Background: * Researchers are attempting to develop new treatments for hairy cell leukemia (HCL) that has not responded well to or has recurred after standard HCL therapies. One nonstandard treatment for HCL is rituximab, an antibody that binds to the cancer cells and helps the immune system destroy them. By combining rituximab with other anti-cancer drugs, researchers hope to determine whether the combined drugs are successful in treating HCL. * Pentostatin and bendamustine are two anti-cancer drugs that have been used to treat different kinds of blood and immune system cancers. Bendamustine is approved to treat other kinds of leukemia and lymphoma, but it has not been used to treat HCL. Pentostatin has been used for more than 20 years to treat HCL, but it has not been combined with rituximab in official clinical trials. Objectives: * To determine whether rituximab with either pentostatin or bendamustine is a more effective treatment for HCL than rituximab alone. * To determine whether pentostatin or bendamustine is a more effective treatment for HCL when combined with rituximab. Eligibility: \- Individuals at least 18 years of age who have been diagnosed with hairy cell leukemia that has not responded well to or has relapsed after standard HCL therapies. Design: * The study will last for four treatment cycles of 28 days each. * Prior to the study, participants will be screened with a full medical history and physical exam, bone marrow biopsy (if one has not been performed in the last 6 months), computed tomography (CT) or ultrasound scan, tumor measurements, and other tests as required by the researchers. Participants will provide blood and urine samples at this time as well. * Rituximab with bendamustine: Participants will receive rituximab on Days 1 and 15 of each cycle and bendamustine on Days 1 and 2 of each cycle, for a total of four cycles. * Rituximab with pentostatin: Participants will receive rituximab on Days 1 and 15 of each cycle and pentostatin on rituximab on Days 1 and 15 of each cycle, for a total of four cycles. * Participants will have regular tests during the treatment cycles, including bone marrow biopsies and CT or ultrasound scans. Participants will also provide regular blood and urine samples to assess the results of treatment.
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Number of Participants Receiving Pentostatin + Rituximab and Bendamustine + Rituximab Who Achieve a Complete Remission (CR) + Partial Response (PR)
Timeframe: At end of treatment, approximately 6 months