Rituximab, Fludarabine, Cyclophosphamide, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Relapsed B-Cell Non-Hodgkin's Lymphoma

DISEASE CHARACTERISTICS:

• Histologically confirmed CD20-positive B-cell non-Hodgkin's lymphoma (NHL), including any of the following subtypes:
• Indolent NHL, including any of the following:
• Follicular
• Lymphoplasmacytoid
• Marginal zone
• Mantle cell NHL
• Transformed B-cell NHL
• In at least first relapse with an indication for systemic antineoplastic treatment, as defined by the following:
• Local or constitutional (B-) symptoms
• Hypersplenism due to splenic involvement
• Bulky disease (> 7.5 cm in diameter)
• Impending medical problems derived from rapid disease progression within the past 6 months, as defined by an observed or anticipated > 50% increase in the sum of the areas calculated from multiplying the greatest perpendicular diameters of each lesion
• Measurable lesions of lymphoma infiltration
• Medically ineligible for high-dose treatment followed by autologous stem cell support
• Adequate bone marrow cellularity (> 15% of marrow area covered by hematopoiesis)
• No CNS, leptomeningeal, spinal cord, or testes lymphoma involvement
• No lymphoma lesion mandating emergency radiotherapy
• No clinical, cytological, cytogenetic, or histopathologic indication of myelodysplastic syndrome
• If there is bone marrow infiltration detected prior to chemoimmunotherapy, patient must undergo a repeat bone marrow biopsy prior to planned treatment with radioimmunotherapy to verify the level of bone marrow infiltration is < 25%

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 3 months
• Absolute neutrophil count > 1,500/mm³
• Platelet count > 150,000/mm³
• Hemoglobin > 9 g/dL
• Creatinine < 1.5 times upper limit of normal (ULN)
• Bilirubin < 2 times ULN
• ALT and AST < 2 times ULN
• Albumin > 2.5 g/dL
• INR < 1.5
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 12 months after completion of study treatment
• No concurrent severe and/or uncontrolled medical disease that would preclude study compliance, including any of the following:
• Uncontrolled diabetes
• Congestive heart failure
• Chronic renal disease
• Active uncontrolled infection
• No bleeding risks or disorders, including any of the following:
• CNS abnormalities suggesting an increased susceptibility for hemorrhage, including recent history of stroke as demonstrated by cranial contrast-enhanced CT scan
• Severe arrhythmia or uncontrolled hypertension
• Myocardial infarction within the past 6 months
• Diabetic retinopathy with history of symptomatic hemorrhage
• Known and potentially active gastrointestinal bleeding foci
• Concurrent anticoagulant medication that must be continued even with platelet count < 20,000/mm³ (e.g., following mitral valve replacement, anti-phospholipid syndrome, or recurrent venous thromboembolism)
• Other congenital or acquired hemorrhagic diatheses
• No ongoing autoimmune hemolytic anemia
• No known presence of anti-murine antibody reactivity
• No known hypersensitivity to murine or chimeric antibodies or proteins
• No known HIV infection
• No psychiatric illness that would preclude study requirements
• No other malignant disorder within the past 10 years except basal cell carcinoma of the skin or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior therapy
• No more than 4 prior systemic anti-lymphoma regimens (including single-agent rituximab)
• At least 2 months since prior systemic anti-lymphoma treatment (including single-agent rituximab)
• No prior radioimmunotherapy
• No prior autologous or allogeneic hematopoietic stem cell transplantation
• No prior treatment with purine analogues that has not resulted in remission for > 1 year
• No prior anti-CD20 radioimmunoconjugate therapy
• More than 5 years since prior radiotherapy to extensive fields covering lymph node regions on both sides of the diaphragm or > 50% of the spinal column
• More than 4 weeks since prior surgery
• No concurrent oral anticoagulant therapy