This phase II clinical trial studies how well yttrium Y 90 ibritumomab tiuxetan, rituximab, and high-dose chemotherapy followed by peripheral blood stem cell transplant in treating patients with relapsed B-cell non-Hodgkin lymphoma. Monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan and rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Radiolabeled monoclonal antibodies can find tumor cells and carry tumor-killing substances to them without harming normal cells. Giving monoclonal antibody therapy, radioimmunotherapy (RIT), and high-dose combination chemotherapy before a peripheral blood stem cell transplant may be an effective treatment for non-Hodgkin lymphoma.

PRIMARY OBJECTIVE:

I. To estimate the 2-year progression free survival.

SECONDARY OBJECTIVES:

II. To estimate the 2-year overall survival.

III. To estimate the 2-year cumulative incidence of progression.

IV. To estimate time to hematopoietic recovery, using absolute neutrophil and platelet engraftment.

V. To estimate incidence of grade 3-4 toxicities by Bearman Scale, Day 0 to Day 100.

VI. To estimate the response rate (CR/PR).

VII. To estimate 100-day treatment related mortality.

VIII. To estimate incidence of myelodysplasia and therapy related acute myeloid leukemia (AML).

IX. To descriptively compare the outcomes of patients treated on this protocol to a comparable patient population treated with chemotherapy alone.

OUTLINE: RADIOIMMUNOTHERAPY: Patients receive yttrium Y 90 ibritumomab tiuxetan intravenously (IV) following rituximab IV on day -14.

HIGH-DOSE COMBINATION CHEMOTHERAPY: Patients receive carmustine IV on days -7 and -6; etoposide IV over 1 hour twice daily (BID) and cytarabine IV over 2 hours BID on days -5 to -2; and melphalan IV on day -1.

STEM CELL TRANSPLANTATION: Patients undergo autologous peripheral blood stem cell transplant on day 0. Patients also receive rituximab on day 8*. NOTE: * Some patients may also receive rituximab on day -1. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.

Inclusion Criteria:

• All patients must have biopsy proven diagnosis of low- and intermediate-grade non-Hodgkin lymphoma (NHL) working formulation B, C,D, E, F, and G; including mantle cell lymphoma; patients with transformed lymphoma are also eligible
• Demonstrated monoclonal CD20 positive b-cell population in lymph nodes and/or bone marrow
• Patients must have relapsed after achieving a complete or partial response to prior therapy, have never responded to prior therapy or have poor risk disease
• Patients with prior bone marrow involvement must have bone marrow aspiration and biopsy within 60 days prior to stem cell collection which shows =< 10% lymphomatous involvement of total cellularity; alternatively, patients with prior bone marrow involvement should have a normal bone marrow study which shows =< 10% lymphomatous involvement within 28 days before salvage chemotherapy
• Normal renal function test with serum creatinine of < upper limit of normal (ULN), and a creatinine clearance of >= 60 ml/min (measured or calculated)
• Adequate pulmonary function as measured by forced expiratory volume in 1 second (FEV1) > 60% of predicted measured, or a diffusion capacity of carbon monoxide (DLCO) >= 50% of predicted measured
• Cardiac ejection fraction of > 50% by echocardiogram or multi gated acquisition (MUGA) scan; the left ventricular ejection fraction (LVEF) from the prestudy echocardiogram (ECHO) or MUGA may be used for eligibility purposes, even if the prestudy stress test indicated a lower LVEF
• Adequate liver function tests with a bilirubin of =< 1.5 x ULN and serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) =< 2 x ULN
• Negative human immunodeficiency virus antibody
• Eastern Cooperative Oncology Group (ECOG) performance status = 0 or 1; karnofsky performance status (KPS) >= 80
• No active central nervous system (CNS) disease or prior history of CNS disease
• Patients must have recovered from last therapy and should be at least four weeks from prior radiation or systemic chemotherapy on the day of administration of Y2B8
• After the last systemic therapeutic chemotherapy (Cytoxan, administered only for stem cell mobilization is not considered therapeutic) and prior to initiation of high dose treatment, the patient should have a baseline computed tomography (CT) scan and positron emission tomography (PET) scan done; an fluorodeoxyglucose-computed tomography (FDG/CT) scan is sufficient, however, is clinically indicated, an additional diagnostic CT may be ordered; exception: if scans were done and were negative for disease just prior to priming chemotherapy (therapeutic or nontherapeutic) and subsequent stem cell harvest, they do not need to be repeated prior to initiation of high dose treatment

Exclusion Criteria:

• Presence of human anti-Zevalin antibody (HAZA)

• Prior radioimmunotherapy

• Failure to collect adequate number of CD34+ cells >= 3 x 10^6/kg

• Abnormal cytogenetic study not related to the underlying lymphoma on the bone marrow aspirate sample prior to stem cell collection; if cytogenetics were not performed on the marrow aspirate prior to stem cell collection, cytogenetics on the peripheral blood may be performed

• Prior bone marrow transplantation

• Prior malignancy except for:

  • Adequately treated basal cell or squamous cell skin cancer
  • Adequately treated noninvasive carcinoma
  • Other cancer from which the patient has been disease-free for at least five years

• Active evidence of Hepatitis B or C infection; Hepatitis B surface antigen positive

• Patients who have had prior radiation to the lung will be excluded from the study, although mediastinal irradiation will be permitted if minimal lung is in the treatment volume

• Patients who have received > 500cGy radiation to the kidneys will be excluded from the study

• Patients who are pregnant or lactating

Up to 5 years