prohibitively toxic in patients intolerant of DCF (Pentostatin). Second-line therapy If a patient is resistant to either cladribine or pentostatin, then second-line therapy is pursued. Monoclonal antibodies: The most common treatment for cladribine-resistant disease is infusing monoclonal antibodies that destroy cancerous B cells. Rituximab is by far the most commonly used. Most patients receive one IV infusion over several hours each week for 4–8 weeks. Two partial and 10 complete responses resulted fromf 15 patients with relapsed disease, for a total of 80% responding. The median patient (including nonresponders) did not require further treatment for more than 3 years. This eight-dose study had a higher response rate than a four-dose study at Scripps, which achieved only 25% response rate. Rituximab has successfully induced a complete response in Hairy Cell-Variant. Rituximab's major side effect is serum sickness, commonly described as an "allergic reaction", which can be severe, especially on the first infusion. Serum sickness is primarily caused by the antibodies clumping during infusion and triggering the complement cascade. Although most patients find that side effects are adequately controlled by antiallergy drugs, some severe, and even fatal, reactions have occurred. Consequently, the first dose is always given in a hospital setting, although subsequent infusions may be given in a physician's office. Remissions are usually shorter than with the preferred first-line drugs, but hematologic remissions of several years' duration are not uncommon. Other B cell-destroying monoclonal antibodies such as alemtuzumab, ibritumomab tiuxetan and I-131 tositumomab may be considered for refractory cases. Interferon-alpha is an immune system hormone that is very helpful to a relatively small number of patients, and somewhat helpful to most patients. In about 65% of patients, the drug helps stabilize the disease or produce a slow, minor improvement for a partial response. The typical dosing schedule injects at least 3 million units of interferon-alpha (not pegylated versions) three times a week, although the original protocol began with 6 months of daily injections. Some patients tolerate IFN-alpha very well after the first fw weeks, while others find that its characteristic flu-like symptoms persist. About 10% of patients develop a level of depression. By maintaining a steadier level of the hormone in the body, daily injections might cause fewer side effects in selected patients. Drinking at least 2 liters of water each day, while avoiding caffeine and alcohol, can reduce many of the side effects. A drop in blood counts is usually