This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purposes of this study are to 1> evaluate the safety and effectiveness of a treatment regimen using an antibody attached to a radioactive substance (IDEC-Y2B8) in combination with high-dose chemotherapy (with the drugs BCNU, Etoposide, Ara-C and Melphalan, or BEAM) followed by autologous stem cell transplant (ASCT); and 2> to evaluate the short-term and long-term complications of this regimen in patients diagnosed with non-Hodgkin's lymphoma. Non-Hodgkin's lymphoma is a malignancy of B lymphocytes, which are the white blood cells that normally make antibodies that help fight infections. Although remission (no evidence of disease by standard clinical tests) can occur with conventional chemotherapy and/or radiation therapy, the length of remission is usually short and relapses (return of disease) occur. The outlook for patients with relapsed lymphoma is poor. Recent studies have shown that intensive, high-dose chemotherapy followed by autologous stem cell transplantation (ASCT), can produce long-term remission in patients with relapsed lymphoma. BEAM is one of the most commonly used high-dose regimens for preparation of ASCT. ASCT involves collection of the subject's stem cells (immature cells that can become blood cells) before therapy and return of these cells to the subject (through a vein) after therapy is over. However, relapses also occur with this treatment regimen. The antibody, Rituximab (Rituxan or IDEC-C2B8) has been shown to produce remission in about half of the B-cell lymphoma subjects treated. In previous studies, this antibody has been shown to selectively locate and destroy B-cells, including B-cell lymphoma, and to cause drug-resistant lymphoma cells to become sensitive to chemotherapy. Adding a radioactive substance called Yttrium to IDEC-Y2B8, (creating a radioactive combination called IDEC-Y2B8) allows radiation to be carried directly to tumor sites which can increase the anti-tumor effect. In a past study of IDEC-Y2B8, about two-thirds of the subjects with B-cell lymphoma had shown greater than 50% shrinkage of the tumor after treatment and in one-fourth of them all the tumor was gone. The duration of response was about 12 months. The present study will use intensive, high-dose chemotherapy (BEAM) and IDEC-Y2B8, followed by ASCT. This study will try to determine the safety and effectiveness of this combination regimen.
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