RATIONALE: Etanercept, mycophenolate mofetil, denileukin diftitox, pentostatin, prednisone, or methylprednisolone may be an effective treatment for graft-versus-host disease caused by a donor stem cell transplant.

PURPOSE: This randomized phase II trial is studying etanercept, mycophenolate mofetil, denileukin diftitox, or pentostatin combined with prednisone or methylprednisolone to compare how well they work in treating patients with acute graft-versus-host disease who have undergone a previous donor stem cell transplant.

OBJECTIVES:

Primary

• Compare the complete response rate at 4 weeks in patients with acute graft-versus-host disease (GVHD) who have undergone a prior allogeneic hematopoietic stem cell transplant treated with etanercept vs mycophenolate mofetil vs denileukin diftitox vs pentostatin in combination with prednisone or methylprednisolone.

Secondary

• Compare the 4-week partial response rate, mixed response rate, and disease progression in patients treated with these regimens.
• Compare the 2-week treatment failure rate (no response, progression, or mortality) in patients treated with these regimens.
• Compare the incidence of GVHD flares requiring increased therapy before 90 days in these patients.
• Compare the incidence of discontinuation of immune suppression without flare by days 90, 180, and 270 post therapy in these patients.
• Compare the incidence of chronic GVHD by 9 months in patients treated with these regimens.
• Compare the 6- and 9-month overall survival post initiation of therapy in these patients.
• Compare the incidence of systemic infections within 3 months of initiation of therapy in these patients.
• Compare the incidence of Epstein-Barr virus-associated lymphoma in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 4 treatment arms.

• Arm I: Patients receive etanercept subcutaneously twice weekly for up to 4 weeks. Patients also receive oral prednisone or methylprednisolone IV 2-3 times a day for at least 1 week followed by a taper, for responding patients, over approximately 9 weeks.
• Arm II: Patients receive mycophenolate mofetil orally or IV over 2 hours twice daily for approximately 8-10 weeks or for as long as graft-versus-host disease is active. Patients also receive prednisone or methylprednisolone as in arm I.
• Arm III: Patients receive denileukin diftitox IV over 1 hour on days 1, 3, 5, 15, 17, and 19. Patients also receive prednisone or methylprednisolone as in arm I.
• Arm IV: Patients receive pentostatin IV over 15-30 minutes on days 1-3 and 15-17. Patients also receive prednisone or methylprednisolone as in arm I.

After completion of study treatment, patients are followed periodically for 9 months.

PROJECTED ACCRUAL: A total of 180 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of acute graft-versus-host disease (GVHD)
• De novo grade B-D GVHD requiring systemic therapy within 24 hours of diagnosis
• No isolated upper gastrointestinal GVHD as sole manifestation of acute GVHD
• No isolated limited skin GVHD (stage I or II) as sole manifestation of acute GVHD
• Has undergone prior allogeneic hematopoietic stem cell transplant* using 1 of the following:
• Bone marrow
• Peripheral blood stem cells
• Cord blood NOTE: *Nonmyeloablative stem cell transplant allowed
• No GVHD after donor lymphocyte infusion
• No clinical syndrome resembling de novo chronic GVHD after allotransplant

PATIENT CHARACTERISTICS:

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count > 500/mm^3

Hepatic

• Not specified

Renal

• Creatinine clearance > 30 mL/min

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of intolerance to any of the study drugs
• No uncontrolled infection
• Bacterial or viral infections must be controlled by definitive therapy and show no signs of progressing infection* within 72 hours of study entry
• Fungal infections must be controlled with definitive systemic antifungal therapy and show no signs of progressing infection* within 1 week of study entry NOTE: *Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs, or radiographic findings attributable to infection. Persistent fever without other signs or symptoms will not be interpreted as progressing infection.

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• More than 7 days since prior denileukin diftitox
• More than 7 days since prior etanercept
• Prior antithymocyte globulin allowed

Chemotherapy

• More than 7 days since prior pentostatin
• Prior methotrexate allowed

Endocrine therapy

• Prior corticosteroid therapy for treatment of acute GVHD allowed provided patient was treated with ≥ 1 mg/kg/day of methylprednisolone for no more than 24 hours
• Other prior corticosteroids allowed

Other

• No other prior immunosuppressive therapy for treatment of acute GVHD
• More than 7 days since prior mycophenolate mofetil
• More than 30 days since prior investigational agents for GVHD
• More than 30 days since prior prophylactic agents for GVHD
• Prior cyclosporine, tacrolimus, or sirolimus allowed
• Concurrent cyclosporine or tacrolimus allowed