Cladribine With Simultaneous or Delayed Rituximab to Treat Hairy Cell Leukemia

* INCLUSION CRITERIA: Evidence of Hairy Cell Leukemia (HCL) by flow cytometry, reviewed by the Laboratory of Pathology, National Cancer Institute (NCI), including positivity for Cluster of Differentiation 19 (CD19), Cluster of Differentiation 22 (CD22), cluster of differentiation 20 (CD20), and integrin alpha X (CD11c). Bone marrow biopsy (BMBx) consistent with HCL, reviewed by Laboratory of Pathology, NCI. BMBx may be negative in hairy cell leukemia variant, (HCLv) in patients with increasing peripheral blood HCLv cells and spleen size. Treatment indicated based on demonstration of at least one of the following, no more than 4 weeks from the time of enrollment, and no less than 6 months after prior purine analog and no less than 4 weeks after other prior treatment, if applicable. * Neutropenia (absolute neutrophil count (ANC) less than 1000 cells/microl). * Anemia (hemoglobin (Hgb) less than 10g/dL). * Thrombocytopenia (Platelet (Plt) less than 100,000/microl). * Absolute lymphocyte count (ALC) of greater than 5,000 cells/microL * Symptomatic splenomegaly. * Enlarging lymph nodes greater than 2cm. * Repeated infections requiring oral or intravenous (i.v.) antibiotics. * Patients who have eligible blood counts within 4 weeks from enrollment will not be considered ineligible if subsequent blood counts prior to enrollment fluctuate and become ineligible up until the time of enrollment. No prior purine analog therapy except up to 1 prior course of cladribine. No prior rituximab unless HCLv patient. Eastern Cooperative Oncology Group (ECOG) performance status (78) of 0-3. Patients must be able to understand and give informed consent. Women of child-bearing age and all men must use birth control of any type until at least 12 months after the last dose of therapy. Creatinine less than or equal to 1.5 or creatinine clearance greater than or equal to 60 ml/ml. Bilirubin less than or equal to 2 unless consistent with Gilbert's (total/direct greater than 5), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 times upper limits of normal. No other therapy (i.e. chemotherapy, interferon) for 4 weeks prior to study entry, or cladribine for 6 months prior to study entry. Age at least 18 Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months after completion of treatment. Subject has provided written informed consent Patients must be willing to co-enroll in the investigators companion protocol 10-C-0066 titled Collection of Human Samples to Study Hairy Cell and other Leukemias, and to Develop Recombinant Immunotoxins for Cancer Treatment. EXCLUSION CRITERIA: Presence of active untreated infection Uncontrolled coronary disease or New York Heart Association Classification (NYHA) class III-IV heart disease. Known infection with HIV. Hepatitis B is allowed only if viral load is undetectable and if on anti-hepatitis B therapy like Entecavir. Hepatitis C is allowed only if viral load is undetectable, and if the patient has received curative therapy. Patients with documented history of no response to cladribine, and without 50% improvement in platelets, hemoglobin or granulocytes. This exclusion does not apply to HCLv. These patients are eligible regardless of prior response to chlorodeoxyadenosine (CDA) Pregnant or lactating women. Presence of active 2nd malignancy requiring treatment. 2nd malignancies with low activity which do not require treatment (i.e. low-grade prostate cancer, basal cell or squamous cell skin cancer) do not constitute exclusions. Inability to comply with study and/or follow-up procedures. Presence of central nervous system (CNS) disease, which is symptomatic. At the Investigators discretion, receipt of a live vaccine within 4 weeks prior to randomization. Efficacy and/or safety of immunization during periods of B-cell depletion have not been adequately studied. It is recommended that a patients vaccination record and possible requirements be reviewed. Per the investigator's discretion, the patient may have any required vaccination/booster administered at least 4 weeks prior to the initiation of study treatment. Review of the patient s immunization status for the following vaccinations is recommended: tetanus; diphtheria; influenza; pneumococcal polysaccharide; Varicella; measles, mumps and rubella (MMR); and hepatitis B. Patients who are considered to be at high risk for hepatitis B virus (HBV) infection and for whom the investigator has determined that immunization is indicated should complete the entire HBV vaccine series at least 4 weeks prior to participation in the study.