Patients will receive a standard 5 mCi dosimetric dose of fission-derived Iodine I 131 Tositumomab. Pharmacokinetic data for the primary endpoint analysis will be derived from testing done on blood samples drawn at 12 timepoints over the first 7 days following administration of the dosimetric dose. Whole body gamma camera images will be obtained on six days following the dosimetric dose. Organ and tumor dosimetry data will be generated from gamma camera counts of specific organs and tumor. All scans will be examined by an independent review panel to evaluate biodistribution of the radionuclide.

Using the dosimetric data from three of the six imaging time points and the patient's weight, a patient-specific activity (mCi) of Iodine-131 will be calculated to deliver the desired total body dose of radiation (75 cGy). Patients will receive an infusion of unlabeled Tositumomab (450 mg) immediately followed by an infusion of the patient specific dose of tellurium-derived Iodine I 131 Tositumomab (35 mg) to deliver a total body dose (TBD) of 75 cGy. Patients will be followed closely obtaining safety information during the post-treatment period, and for response and safety at 3,6,and 12 months during the first year, annually thereafter up to five years, and annually for additional safety and outcomes information up to 10 years.

Inclusion criteria:

• At least 18 years of age.
• A histologically confirmed diagnosis of: Follicular lymphoma, Grade 1, 2, or 3, or diffuse large cell lymphoma concurrent with or following the diagnosis of follicular lymphoma (WHO/REAL classification).International Working Formulation histological equivalents include:

Follicular, small-cleaved; Follicular, mixed small-cleaved and large-cell; Follicular large-cell; or Transformed diffuse large cell lymphoma following or concurrent with a diagnosis of follicular lymphoma.

• Stage III or IV disease at the time of study entry.
• Previously untreated or recurrent lymphoma after no more than four prior qualifying therapy regimens. Qualifying chemotherapy can be found in Section 13.1, Appendix A. Steroids alone, as treatment for lymphoma, do not constitute a treatment regimen
• Performance status of at least 70% on the Karnofsky Performance Scale and an anticipated survival of at least three months. The Karnofsky Performance Scale can be found in Section 13.2, Appendix B.
• Bi-dimensionally measurable disease with at least one lesion measuring ≥2.0 cm x 2.0 cm (≥4.0 cm2) by CT scan
• Absolute B lymphocyte count (as determined by CD19 reactivity) of 30 to 350 cell/mm3 within 21 days prior to study enrollment
• Absolute neutrophil count ≥1500 cells/mm3; platelet count ≥150,000/mm3; and hemoglobin ≥10 g/dL within 21 days prior to study enrollment. Blood products and/or growth factors should not have been taken within 4 weeks prior to blood draw
• Adequate renal function (defined as serum creatinine <1.5 x upper limit of normal(ULN)) and hepatic function (defined as total bilirubin <1.5 x ULN and aspartate transaminase (AST) <5 x ULN) within 21 days of study enrollment
• Human anti-murine antibody (HAMA) negative within 21 days prior to study enrollment
• Signed IRB approved consent form prior to any study-specific procedures being implemented
• Follicular lymphoma (i.e., Grade 1,2, or 3), or diffuse large cell lymphoma concurrent with or following the diagnosis of follicular lymphoma, including follicular small cleaved, follicular mixed small-cleaved & large cell; follicular large-cell; or transformed diffuse large cell lymphoma following or concurrent with a diagnosis of follicular lymphoma.
• KPS>/=70%.
• Bidimensionally measureable disease with at least one lesion >/= 2.0 cm x 2.0 cm by CT scan.
• platelet count>/=150,000/mm3; and hemoglobin =10 g/dl within 21 days prior to study enrollment. Note: Blood products and/or growth factors should not have been taken within 4 weeks prior to blood draw.

Exclusion criteria:

• Greater than 25% of the intratrabecular marrow space involved by lymphoma in bone marrow biopsy specimens as assessed microscopically within 90 days of study enrollment. A unilateral bone marrow biopsy is adequate. The marrow core should be ≥2.0 cm in length. The procedure for bone marrow biopsy analysis of marrow involvement is found in Section 13.3, Appendix C.
• Prior chemotherapy, biologic therapy, steroids, or radiation therapy as treatment for NHL within 28 days prior to study enrollment. Subjects receiving low doses of steroids for non-neoplastic disease may enter this study. ("Low dose steroids" is defined as ≤10 mg of prednisone or equivalent per day.)
• Prior rituximab therapy within 120 days prior to study enrollment.
• Prior radioimmunotherapy
• Prior splenectomy
• Splenomegaly defined as spleen mass greater than 700 grams, where splenic mass is defined as: Spleen mass = π (X x Y x Z) / 6 Where X and Y are the greatest perpendicular diameters in cm on any single computerized axial tomography (CT) scan slice, and Z is the number of CT scan slices upon which the spleen is visible times the slice thickness in cm
• Bulky disease as defined as any unidimensional measurement of lymphomatous mass exceeding 7 cm.
• Prior malignancy other than lymphoma, except for adequately treated skin cancer, in situ cervical cancer, or other cancer for which the subject has a generally accepted risk of recurrence less than 20%.
• Central nervous system involvement by lymphoma.
• Evidence of active infection requiring IV antibiotics at the time of study enrollment.
• Known human immunodeficiency virus (HIV) infection.
• New York Heart Association Class III or IV heart disease or other serious illness that would preclude evaluation. Criteria can be found in Section 13.4, Appendix D.
• Active obstructive hydronephrosis.
• Evidence of clinically significant ascites or pleural effusion observed on screening physical exam or baseline CT scan.
• Prior myeloablative therapy.
• History of failed stem cell collection.
• Pregnant or nursing patients. Subjects of childbearing potential must have a negative serum pregnancy test within 21 days of study enrollment. Males and females of childbearing age must agree to use effective contraception for up to 12 months following the radioimmunotherapy.
• Greater than 25% of the intratrabecular marrow space involved by lymphoma in bone marrow biopsy specimens as assessed microscopically within 90 days of study enrollment.
• Prior chemotherapy, biologic therapy, steroids, or radiation therapy as treatment for their NHL within 28 days prior to study enrollment.
• Bulky disease as defined as any unidimensional measurement of lymphomatous mass exceeding 7 cm.
• Prior malignancy other than lymphoma, except for adequately treated skin cancer, in situ cervical cancer, or other cancer for which the patient has a generally accepted risk of recurrence less than 20%.
• CNS involvement by lymphoma.
• Active infection requiring IV antibiotics at study enrollment.
• Active obstructive hydronephrosis.
• Evidence of clinically significant ascites or pleural effusion observed on screening physical exam or baseline CAT scan.