{"entity":{"id":"hairy-cell-leukemia","kind":"cancer","name":"Hairy cell leukaemia","aka":[],"tldr":"Hairy cell leukaemia is a rare, slow B-cell leukaemia with a single defining mutation (BRAF V600E) that is unusually curable: one week of a purine analogue puts most people into remission for years, and BRAF drugs rescue those who relapse.","summary":"Classic hairy cell leukaemia (HCL) is a mature B-cell neoplasm with a distinctive morphology and immunophenotype (CD11c, CD25, CD103, CD123, annexin A1) and BRAF V600E in essentially all cases (Tiacci 2011); the variant HCL-v lacks BRAF V600E, is CD25-negative, and behaves worse (often MAP2K1-mutant). Patients present with pancytopenia, splenomegaly and infections.\n\nPurine analogues (cladribine or pentostatin) give complete remission in 80-90% with a single course, and adding rituximab (concurrent or delayed) deepens responses and achieves MRD negativity in most (Chihara et al.). Relapse is treated with a second purine analogue course plus rituximab; BRAF inhibition (vemurafenib ± rituximab) gives durable remissions in multiply relapsed disease (Tiacci 2021, NEJM), and BRAF+MEK combinations are an option. Moxetumomab pasudotox (anti-CD22 immunotoxin) was approved in 2018 and withdrawn commercially in 2023. Ibrutinib has modest activity. Overall survival is now close to age-matched controls.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Hairy_cell_leukemia","links":[{"label":"NCCN Guidelines: Hairy Cell Leukemia","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1481"},{"label":"Hairy Cell Leukemia Foundation","url":"https://www.hairycellleukemia.org/"},{"label":"Tiacci 2011 NEJM","url":"https://doi.org/10.1056/NEJMoa1014209"}],"tags":["gap-fill","haematologic"],"related":["cll","cml"],"cancers":[],"sections":[],"technologies":["kinase-inhibitors","monoclonal-antibody","flow-cytometry-mrd","cytotoxic-chemotherapy"],"targets":["braf","cd20","cd22","cd123","btk"],"drugs":["cladribine","rituximab","vemurafenib","dabrafenib-trametinib","moxetumomab-pasudotox","ibrutinib","interferon-alfa"],"companies":["roche-genentech","astrazeneca"],"institutions":[],"pathways":["ras-mapk"],"terms":["mrd"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-tiacci-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"group":"haematologic","burden":"Hairy cell leukaemia causes about 1,000-1,200 cases per year in the US (~2% of leukaemias); median age ~55, 4:1 male.","subtypes":["Classic HCL (BRAF V600E)","HCL variant (BRAF-wild-type, CD25-negative, MAP2K1 mutations)","IGHV4-34 HCL (poor risk)"],"biomarkers":["BRAF V600E (IHC VE1, PCR, ddPCR)","Flow cytometry: CD11c, CD25, CD103, CD123","MRD by flow or BRAF ddPCR","IGHV4-34 usage","MAP2K1 mutations (variant)"],"standardOfCare":[{"setting":"First line, symptomatic","approach":"Cladribine (5-7 days) or pentostatin, with rituximab concurrent or delayed (improves MRD-negative CR).","refs":["cladribine","rituximab"],"guideline":{"nccn":"Category 1 (cladribine ± rituximab)","version":"NCCN Guidelines: Hairy Cell Leukemia","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1481"}},{"setting":"Relapse after >2 years","approach":"Repeat purine analogue + rituximab.","refs":["cladribine","rituximab"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: Hairy Cell Leukemia"}},{"setting":"Early relapse or refractory","approach":"Vemurafenib + rituximab (or dabrafenib-trametinib); ibrutinib; clinical trial. Moxetumomab pasudotox produced durable remissions but was withdrawn from sale in 2023 and is no longer available.","refs":["vemurafenib","rituximab","dabrafenib-trametinib","ibrutinib","moxetumomab-pasudotox"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: Hairy Cell Leukemia"}}],"stateOfArt":["One week of cladribine remains one of the most effective single treatments in oncology.","BRAF V600E is universal in classic HCL; vemurafenib-rituximab produces MRD-negative remissions in most relapsed patients without chemotherapy.","Life expectancy is near normal; the residual problems are infection during