Fludarabine, Cyclophosphamide, and Rituximab Versus Pentostatin, Cyclophosphamide, and Rituximab in Previously Untreated or Treated B-Cell Chronic Lymphocytic Leukemia Patients

INCLUSION CRITERIA: Patients will be eligible for inclusion in this study if they meet all of the following criteria: * Progressive, histologically proven B-cell CLL. * Stage II, III, or IV B-cell CLL, as defined by Appendix III. Note: The pathology or flow cytometry (of peripheral blood or a bone marrow) report, done by the local laboratory which documents these findings, must be included in the source documents. The SI must review the above pathology report or flow cytometry report results (including bone marrow aspirate analysis and CD5 and CD20 results) by fax, prior to registration, to confirm each patient's eligibility. Results should be consistent with typical B-cell CLL. If Dr. Reynolds is not available to review these documents, they must be reviewed by Dr. Nicholas J. Di Bella. * Patient must be CD20 + * Patient must be CD5+ (CD5 \>70%) * No more than 1 prior course (regimen) of chemotherapy, which can include Fludara or Rituxan * No prior radiation therapy, except for the treatment of skin cancer or a nonmalignant condition. * If patient has lymph node involvement, a CT scan confirming measurable tumor size (lymph node must be \>1 cm in its longest transverse diameter). * SI has been notified IF patient is on replacement steroids at time of registration. * Age greater than 18 years. * ECOG performance status of 0-2 (Appendix I). * Normal renal function (creatinine \<1.5 mg/dL and BUN \<25 mg/dL). * Absolute neutrophil count (ANC) greater than 1,000 cells/µL, platelet count greater than 50,000 cells/µL, and hemoglobin greater than 9 g/dL. * Bilirubin less than 2.0 mg/dL, and AST and ALT less than 5 times the upper limit of normal. * Negative serum pregnancy test within 7 days prior to registration (female patients of childbearing potential). * Agrees to use an acceptable method of birth control, if fertile patient (male or female), to avoid pregnancy for the duration of the study and for at least 3 months thereafter. * A signed Patient Informed Consent Form has been obtained. * A signed Patient Authorization Form has been obtained. EXCLUSION CRITERIA: Patients will be excluded from this study if they meet any of the following criteria: * Any disease other than histologically confirmed progressive, Stage II, III, or IV CLL. * Well differentiated lymphocytic lymphoma in nodes without lymphocytosis. * More than 1 prior course (regimen) of chemotherapy. * Any radiation for the treatment of CLL. * Any prior Nipent. * Known to be CD20 negative (CD20 \<20%). * Pregnant or lactating, or has a positive pregnancy test. * Has a history of other malignancy (other than in situ cervical cancer, carcinoma intraepithelial neoplasia, or non-melanoma skin cancer) within the last 5 years, which could affect the administration of these study drugs or assessment of current CLL. * Known to be HIV positive. * Uncontrolled thyroid disease or uncontrolled abnormal thyroid function. Note: Patients with thyroid disease that is controlled with medication may participate. * A history of recent, unstable organic heart disease or stable organic heart disease with LVEF \<50%. * A known hypersensitivity to Fludara, Nipent, Rituxan, or Cytoxan, or any component of these drugs. * Autoimmune hemolytic anemia. * Unable to comply with requirements of study.