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Apheresis and CD34+ Selection of Mobilized Peripheral Blood CD34+ Cells From Patients With DOCK8 Deficiency, LAD-1, and GATA2 Deficiency

15 Years
40 Years
Open (Enrolling)

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Trial Information

Apheresis and CD34+ Selection of Mobilized Peripheral Blood CD34+ Cells From Patients With DOCK8 Deficiency, LAD-1, and GATA2 Deficiency


Primary immunodeficiency diseases (PID) represent candidate genetic disorders for new
therapeutic approaches. Our laboratory is developing gene therapy for patients with PID
using autologous CD34+ hematopoietic stem cells (HSC). Gene therapy may circumvent problems
with allogeneic HSC transplantation, especially graft rejection and
graft-versus-host-disease. We are particularly interested in three PID: Dedicator of
CytoKinesis-8 (DOCK8) deficiency, Leukocyte Adhesion Deficiency type 1 (LAD-1), and GATA2
Deficiency. For DOCK8 deficiency, and LAD-1, the disease gene has been cloned. The genetic
basis for MonoMAC has now been determined to be due to mutations in GATA2.. Testing new
vector constructs and transduction conditions for gene therapy would be considerably
enhanced by the acquisition of peripheral blood CD34+ cells from patients with these
immunodeficiency diseases.


To provide a source of granulocyte colony stimulating factor (G-CSF) mobilized peripheral
blood CD34+ hematopoietic stem cells (HSC) for laboratory research studies including
optimization of vector and transduction conditions for gene therapy for DOCK8 deficiency,
LAD-1, and MonoMAC.


Patients 15-40 years old with DOCK8 deficiency, LAD-1, and MonoMAC who meet the eligibility
requirements will be considered for this protocol.


Patients 15-40 years old with DOCK8 deficiency, LAD-1, and MonoMAC will receive five days of
G-CSF followed by a single apheresis. CD34+ cell will be selected and frozen in aliquots by
the Cell Processing Section of the Department of Transfusion Medicine. No treatments, or
investigational therapy will be administered on this protocol.

Inclusion Criteria


1. Patient age of 15-40 years.

2. Diagnosis of DOCK8 deficiency, LAD-1, or MonoMAC:

DOCK8 Deficiency

Homozygous or compound heterozygous mutations in the DOCK8 gene.


Less than 10% CD18 expression on the neutrophil surface.

GATA2 Deficiency

1. Onset of immunodeficiency disease beyond infancy.

2. Clinical history of at least two episodes of life-threatening infection with
opportunistic organisms.

3. Mutation of GATA2 Gene

c) Serum creatinine < 1.5 mg/dL.

d) Total Bilirubin < 3mg/dl, ALT and AST < 5 times upper limit of normal.

e) Ability to give informed consent.

f) Adequate venous access for peripheral apheresis, or consent to use a temporary
central venous catheter for apheresis.

g) Female patients of childbearing age must have a negative urine pregnancy test
within one week of beginning G-CSF administration.

h) A patient who is lactating must be willing and able to interrupt breast-feeding or
substitute formula feeding for her infant during the period of filgrastim
administration and for two days following the final dose. Filgrastim may be secreted
in human milk, although its bioavailability from this source is not known. Limited
clinical data suggest that short-term administration of filgrastim or sargramostim to
neonates is not associated with adverse outcomes

j) Potential patients must be screened by an apheresis nurse to check venous access
before protocol entry. Antecubital veins must be adequate for peripheral access
during leukapheresis, or the patient must give written consent for placement of a
temporary central venous access catheter.


1. HIV infection.

2. Chronic hepatitis B or hepatitis C virus infection.

3. History of psychiatric disorder which may compromise compliance with protocol,
or which does not allow for appropriate informed consent.

4. Active infection that is not responding to antimicrobial therapy.

f) Pregnant. The effects on breast-milk are also unknown and may be harmful to the
infant; therefore, women should not breast feed during the interval from study entry
to collection.

g) Sexually active individuals capable of becoming pregnant who are unable or
unwilling to use effective form(s) of contraception during time enrolled on study.
Effective forms of contraception include one or more of the following: intrauterine
device (IUD), hormonal (birth control pills, injections, or implants), tubal
ligation/hysterectomy, partner's vasectomy, barrier methods, (condom, diaphragm, or
cervical cap), or abstinence. Males on the protocol must use an effective form of
contraception at study entry.

h) Presence of active malignancy in another organ system other than the hematopoietic

i) History of hypertension that is not controlled by medication, stroke, or severe
heart disease. Individuals with symptomatic angina will be considered to have severe
heart disease and will not be eligible.

j) Other medical contraindications to stem cell donation (i.e. severe
atherosclerosis, autoimmune disease, iritis or episcleritis, deep venous thrombosis,
cerebrovascular accident)

k) Thrombocytopenia (platelets less than 50,000 per microL) at baseline evaluation.

l) Patients receiving experimental therapy or investigational agents.

m) Sensitivity to filgrastim or to E. coli-derived recombinant protein products.

n) Patients must test negative for transfusion-transmissible infectious agents,
including hepatitis B (HBsAg), hepatitis C (anti-HCV), HIV (anti-HIV-1/2).

Type of Study:


Study Design:

Time Perspective: Prospective

Principal Investigator

Dennis D Hickstein, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Federal Government

Study ID:




Start Date:

August 2010

Completion Date:

Related Keywords:

  • LAD-1
  • DOCK8
  • MonoMAC
  • Immunodeficiency
  • DOCK8
  • LAD-1
  • MonoMAC
  • Immunologic Deficiency Syndromes



National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892