Safety and Efficacy Study of Photopheresis With UVADEX to Prevent Graft-versus-Host Disease

Approximately 30% of HLA-identical related bone marrow graft recipients and up to 90% of
patients receiving bone marrow from unrelated donors develop significant acute GvHD despite
the use of prophylactic therapies such as cyclosporine and methotrexate. About half of these
patients respond to initial treatment with steroids and require no further treatment. The
remainder of these patients are either unresponsive to initial therapy or become
steroid-resistant over time. The prognosis in these cases is poor and mortality for patients
with steroid-resistant GvHD may be as high as 50%.

ECP is a technique in which peripheral white blood cells are exposed to a photoactivatable
compound (UVADEX) administered extracorporeally and ultraviolet A light. After cells are
reinfused into the patient, their function is altered, thereby activating mechanisms that
allow for further regulation of specific lymphocyte populations. ECP has shown activity in
several inflammatory and autoimmune diseases, including scleroderma, rheumatoid arthritis,
transplantation rejection, acute and chronic GvHD.

In a previous single-center, open label, single-arm study of 56 patients receiving ECP
treatment on two consecutive days and reduced-intensity bone-marrow conditioning prior to
bone marrow transplantation from matched or partially matched human donors, the incidence of
grade II-IV acute GvHD was less than 10%. This is in contrast to an expected incidence of
approximately 40%.

The purpose of this study is to determine the role of ECP, administered pre-transplant, in
preventing GvHD when used in conjunction with a standard myeloablative conditioning regimen.

Inclusion Criteria:

- Patients with a diagnosis of a malignancy of the blood (e.g. leukemia) for which
allogeneic bone marrow or peripheral blood stem cell transplantation is a treatment
option.

- Patients who are candidates for a standard allogenic bone marrow transplant or PBSC
transplant.

- Patients must have adequate renal, hepatic, pulmonary and cardiac function to enable
the patient to tolerate shifts in the volumes of body fluids associated with
extracorporeal photopheresis, as determined by the physician's clinical judgement.

- Patients must weigh at least 40 kg (88 lbs)

Exclusion Criteria:

- Patients who have received a prior bone marrow transplant or peripheral blood stem
cell transplant.