Fludarabine Phosphate, Radiation Therapy, and Rituximab in Treating Patients Who Are Undergoing Donor Stem Cell Transplant Followed by Rituximab for High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

PRIMARY OBJECTIVES: I. Determine whether nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation (HCT) improves survival at 18 months for patients with fludarabine (fludarabine phosphate)-refractory, fludarabine/cyclophosphamide/rituximab (FCR)-failed, or del 17p CLL over that of historical controls (45% at 18 months) given CAMPATH-1H (alemtuzumab). SECONDARY OBJECTIVES: I. Estimate the overall response rate (complete remission \[CR\] + partial remission \[PR\]) by standard morphologic, flow cytometric, and molecular techniques. II. Assess the rate of relapse/progression. III. Define incidences of regimen-related toxicities (RRT) and infections within the first 100 days and the incidence of transplant-related mortality (TRM) within the first year. IV. Estimate incidences of grade II-III and III-IV acute graft-versus-host disease (GVHD) and chronic GVHD. V. Determine whether the addition of rituximab to the nonmyeloablative conditioning and allogeneic HCT improves survival at 18 months over our historical data (57% at 18 months). VI. Determine the incidence of serious adverse events with the addition of rituximab in comparison to historical data of unrelated nonmyeloablative HCT. VII. Evaluate the pharmacokinetics of rituximab. VIII. Evaluate B-cell and T-cell immune reconstitution in comparison to historical data of unrelated nonmyeloablative HCT. IX. Describe donor and host polymorphisms of the FCgammaRIIIa receptor and cluster of differentiation (CD)32 and evaluate their impact on disease response and relapse. X. Investigate the mechanism of disease resistance in relapsed/nonresponding patients. XI. Isolate donor cytotoxic T lymphocytes specific for host minor histocompatibility antigens. OUTLINE: Patients receive a conditioning regimen comprising fludarabine phosphate intravenously (IV) on days -4 to -2 and rituximab IV on days -3, 10, 24, and 38. Patients undergo single fraction low-dose total-body irradiation (TBI) on day 0. After completion of TBI, patients undergo allogeneic hematopoietic stem cell transplantation (HSCT) on day 0. Patients then receive rituximab IV on days 10, 24, and 38. Patients receive an immunosuppressive regimen comprising cyclosporine orally (PO) twice daily (BID) on days -3 to 56 followed by a taper to day 180 (related recipients) or on days -3 to 100 followed by a taper to day 180 (unrelated recipients). Patients also receive mycophenolate mofetil PO BID on days 0-27 (related recipients) or three times daily (TID) on days 0-40 followed by a taper to day 96 (unrelated recipients). After completion of study treatment, patients are followed up at 6 months, 1 year, 18 months, 2 years, and then annually thereafter.