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

Inclusion Criteria

- 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.

LAD-1

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.

EXCLUSION CRITERIA:

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
system.

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).