induction and the aggressive variant."],"history":[{"year":1958,"title":"Bouroncle describes 'leukemic reticuloendotheliosis'","refs":[]},{"year":1984,"title":"Interferon alfa: first effective therapy","refs":["interferon-alfa"]},{"year":1990,"title":"Cladribine: durable remissions after one course (Piro, NEJM)","refs":["cladribine"]},{"year":2011,"title":"BRAF V600E found in all classic HCL (Tiacci, NEJM)","refs":["braf"]},{"year":2015,"title":"Vemurafenib active in relapsed HCL","refs":["vemurafenib"]},{"year":2018,"title":"Moxetumomab pasudotox approved","note":"First CD22 immunotoxin; withdrawn from the US market in 2023 for commercial reasons.","refs":["moxetumomab-pasudotox"]},{"year":2021,"title":"Vemurafenib + rituximab: chemo-free durable remissions (NEJM)","refs":["vemurafenib","rituximab"]}],"pipeline":["vemurafenib","dabrafenib-trametinib"],"openProblems":["Variant HCL and IGHV4-34 disease respond poorly to purine analogues.","Infection risk during induction neutropenia.","Whether MRD eradication should be a treatment goal."],"parent":"leukaemia"},"route":"/cancers/hairy-cell-leukemia/","neighbours":{"cancer":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"cml","kind":"cancer","name":"Chronic myeloid leukaemia (CML)","route":"/cancers/cml/"},{"id":"leukaemia","kind":"cancer","name":"Leukaemia (all types)","route":"/cancers/leukaemia/"},{"id":"splenic-b-cell-lymphoma-leukaemia-prominent-nucleoli","kind":"cancer","name":"Splenic B-cell lymphoma/leukaemia with prominent nucleoli (formerly B-cell prolymphocytic leukaemia and hairy cell leukaemia variant)","route":"/cancers/splenic-b-cell-lymphoma-leukaemia-prominent-nucleoli/"},{"id":"splenic-marginal-zone-lymphoma","kind":"cancer","name":"Splenic marginal zone lymphoma","route":"/cancers/splenic-marginal-zone-lymphoma/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"},{"id":"flow-cytometry-mrd","kind":"technology","name":"Multiparameter flow cytometry MRD","route":"/technologies/flow-cytometry-mrd/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"ada","kind":"target","name":"Adenosine deaminase (ADA)","route":"/targets/ada/"},{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"},{"id":"btk","kind":"target","name":"BTK (Bruton tyrosine kinase)","route":"/targets/btk/"},{"id":"cd123","kind":"target","name":"CD123","route":"/targets/cd123/"},{"id":"cd20","kind":"target","name":"CD20","route":"/targets/cd20/"},{"id":"cd22","kind":"target","name":"CD22","route":"/targets/cd22/"},{"id":"ifnar1","kind":"target","name":"Interferon alpha receptor (IFNAR1)","route":"/targets/ifnar1/"}],"drug":[{"id":"cladribine","kind":"drug","name":"Cladribine","route":"/drugs/cladribine/"},{"id":"dabrafenib-trametinib","kind":"drug","name":"Dabrafenib + trametinib","route":"/drugs/dabrafenib-trametinib/"},{"id":"ibrutinib","kind":"drug","name":"Ibrutinib","route":"/drugs/ibrutinib/"},{"id":"interferon-alfa","kind":"drug","name":"Interferon alfa-2a/2b","route":"/drugs/interferon-alfa/"},{"id":"moxetumomab-pasudotox","kind":"drug","name":"Moxetumomab pasudotox","route":"/drugs/moxetumomab-pasudotox/"},{"id":"pentostatin","kind":"drug","name":"Pentostatin","route":"/drugs/pentostatin/"},{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"},{"id":"vemurafenib","kind":"drug","name":"Vemurafenib","route":"/drugs/vemurafenib/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"},{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}],"pathway":[{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"term":[{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"}],"paper":[{"id":"paper-tiacci-n-engl-j-med","kind":"paper","name":"BRAF mutations in hairy-cell leukemia","route":"/key-papers/paper-tiacci-n-engl-j-med/"}],"person":[{"id":"sascha-dietrich","kind":"person","name":"Sascha Dietrich","route":"/people/sascha-dietrich/"}],"trial":[{"id":"nct01059786","kind":"trial","name":"Randomized Phase II Trial of Rituximab With Either Pentostatin or Bendamustine for Multiply Relapsed or Refractory Hairy Cell Leukemia","route":"/trials/nct01059786/"}]}}