The goal of this clinical research study is to see if high-dose chemotherapy (BEAM) and rituximab, given together with the new drug 90Y Zevalin, followed by a transplant of blood or marrow stem cells is safe. Another goal is to learn if this treatment can help decrease the chances of the cancer coming back.

BEAM chemotherapy is the standard treatment for lymphoma. BEAM is a combination of chemotherapy drugs (carmustine, cytarabine, etoposide, and melphalan). Rituximab is an antibody made from human and mouse proteins. It reacts with a certain molecule on the surface of lymphoma cells and helps the body's immune system destroy the lymphoma cells. 90Y Zevalin is also an antibody made from mouse proteins. However, it has a particle of radiation attached to it. 90Y Zevalin works by attaching to lymphoma cells, and the radiation particle destroys the lymphoma cell.

For this study, you will receive rituximab by vein followed by a dose of 111In Zevalin by vein (over 15 minutes). 111In Zevalin is different from the study drug (90Y Zevalin). 111In Zevalin has a different type of radioactive particle attached to it. This particle does not kill lymphoma cells, but it can be "seen" inside the body using a special camera (like an x-ray). 111In Zevalin is being used to predict how fast the study drug will travel in the body and how long the drug stays in the body. Doctors need to be able to see how much of the drug goes to the tumor and how much goes to normal organs to determine if it is safe to give 90Y Zevalin on an outpatient basis. A scan will be done as soon as 111In Zevalin is given and about 2-24 hours later. Scans will also be done 2-3 days later. If the radiation in the 111In Zevalin is not a threat to normal organs and bone marrow, you may receive 90Y Zevalin. Seven (7) days after the 111In Zevalin injection, you will receive a second dose of rituximab followed by a dose of 90Y Zevalin by vein (over 15 minutes).

Seven (7) days after the 90Y Zevalin injection, you will receive the BEAM combination of chemotherapy. You will receive carmustine (over 2 hours) on Day 1 of chemotherapy. You will receive cytarabine (over 2 hours) followed by etoposide (over 4 hours) twice a day on Days 2 through 5. On Day 6, you will receive melphalan (over 20 minutes). A catheter (small flexible tube) will be placed in a large vein in your chest so that the chemotherapy drugs can be given to you more easily. This is called a central venous catheter. All of the chemotherapy drugs will be given through the central venous catheter.

One day after finishing the chemotherapy, the stem cells that were collected earlier will be given back to you by vein over about 30 minutes. Starting on the same day, you will receive treatments with G-CSF by injection under the skin once a day. Treatment with G-CSF will continue until your blood counts reach a certain level.

You will receive rituximab by vein (over 6 to 8 hours) on the day after the transplant and again 1-week later.

Blood tests (about 1-2 tablespoons), urine tests, bone marrow collections, and x-rays will be done as needed to track the effects of the transplant. You will have transfusions of blood and platelets as needed. Blood tests (about 1 tablespoon) will be done once a day while you are in the hospital.

Blood tests (about 1-2 tablespoons), urine tests, bone marrow collections, x-rays, CT scans, and PET scans will be done every 3 months for 1 year and then every 6 months for 5 years to check on the status of the disease.

You will be asked to give some extra blood samples (around 1 tablespoon each) at study entry and upon return visits to M. D. Anderson. These samples will be used to test for certain molecules in the blood (HAMA and soluble CD20) and to check on the level of rituximab in the blood.

Treatment will be given in the hospital at the University of Texas (UT) MD Anderson. You will need to stay in the hospital for about 3 to 4 weeks. You should stay in the Houston area for about 2 to 4 weeks after the transplant. After that, you will need to return to Houston from time to time for blood tests, urine tests, and other exams.

This is an investigational study. This is an investigational study. 90Y-Zevalin is approved by the FDA for relapsed and refractory lymphoma. Its use in this trial, however, is investigational. All other drugs used in this study are FDA approved and are commercially available. Up to 60 participants will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Relapsed CD20-positive B-cell non-Hodgkin's lymphoma (NHL) (demonstrated in lymph nodes or bone marrow), chemosensitive (at least Partial Remission (PR)).
2. No anti-cancer therapy started within three weeks, prior to study initiation, and fully recovered from all toxicities associated with prior surgery, radiation treatments, chemotherapy, or immunotherapy. No prior Rituximab within three weeks of starting therapy.
3. No prior radioimmunoconjugate therapy.
4. If patients had prior radiation, this should have not involved more than 25% of the bone marrow.
5. An IRB-approved signed informed consent.
6. Age: 18 to 65 years of age.
7. Acceptable hematologic status within two weeks prior to patient registration, including: Absolute neutrophil count ([segmented neutrophils + bands] * total white blood count (WBC)) > 1,500/mm3. Platelet counts > 100,000/mm3.
8. Patients determined to have <10% bone marrow involvement with lymphoma within four weeks before stem cell collection as defined by bilateral aspirates and biopsies.
9. Prestudy performance status of 0, 1, or 2 according to the World Health Organization (WHO).
10. Female patients included must not be pregnant or lactating.
11. Men and women or reproductive potential who are following acceptable birth control methods (as determined by the treating physician, however abstinence is not an acceptable method).
12. Patients who have previously been treated on Phase II drugs can be included if no long-term toxicity is expected, and the patient has been off the drug for four or more weeks with no significant post treatment toxicities observed
13. Patients should have at least 4 * 106 CD34+/kg peripheral stem cells collected. Whenever possible, 1 to 2 * 106 CD34+/kg, for the first 10 patients and held for 1 year in case of graft failure. If graft failure does not occur in the first 10 patients, backup cells will not be required for subsequent patients.

Exclusion Criteria:

1. Patients with impaired bone marrow reserve, as indicated by one or more of the following: Prior myeloablative therapies with autologous bone marrow transplantation (ABMT) or peripheral blood stem cell (PBSC) rescue Platelet count < 100,000 cells/mm3 Hypocellular bone marrow Marked reduction in bone marrow precursors of one or more cell lines (granulocytic, megakaryocytic, erythroid) History of failed stem cell collection of > 4*106 CD34+/kg
2. Prior radioimmunotherapy.
3. Presence of central nervous system (CNS) lymphoma.
4. Patients with chronic lymphocytic lymphoma.
5. Patients with human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS)-related lymphoma.
6. Patients with abnormal liver function: total bilirubin > 1.5 mg/dl
7. Patients with abnormal renal function: serum creatinine > 1.6 mg/dl
8. Patients who have received prior external beam radiation therapy to >25% of active bone marrow (involved field or regional).
9. Serious nonmalignant disease or infection which, in the opinion of the investigator and/or the sponsor, would compromise other protocol objectives.
10. Corrected carbon monoxide diffusion in the lung (DLCO) <50% and forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) < 50% predicted.
11. Cardiac ejection fraction (EF) < 50% by 2-D Echogram.
12. Pleural effusions.
13. Prior radiation to lungs.
14. Abnormal cytogenetics, filter in situ hybridization (FISH) (-5, -7, 11q23)

Adverse event reporting 21 days prior to autologous stem cell transplantation (ASCT) to 8 days post transplant. Overall participation period (inclusive of Y Zevalin, BEAM/Rituximab treatment and ASCT) from March 2004 to November 2011.