Also, 2-CdA is not 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.Rituximabs 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 physicians 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.
All of these protein-based drugs combine part of an anti-B cell antibody with a bacterial toxin to kill the cells on internalization. BL22 and HA22 attack a common protein called CD22, which is present on hairy cells and healthy B cells. LMB-2 attacks a protein called CD25, which is not present in HCL-variant, so LMB-2 is only useful for patients with HCL-classic or the Japanese variant. HA-22, now renamed moxetumomab pasudotox, is being studied in patients with relapsed hairy cell leukemia at the National Cancer Institute in Bethesda, Maryland, MD Anderson Cancer Center in Houston, Texas, and Ohio State University in Columbus, Ohio. Other sites for the study are expected to start accepting patients in late 2014, including The Royal Marsden Hospital in London, England.Other clinical trials are studying the effectiveness of cladribine followed by rituximab in eliminating residual hairy cells that remain after treatment by cladribine or pentostatin. It is not currently known if the elimination of such residual cells will result in more durable remissions. BRAF mutation has been frequently detected in HCL (Tiacci et al. NEJM  2011) and some patients may respond to Vemurafenib. The major remaining research questions are identifying the cause of HCL and determining what prevents hairy cells from maturing normally. See also
Annexin A1
List of cutaneous conditions

References
External links

About HCL at the US National Cancer Institute
History of HCL and the Godmother of HCL