Photopheresis for the Treatment of Acute Graft Versus Host Disease

ECP uses ultraviolet A radiation to treat lymphocytes. Although the exact reason why ECP may
be beneficial is not completely understood, researchers believe that the lymphocytes treated
this way are less likely to continue causing GVHD.

In this study, researchers want to evaluate whether adding another treatment to standard
therapy with corticosteroids, in this case ECP, will improve the response to therapy,
duration of therapy, and survival. After the diagnosis of acute GVHD, you will be randomly
selected (at the toss of a coin) to be in one of 2 treatment groups. One group will receive
treatment with corticosteroids (like methylprednisolone or prednisone) alone, and the other
will receive ECP treatments in addition to the corticosteroids. ECP treatments are explained
below.

In order to have ECP, you will need a special central venous catheter similar to the one you
have now. A central venous catheter is a sterile flexible tube that will be placed into a
large vein while you are under local anesthesia. Your physician will explain this procedure
to you in more detail, and you will be required to sign a separate consent form for this
procedure.

Blood is drawn by a machine called "photopheresis machine". This blood goes into a bowl
inside the machine, where it is spun and separated into white cells (called buffy coat), red
cells, and platelets. The red cells and platelets are promptly returned to you, while the
white cells in the buffy coat undergo the process of ECP. The buffy coat will come out of the
bowl and will be mixed with a substance called methoxsalen, that will make lymphocytes more
sensitive to the effects of light. After mixing with methoxsalen, the buffy coat goes in to
chamber where it is exposed to ultraviolet A radiation, and from there back to you. This
process is done gradually, in cycles, and takes about 3 hours.

You will have up to 4 of these treatments weekly for the first 14 days of therapy, then 3
treatments weekly from Day 15-28, and after that 2 treatments weekly until Day 60, which is
the end of the study. After Day 60, your doctor will decide whether ECP is worth continuing,
and also the frequency of treatments. It is not necessary to be in the study to continue to
receive ECP treatments. If you respond to the treatment, your corticosteroids will be reduced
slowly to prevent the GVHD from coming back.

The length of corticosteroid therapy will depend on how GVHD responds to the treatment. You
will follow a corticosteroid therapy tapering schedule according to the suggested guidelines.
You will continue to receive tacrolimus or cyclosporine, whichever you have been using as
GVHD prevention, throughout the study independent of what treatment group you are assigned.

While you are getting treatment in this study, every week you will have a physical exam and
blood (about 1 tablespoon) will be drawn for routine tests. If your doctor thinks it is
necessary, blood may be drawn more often.

You will be considered off-study after 6 months of treatment completion. You will be taken
off study if you are unable to comply with study requirements, you refuse to continue
participation in the study, or intolerable side effects occur.

This is an investigational study. ECP has been approved by the FDA for the treatment of a
certain type of lymphomas of the skin and is commercially available. Its use in patients with
GVHD is considered to be investigational. Up to 95 patients will take part in this study. All
will be enrolled at MD Anderson.

Inclusion Criteria:

1. Patients must be recipients of allogeneic bone marrow or stem cell grafts.

2. Patient must weigh above 40 kg

3. Patients must have new onset, clinical grade II-III acute or late-acute GVHD of the GI
tract or liver, or the skin that developed post transplantation. The diagnosis of GVHD
must be pathologically confirmed in at least one organ or highly suspected clinically.
Pathological confirmation may occur after registration and after the start of therapy.
Definition of Late Acute GVHD vs Acute GVHD: The diagnosis of Late Acute GVHD includes
clinical features that are identical to Acute GVHD, however, Late Acute GVHD is
diagnosed on or after day 100 post transplantation.

4. Continued from #3: These manifestations include a maculopapular rash, abnormal liver
studies (cholestatic jaundice) and/or nausea/vomiting / diarrhea. Patients must not
have any concurrent classical features of chronic GVHD in addition to the above
manifestations. Features of chronic GVHD include dry eyes and mouth, contractures,
and/ or sclerodermal, lichenoid skin changes.

5. In the clinical judgment of the PI, patients must be able to sustain a platelet count
and a hematocrit >/= 20,000/mL and >/= 27% respectively, with or without transfusions.

6. The absolute white blood cell count (WBC) must be >1500/mL

7. Patient must be willing to comply with all study procedures.

8. All patients with childbearing potential, including males and females, must commit to
using adequate contraceptive precautions throughout their participation in the study
and for 3 months following the last ECP treatment.

Exclusion Criteria:

1. Patients developing chronic GVHD following immune modulation with immunosuppression
withdrawal or donor lymphocyte infusion (DLI).

2. Any clinical Manifestation consistent with de novo chronic GVHD or overlapped syndrome
of acute and chronic GVHD.

3. Patients who are unable to tolerate the volume shifts associated with ECP treatment
due to the presence of any of the following conditions: uncompensated congestive heart
failure, pulmonary edema, severe asthma or chronic obstructive pulmonary disease,
hepatorenal syndrome.

4. Active bleeding

5. International normalized ration (INR) >2

6. Patients cannot have received methylprednisolone > 2mg/kg/day for more than 72 hours
prior to registration.

7. Patients cannot have received any other immunosuppression for treatment of GVHD but
calcineurin inhibitors and corticosteroids. Patients are allowed to have had any GVHD
prophylaxis with the exception of ECP

8. Patients with known hypersensitivity or allergy to psoralen

9. Patients with known hypersensitivity or allergy to both citrate and heparin

10. Patients with co-existing photosensitive disease (e.g. porphyria, systemic lupus
erythematosus, albinism) or coagulation disorders.

11. Uncontrolled, persistent hypertriglyceridemia, with levels > 800 mg%