Chlorambucil or Fludarabine as First-Line Therapy in Treating Patients With Previously Untreated Waldenström Macroglobulinemia, Splenic Lymphoma, or Lymphoplasmacytic Lymphoma

RATIONALE: Drugs used in chemotherapy, such as chlorambucil and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It is not yet known whether chlorambucil is more effective than fludarabine in treating Waldenström macroglobulinemia, splenic lymphoma, or lymphoplasmacytic lymphoma.

PURPOSE: This randomized phase III trial is studying chlorambucil to see how well it works compared with fludarabine as first-line therapy in treating patients with previously untreated Waldenström macroglobulinemia, splenic lymphoma, or lymphoplasmacytic lymphoma.

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.

Eligibility Criteria:
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