From a recent review article:
Since the first clear description of HCL by Bouroncle in 1958 there has been a step change in the understanding of the biology of the disease and improvement in treatment. In the 1980s a review of cases reported a median survival of only 4 years. Life expectancy for patients now is the same, or very close to that of a normal age-matched population.
Diagnosis of HCL is usually straightforward with a typical clinical presentation and characteristic morphological and immunophenotypic profile of hairy cells. Once the possibility of HCL is entertained it is not difficult to confirm following careful examination of blood and bone marrow. Some of the more unusual clinical manifestations of the disease are discussed in this volume.
Despite the rarity of HCL and consequent difficulty in conducting large clinical trials, relatively early progress was made with the recognition that purine analogues could deliver a very high rate (80%) of durable remissions. The drugs pentostatin and cladribine have been the mainstay of treatment since the 1980s. However, about half of the patients will relapse and some will eventually become refractory to these agents. Until recently treatment options for patients with purine-analogue- refractory disease have been limited. The introduction of Monoclonal antibodies, given in combination or as an immunoconjugate, have been able to further prolong disease response and survival for patients.
One of the most exciting discoveries was the description, in 2011, of the V600E mutation of BRAF in virtually all cases of classical hairy cell leukaemia. This constitutively activates the MAPK pathway and appears to be the key genetic driver of the disease. Indeed, inhibition of BRAF in vitro reverses the classical morphological and genetic features of the hairy cell and induces hairy cell death. This translates into therapeutic activity in vivo , which has recently been confirmed by the publication of the successful results of a combined clinical trial of vemurafenib in relapsed HCL by Italian and US investigators.