Sargramostim for Myeloid Dendritic Cell Deficiency

The overall objective of this project is to study the ability of sargramostim to enhance mDC
level and function, including subsequent stimulation of T cell responses, in various human
subjects with demonstrated myeloid dendritic cell (mDC) and T cell deficiency.

Single center nonrandomized trial with an interrupted time series design involving measures
on blood samples from three separate populations before and after administration of
sargramostim.

The objective is to determine the safety and dose response of sargramostim administration in
healthy participants and in patients with chronic kidney disease (CKD) and kidney
transplants.

Additionally to determine whether reversal of mDC/T cell deficiency by sargramostim results
in augmented T cell responses in these three groups.

Inclusion Criteria:

- Age >18 years < 80 years

- Absence of acute or chronic medical condition and taking no prescription medications
(Project I)

- Stable native or transplant kidney function (Project II/III)

Exclusion Criteria:

- Age < 18 or > 80 years

- History of non-adherence to prescribed medications (Projects II and III)

- Active drug or heavy alcohol use (defined as > 4 drinks/day)

- Pregnancy or breast feeding

- Active infection (bacterial or viral) or clinically significant infections within the
past three months (e.g. those requiring hospitalization, or as judged by the PI,
except for CMV viremia in Project III)

- Active malignancy (with the exception of excised non-metastatic basal cell carcinoma
or squamous cell carcinoma of the skin, or adequately treated pre-invasive cervical
cancer in situ)

- Unstable cardiovascular status (angina, arrhythmias, congestive heart failure (CHF)
etc…)

- History of liver disease (as defined by a diagnosis of uncompensated cirrhosis)

- History of lung disease (including moderate-severe Chronic Obstructive Pulmonary
Disease (COPD), interstitial lung disease, or asthma)

- Known hypersensitivity to yeast-derived products

- Hemoglobin < 10 g/dL and hematocrit < 30%.

- Abnormal white blood cell count (WBC) count at baseline (< 3 or > 12 x 103 cells/mm3,
except Project III)

- Treatment with WBC growth factors (G-CSF or GM-CSF) or immunosuppressive medications
(tacrolimus, cyclosporine, mycophenolate, azathioprine, corticosteroids, chlorambucil,
cyclophosphamide) within 4 weeks of study (erythropoiesis-stimulating agents will be
allowed for Project II and immunosuppression for Project III)

- Treatment with lithium within 4 weeks of study

- History of arterial or venous thrombosis