Most Closely Human Leukocyte Antigen (HLA)-Matched Adenovirus-specific T Lymphocytes (Viralym-A)

To make AdV-specific T cells (Viralym-A cells), small pieces of protein called peptides that
come from AdV were mixed with blood cells from healthy donors. These peptides train a kind of
white blood cell called T cells to recognize and kill cells that are infected with AdV. These
T cells were then grown in special growth factors in special flasks in the lab. Once we made
sufficient numbers of cells, we tested them to make sure they recognized cells infected by
adenovirus, and then we froze them.

When we think the subject needs them, Viralym-A cells will be thawed and injected into the
intravenous line. To prevent an allergic reaction, prior to receiving Viralym-A cells the
subject may be given diphenhydramine (Benadryl) and acetaminophen (Tylenol). The subject will
remain in the clinic for at least one hour after the infusion. After the subject receives the
cells, the transplant doctor will monitor the levels of adenovirus in the blood. We will also
take blood to see how long the cells we gave the subject are lasting in the body.

Subjects will continue to be followed by their transplant doctors after the injection. The
subject will either be seen in the clinic or they will be contacted by a research nurse to
follow up for this study every week for 6 weeks, then at 3, 6 and 12 months. The subject may
have other visits for their standard care. Subjects will also have regular blood tests done
to follow their counts and the viral infection as part of their standard care.

To learn more about the way Viralym-A cells are working in the body, an extra 30-40 ml (6-8
teaspoons) of blood will be taken before the infusion and then at study follow-up visits at
1, 2, 3, 4 and 6 weeks, and 3 months after the infusion. Blood should come from the central
intravenous line, and should not require extra needle sticks.

All participants on this study will be infused with the same number (dose) of cells. If
Viralym-A infusion has helped the subjects infection or if they have had a treatment, for
example with steroid drugs that might have destroyed the T cells the subject was given, then
they are allowed to receive up to 4 additional infusions of the Viralym-A cells at the same
initial dose level from 28 days after their initial infusion. Following infusions should be
at least 14 days apart. After each Viralym-A cells infusion, subjects will be monitored as
described above.

Inclusion Criteria:

1. Prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant
using either bone marrow or peripheral blood stem cells or single or double cord blood
within 24 months.

2. Persistent or recurrent adenovirus infection or disease despite at least 7 days of
standard therapy or failure of therapy as described below or if unable to tolerate
standard therapy. Standard therapy is defined as antiviral therapy with cidofovir or
an alternative antiviral agent if patient will not tolerate cidofovir therapy because
of poor renal function.

i. Adenovirus infection: defined as the presence of adenoviral positivity as detected
by polymerase chain reaction (PCR) or culture from ONE site, such as stool or blood or
urine or nasopharynx.

ii. Adenovirus disease: defined as the presence of adenoviral positivity as detected
by PCR, Direct fluorescent assay (DFA) or culture from two or more sites such as stool
or blood or urine or nasopharynx.

iii. Failure of therapy: defined as a rise or a fall of less than 50% in viral load in
peripheral blood or any site of disease as measured by PCR (or any other quantitative
assay) after 7 days of antiviral therapy.

3. Patients with multiple viral infections including AdV are eligible if their AdV
infection is persistent despite standard therapy as defined above. Patients with
multiple infections with one or more reactivation and one or more controlled infection
are eligible to enroll.

4. Clinical status at enrollment to allow tapering of steroids to equal or less than 0.5
mg/kg/day prednisone (or equivalent).

5. Received transplant care locally and will remain in the Houston area for at least 6
weeks post Viralym-A infusion.

6. Hemoglobin (Hgb) > 8.0 (may be transfused).

7. Available Viralym-A T cell line.

8. Negative pregnancy test in female patients if applicable (childbearing potential who
have received a reduced intensity conditioning regimen).

9. Informed consent explained to, understood by and signed by patient/guardian.
Patient/guardian given copy of informed consent.

Exclusion Criteria:

1. Patients receiving Anti-thymocyte globulin (ATG), Campath or other immunosuppressive T
cell monoclonal antibodies within 28 days of treatment with Viralym-A.

2. Patients with other uncontrolled/progressing infections defined as hemodynamic
instability attributable to sepsis or new symptoms, worsening physical signs or
radiographic findings attributable to infection. For bacterial infections, patients
must be receiving definitive therapy and have no signs of progressing infection for 72
hours prior to enrollment. For fungal infections patients must be receiving definitive
systemic anti-fungal therapy and have no signs of progressing infection for 1 week
prior to enrollment. Persisting fever without other signs or symptoms will not be
interpreted as progressing infection.

3. Patients who have received donor lymphocyte infusion (DLI) within 28 days of Viralym-A
infusion.

4. Requirement for FiO2 > 0.5 to maintain arterial oxygen saturation > 90%

5. Endotracheal intubation and mechanical ventilation at any FiO2

6. Hemodynamic instability requiring continuous infusions of inotropes or vasopressors

7. Patients who have received other investigational drugs within 28 days of Viralym-A
infusion.

8. Patients with active acute graft versus host disease (GVHD) grades II-IV.

9. Active and uncontrolled relapse of malignancy.