• Response to therapy (complete and partial response rates) [ Designated as safety issue: No ]
  
• Duration of response [ Designated as safety issue: No ]
  

• Improvement in hematological parameters [ Designated as safety issue: No ]
  
• Toxicity [ Designated as safety issue: Yes ]
  
• Quality of life as assessed by the European Organization for Research and Treatment of Cancer Quality of Life-30 questionnaire [ Designated as safety issue: No ]
  
• Survival [ Designated as safety issue: No ]
  

OBJECTIVES:

• Compare the efficacy of first-line therapy comprising chlorambucil vs fludarabine phosphate in patients with previously untreated Waldenström macroglobulinemia, splenic lymphoma with villous lymphocytes, or non-IgM lymphoplasmacytic lymphoma.

OUTLINE: This is a multicenter study. Patients are stratified according to disease (Waldenström macroglobulinemia vs splenic lymphoma with villous lymphocytes vs non-IgM lymphoplasmacytic lymphoma). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral chlorambucil on days 1-10. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive fludarabine phosphate orally or IV on days 1-5. Treatment repeats every 28 days for 3-6 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo quality of life assessment at baseline.

DISEASE CHARACTERISTICS:

• Diagnosis of Waldenström macroglobulinemia, splenic lymphoma with villous lymphocytes (SLVL), or non-IgM lymphoplasmacytic lymphoma based on morphological and immunophenotypic criteria

  • Bone marrow should be assessed by two-color flow cytometry for the expression of the following antigens:

    • Surface Ig
    • CD19
    • CD20
    • CD5
    • CD10
    • CD23

• Previously untreated disease requiring therapeutic intervention (as judged by the primary physician), as indicated by ≥ 1 of the following:

  • Hemoglobin < 10 g/dL
  • ANC < 1.5 x 10^9/L
  • Platelet count < 150 x 10^9/L
  • Clinical evidence of hyperviscosity in terms of neurological or ocular disturbance
• Patients with disease detected by clonal cells alone are not eligible

PATIENT CHARACTERISTICS:

• Performance status 0-2
• Life expectancy > 6 months
• Serum creatinine < 200 mmol/L
• AST and ALT < 2 times upper limit of normal
• Negative direct Coomb's test
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 6 months after completion of study therapy
• No severe or life-threatening cardiac, pulmonary, neurological, psychiatric, or metabolic disease
• No other concurrent malignancy
• No AIDS or AIDS-related complex
• No evidence of active hepatitis C infection

PRIOR CONCURRENT THERAPY:

• Prior plasmapheresis for control of clinically significant hyperviscosity allowed
• Prior splenectomy for SLVL allowed