• INCLUSION CRITERIA:

To be eligible, patients must have passed the same screening criteria as for the main protocol but with more stringent platelet level requirements:

Signed and dated consent form for main protocol and substudy protocol must be obtained prior to conducting any study procedure.

Patients must be greater than or equal to 18 years of age.

Patients must weight greater than or equal to 40 kg (88 lb).

Patients must have had Crohn's disease for at least 6 months' duration, with ileitis, colitis, or ileocolitis confirmed by radiography or endoscopy.

Patients must have a CDAI greater than or equal to 220 to less than 450.

Patients must have a CRP greater than 10.0 mg/L or evidence of active inflammatory luminal Crohn's disease as demonstrated by superficial and/or ulcerations, pseudopolys, and/or ulcerated stnosis on colonoscopy within 8 weeks of screening.

Patients taking steroids must be on a prednisone equivalent less than 25 mg/d or an oral budesonide dose less than 9 mg/d.

Concomitant medications may include:

• any stable dose of aminosalicylates, antibiotics, or immunosuppressants (6-MP, AZA, or MTX, e.g.) for at least 4 weeks.
• corticosteroids or p.o. budesonide for at least 2 weeks.
• anti-TNF agents (infliximab or adalimumab) for at least 8 weeks.

Patients must have a history of failed response or intolerance to treatment with immunosuppressants or anti-TNF agents. A failed response is the persistence of active Crohn's symptoms despite prior or current treatment with at least one of the following:

Azathioprine 2-3 mg/kg for 12 weeks;

6-MP 1.0-1.5 mg/kg/d for 12 weeks;

Methotrexate 25 mg/wk for 8 weeks;

Infliximab greater than or equal to 5 mg/kg for 4 weeks (i.e. at least one infusion);

Adalimumab greater than or equal to 40 mg SC for 4 weeks (i.e. at least two injections);

Intolerance to immunosuppressants or anti-TNF agents is experiencing side effects related to at least one of the agents listed above at Grade 2 or higher according to the Common Toxicity Criteria that limit or proscribe their use at doses needed to adequately control the activity of the patients' Crohn's disease.

Patients discontinuing therapies prior to enrolling must have done so by the following times:

• Antibiotics, aminosalicylates, corticosteroids or PO budesonide for at least 2 weeks.
• Immunosuppressants or anti-TNF agents for at least 8 weeks.
• Other investigational agents or non-biologics for at least 4 weeks and other biologics for at least 8 weeks.

Patients may have fistulae are permitted, provided: patients have predominantly luminal Crohn's disease and fistulae are not associated with abscess formation.

Patients must have a platelet count greater than or equal to 50,000/micro L.

Female patients must be: postmenopausal, surgically incapable of bearing children, or practicing an acceptable method of birth control (acceptable methods include hormonal contraceptives, intrauterine devices, spermicide and barrier). Abstinence or partner/spouse sterility may also qualify at the Investigator's discretion. If female patients is of child-bearing potential, she must have a negative urine pregnancy test at screening. Male patients must also commit to using adequate contraceptive precautions (condoms). All patients must commit to using adequate contraceptive precautions throughout their participation in the study and for at least 3 months following their last ECP treatment.

Patients must be able and willing to comply with all main protocol and study procedures.

EXCLUSION CRITERIA:

The presence of any of the following criteria will prohibit patients from study participation:

Patients who are concomitantly using biologic agents other than anti-TNF agents; cyclosporine, tacrolimus, mycophenylate mofetil, or investigational Crohn's therapies.

Patients who, in the opinion of the Investigator may not be able to remain on a stable dose of concomitant Crohn's disease medication during the 12- week Treatment Period.

Patients with currently symptomatic untreated diarrhea, due to conditions other than inflammatory Crohn's disease (e.g. bacterial or parasitic gastroenteritis, bile salt diarrhea, or bacterial overgrowth).

Patients with symptomatic intestinal strictures.

Patients with stomas.

Patients with other local manifestations of Crohn's disease such as abscesses, or other disease manifestations for which surgery might be indicated, or which might preclude utilization of a CDAI to assess response to therapy (such as short gut syndrome).

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

Patients receiving total parenteral nutrition, as the sole source of nutrition, within the three weeks of screening.

Female patients whose hemoglobin is less than 8.5 g/dL or male patients who hemoglobin is less than 10.0 g/dL at screening.

Patients with a poor tolerability of venipuncture or a lack of adequate venous access for required treatments and blood sampling.

Patients who have a known hypersensitivity or allergy to psoralen (methoxsalen).

Patients who have a known hypersensitivity or allergy to both heparin and citrate products.

Female patients who are pregnant and/or lactating.

Patients who have been enrolled in any investigational study for the treatment of Crohn's disease within 4 weeks of enrollment for non-biologic therapies and within 8 weeks of enrollment for biologic therapies.

Patients who have any of the following: a co-existing melanoma, squamous cell skin carcinoma, aphakia, photosensitive disease (e.g., porphyria, systemic lupus erythematosus, or albinism), a white blood cell count greater than 25,000 mm(3), a previous splenectomy, or a clinically significant coagulation disorder.