- INCLUSION CRITERIA:
- 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
(Bullet)1,500/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, in
the last 6 months, with granulocytes <1,500/mm3, platelet >150,000/mm3, hemoglobin
>12.5g/dL, and normal MCV
- 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
EXCLUSION CRITERIA:
- 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
4.2.4
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
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Phone: 800-411-1222
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