• Complete, partial, and overall response rates [ Designated as safety issue: No ]
• Clinical response [ Designated as safety issue: No ]
• Toxic effects [ Designated as safety issue: Yes ]

• Complete, partial, and overall response rates
• Clinical response
• Toxic effects

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of methotrexate with or without cyclophosphamide in treating patients who have lymphocytic leukemia with neutropenia or anemia.

OBJECTIVES:

• Determine the complete, partial, and overall response rates to methotrexate in patients with large granular lymphocytic (LGL) leukemia presenting with neutropenia or anemia.
• Determine the complete, partial, and overall response rates to cyclophosphamide in the patients who fail to respond to methotrexate.
• Assess the association of clinical response with increased sensitivity of leukemic LGL to Fas-dependent apoptosis, reduction in levels of Fas ligand, and disappearance of leukemic clone.
• Determine the toxic effects of methotrexate and cyclophosphamide in these patients.

OUTLINE: Patients are stratified according to symptom (neutropenia vs anemia).

Patients receive oral methotrexate once a week for 4 months and oral prednisone daily for 54 days. Patients who show a partial response to methotrexate may continue this therapy for up to 1 year. Patients who do not respond to this therapy after 4 months then receive oral cyclophosphamide daily for up to 1 year and oral prednisone daily for 54 days.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 38-88 patients will be accrued for this study.

• Drug: cyclophosphamide
• Drug: methotrexate
• Drug: prednisone

DISEASE CHARACTERISTICS:

• Cytologically proven T-cell large granular lymphocytic (LGL) leukemia

  • Absolute LGL count greater than 500/mm3 (peripheral blood only)
  • CD3+ and CD57+ cells greater than 400/mm3 OR
  • CD8+ cells greater than 650/mm3
  • Clonal T-cell receptor gene rearrangement

  • At least 1 of the following:

    • Severe neutropenia (neutrophil count less than 500/mm3)
    • Neutropenia associated with recurrent infections
    • Symptomatic anemia
    • Transfusion dependent anemia

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 2 years

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• SGOT no greater than 1.5 times normal

Renal:

• Creatinine no greater than 2.0 mg/dL

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior or concurrent malignancy within past 5 years except inactive nonmelanomatous skin cancer or carcinoma in situ of the cervix
• No other serious medical illness
• No concurrent psychiatric condition

PRIOR CONCURRENT THERAPY:

• No prior oral methotrexate or cyclophosphamide