and falling steadily after that, assuming that the hcl was successfully treated. aggressive surveillance and prevention efforts are generally warranted, although the lifetime odds of developing a second cancer after hcl diagnosis are still less than 50%. there is also a higher risk of developing an autoimmune disease. polyarteritis nodosa has been associated with underlying hairy cell leukemia in certain cases. autoimmune diseases may also go into remission after treatment of hcl. epidemiology this disease is rare, with fewer than 1 in 10,000 people being diagnosed with hcl during their lives. men are four to five times more likely to develop hairy cell leukemia than women. in the united states, the annual incidence is approximately 3 cases per 1,000,000 men each year, and 0.6 cases per 1,000,000 women each year. most patients are white males over the age of 50, although it has been diagnosed in at least one teenager. it is less common in people of african and asian descent compared to people of european descent. it does not appear to be hereditary, although occasional familial cases that suggest a predisposition have been reported, usually showing a common human leukocyte antigen (hla) type. research directions the hairy cell leukemia consortium was founded in 2008 to address researchers' concerns about the long-term future of research on the disease. partly because existing treatments are so successful, the field has attracted very few new researchers. in 2013 the hairy cell leukemia foundation was created when the hairy cell leukemia consortium and the hairy cell leukemia research foundation joined. the hclf is dedicated to improving outcomes for patients by advancing research into the causes and treatment of hairy cell leukemia, as well as by providing educational resources and comfort to all those affected by hairy cell leukemia. three immunotoxin drugs have been studied in patients at the nih national cancer institute in the u.s.: bl22, ha22 and lmb-2. 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.