• Time to next immunosuppressive agent
• Toxicity
• Infection rate
• Pharmacokinetics
• Changes in lymphocyte populations
• Survival

RATIONALE: Pentostatin may be effective in treating chronic graft-versus-host disease by stopping the immune system from rejecting donor stem cells or donor white blood cells.

PURPOSE: This phase II trial is studying how well pentostatin works in treating patients with chronic graft-versus-host disease that is refractory (not responsive) to treatment with steroids.

OBJECTIVES:

Primary

• Determine the response rate in patients with refractory chronic graft-versus-host disease treated with pentostatin.

Secondary

• Determine the time to next immunosuppressive agent (i.e., the time to progression from best response) in patients treated with this drug.
• Determine the toxicity of this drug in these patients.
• Determine the infection rate in patients treated with this drug.
• Determine the pharmacokinetics of this drug in these patients.
• Determine the changes in lymphocyte populations in patients treated with this drug.
• Determine the survival of patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive pentostatin IV over 20-30 minutes on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients who achieve a complete response after 6 courses receive 4 additional courses. Patients who achieve a partial response, minor response, or stable disease after 6 courses may receive up to 6 additional courses.

Patients are followed every 4 weeks for 1 year, every 3 months for 2 years, and then annually for 5 years.

PROJECTED ACCRUAL: Approximately 37 patients will be accrued for this study.

• Breast Cancer
• Chronic Myeloproliferative Disorders
• Gestational Trophoblastic Tumor
• Graft Versus Host Disease
• Leukemia
• Lymphoma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Neuroblastoma
• Ovarian Cancer
• Testicular Germ Cell Tumor

DISEASE CHARACTERISTICS:

• Histologically confirmed chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation or donor lymphocyte infusion

  • Progressive, quiescent, or de novo onset

• Extensive stage disease requiring systemic immunosuppressive therapy, defined according to Seattle criteria as 1 of the following:

  • Generalized skin involvement

  • Limited skin involvement or hepatic involvement with any of the following:

    • Liver histology showing chronic progressive hepatitis, bridging necrosis, or cirrhosis
    • Eye involvement (i.e., Schirmer's test with less than 5 mm wetting)
    • Involvement of minor salivary glands or oral mucosa
    • Involvement of any other organ

• Failed prior corticosteroid therapy, meeting 1 of the following criteria:

  • Progressive disease or less than a minor response in any organ system despite 2 weeks on steroid therapy at a dose of at least 1 mg/kg of methylprednisolone or equivalent
  • No response or minor response after at least 4 weeks of steroid therapy at a dose of least 0.5 mg/kg of methylprednisolone or equivalent
  • Less than a partial response after 8 weeks of steroid therapy at a dose of least 0.5 mg/kg of methylprednisolone or equivalent
  • Required a dose of least 0.5 mg/kg of methylprednisolone or equivalent after completion of at least 12 weeks of corticosteroid therapy in order to maintain a partial response or better
  • Required a dose of least 10 mg/kg of methylprednisolone or equivalent after completion of at least 18 weeks of corticosteroid therapy in order to maintain a partial response or better
  • Progressive extensive stage chronic GVHD after completion of at least 18 weeks of corticosteroid therapy and currently requiring reintroduction of corticosteroid therapy at a dose of least 10 mg/kg of methylprednisolone or equivalent OR an additional therapy (e.g., photopheresis or psoralen-ultraviolet-light [PUVA] therapy)
• Established chronic GVHD either not improving or progressing on other immunosuppressive agents allowed provided steroid refractoriness has been previously established

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• 0-3

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count greater than 1,000/mm^3
• Platelet count greater than 50,000/mm^3 (without transfusion)

Hepatic

• Not specified

Renal

• Creatinine clearance at least 30 mL/min

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No active infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• Not specified

Endocrine therapy

• See Disease Characteristics
• No concurrent corticosteroids as antiemetics

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• Concurrent continuation of other immunosuppressants administered during onset or progression of chronic GVHD is allowed
• No concurrent mechanical ventilation

• National Cancer Institute (NCI)
• Eastern Cooperative Oncology Group