Lung and Bone Marrow Transplantation for Lung and Bone Marrow Failure

The primary purpose of the study is to evaluate the safety and efficacy of performing lung
transplantation followed by cadaveric, partially HLA-matched (≥1/6 HLA-match with an
identical ABO blood type) CD3+/CD19+ depleted bone marrow transplantation in bone marrow
failure and end-stage lung disease. Idiopathic pulmonary fibrosis (IPF) is a chronic,
progressive, and fatal interstitial lung disease for which lung transplantation is the only
therapy shown to prolong survival. Given the association of IPF with hematologic cytopenias
and bone marrow failure, it is proposed that a tandem lung transplantation and bone marrow
transplantation from a single cadaveric donor could be successful. This protocol focuses on
performing combined transplantation for candidates that are unable to undergo standard lung
transplantation. Lung transplantation prior to bone marrow transplantation (BMT) would allow
for restoration of pulmonary function prior to BMT, and to restore hematologic function post
BMT transplantation. The secondary objectives are to evaluate the feasibility and long-term
complications associated with combined solid organ and BMT including the ability to initiate
and successfully withdraw from immunosuppression following BMT and to attain independence
from growth factors, red blood cell or platelet transfusions.

Inclusion Criteria:

Individuals must meet all of the following criteria in order to be eligible for this study.

1. Subject must be able to understand and provide informed consent.

2. Male or female, 18 through 60 years old, inclusive, at the time of informed consent.

3. Meet criteria for UNOS listing for lung transplantation.

4. Patients must have evidence of end stage lung disease. Examples of such diseases
include but are not limited to:

- Pulmonary Fibrosis

- COPD/Emphysema

5. Patients must have evidence of bone marrow failure with abnormal low cell count in at
least one hematopoietic line, making the patient a poor candidate for long-term
immunosuppressive therapy. Eligible patients must meet at least one of the following
criteria:

- Unexplained, non-drug induced neutropenia with absolute neutrophils counts of
<1500/µL the previous year, confirmed by repeat testing

- Unexplained, non-drug induced thrombocytopenia with mean platelets counts of
<100,000/µL the previous year, confirmed by repeat testing

- Unexplained, non-hemolytic anemia, with a hemoglobin level of < 12 g/dL the
previous year, confirmed by repeat testing

6. GFR ≥45 mL/min/1.73 m2.

7. AST, ALT ≤4x upper limit of normal, total bilirubin ≤ 2.5 mg/dL, normal INR, albumin
>3.0 g/dL

8. Cardiac ejection fraction ≥ 40% or shortening fraction ≥26%.

9. Negative pregnancy test for females, unless surgically sterilized.

10. All females of childbearing potential and sexually active males must agree to use a
FDA approved method of birth control for up to 24 months after BMT or for as long as
they are taking any medication that may harm a pregnancy, an unborn child or may cause
birth defect.

11. Subject will also be counseled regarding the potential risks of infertility following
BMT and advised to discuss sperm banking or oocyte harvesting.

Exclusion Criteria:

Individuals who meet any of these criteria are not eligible for this study.

1. Inability or unwillingness of a participant to give written informed consent or comply
with study protocol.

2. Patients who have underlying malignant conditions.

3. HIV positive by serology or PCR, HTLV positive by serology.

4. Females who are pregnant or who are lactating.

5. Allergy to DMSO or any other ingredient used in the manufacturing of the stem cell
product.

6. Uncontrolled infection, as determined by the appropriate imaging and/or confirmatory
testing e.g. blood cultures, PCR testing, etc.

7. Recent recipient of any licensed or investigational live attenuated vaccine(s) within
4 weeks of transplant.

8. Past or current medical problems or findings from physical examination or laboratory
testing that are not listed above, which, in the opinion of the investigator, may pose
additional risks from participation in the study, may interfere with the participant's
ability to comply with study requirements or that may impact the quality or
interpretation of the data obtained from the study.