Efalizumab in Treating Patients With Graft-Versus-Host Disease of the Skin That Did Not Respond to Previous Steroids (NRR)

Inclusion Criteria:

1. Skin disease

   • Patients must demonstrate evidence of an erythematous maculopapular rash which is felt to be clinically consistent with graft-versus-host disease. Patients must undergo skin biopsy prior to enrollment. Because the pathological findings of GVHD may be equivocal (6) a biopsy which is felt to be consistent with GVHD will be considered adequate.
   • Consider sclerodermatous skin changes may be present but will not by themselves adequate for enrollment. Patients must exhibit signs of an active inflammatory rash.

2. Liver disease

   • Although hepatic involvement is not required for study participation, patients with concomitant GVHD of the liver are encouraged to enroll. All patients with hepatic GVHD must also demonstrate cutaneous disease. Patients with liver dysfunction are encouraged but not required to undergo hepatic biopsy in order to document that liver injury is the result of GVHD. Patients with a pretreatment serum bilirubin ≥ 2.0 mg/dL and biopsy-confirmed cutaneous GVHD will be assumed to demonstrate hepatic GVHD if no other cause for the liver function test (LFT) elevation can be identified.

3. Age ≥ 18 years
4. Patients must be ≥ 30 days removed from allogeneic hematopoietic stem cell transplant in order to allow for engraftment. Patients receiving peripheral blood stem cells and/or bone marrow will be eligible, regardless of the degree of human leukocyte antigen (HLA) matching.

5. Steroid refractory disease

   • All patients must demonstrate evidence of steroid refractory graft-versus host disease of the skin or liver. In an effort to conform to a standard definition of steroid refractory disease, we will base our criteria on those described in a large intergroup trial examining the effectiveness of pentostatin for steroid refractory chronic GVHD (31). Because the present study, however, is designed to include patients with both acute and chronic GVHD based on traditional disease classification criteria, the required time intervals necessary to define steroid-refractoriness have been shortened. Patients will be considered steroid refractory if any one of the following conditions is met:

   • Worsening skin or liver disease despite 1 week on the equivalent of 1mg/kg of methylprednisolone
   • Failure to achieve a 50% reduction in the body surface area involved by GVHD or a 50% reduction in the total serum bilirubin after 4 weeks on the equivalent of at least 0.5 mg/kg of methylprednisolone
   • Requirement of ≥ the equivalent of 0.5mg/kg of methylprednisolone to maintain a response after 8 weeks of steroid therapy
   • Patients with progression of cutaneous or hepatic GVHD after a prior history of treatment with at least 8 weeks of corticosteroids now requiring the reintroduction of corticosteroids (> the equivalent of 10mg/day of methylprednisolone)
   • Patients with GVHD not improving or progressing on alternative immunosuppressive agents will be eligible if steroid refractoriness has been established previously
6. Required initial laboratory values:

Absolute neutrophil count (ANC) > 1000/μL Platelet count ≥ 20,000/μL Serum creatinine ≤ 3.0 mg/dL

Exclusion Criteria:

1. Non-pregnant and non-nursing

   • Treatment under this protocol would expose an unborn child to significant risks. Women and men of reproductive potential must agree to use an effective means of birth control.

2. No HIV infection

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 2 terminal half-lives since prior and no concurrent infliximab, daclizumab, etanercept, rituximab, antithymocyte globulin (ATG), or denileukin diftitox