title: Novel therapeutic options for relapsed hairy cell leukemia.
abstract: The majority of patients with hairy cell leukemia (HCL) achieve a response to therapy with cladribine or pentostatin with or without rituximab. However, late relapses can occur. Treatment of relapsed HCL can be difficult due to a poor tolerance to chemotherapy, increased risk of infections and decreased responsiveness to chemotherapy. The identification of BRAFV600E mutations and the role of aberrant MEK kinase and Bruton's tyrosine kinase (BTK) pathways in the pathogenesis of HCL have helped to develop novel targeted therapies for these patients. Currently, the most promising therapeutic strategies for relapsed or refractory HCL include recombinant immunoconjugates targeting CD22 (e.g. moxetumomab pasudotox), BRAF inhibitors such as vemurafenib and B cell receptor signaling kinase inhibitors such as ibrutinib. Furthermore, the VH4-34 molecular variant of classic HCL has been identified to be less responsive to chemotherapy. Herein, we review the results of the ongoing clinical trials and potential future therapies for relapsed/refractory HCL.
authors.affiliation: a Department of Leukemia , University of Texas M. D. Anderson Cancer Center , Houston , TX , USA.
authors.forename: Preetesh
authors.initials: P
authors.lastname: Jain
authors.affiliation: b Department of Hematology , Hadassah University Hospital, Hebrew University Medical School , Jerusalem , Israel.
authors.forename: Aaron
authors.initials: A
authors.lastname: Polliack
authors.affiliation: a Department of Leukemia , University of Texas M. D. Anderson Cancer Center , Houston , TX , USA.
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D003131:Combined Modality Therapy; D006801:Humans; D007943:Leukemia, Hairy Cell / Q000209:etiology / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D012008:Recurrence; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011947:Receptors, Antigen, B-Cell; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF mutations; HCL; cladribine; hairy cell leukemia; ibrutinib; immunotoxins; pentostatin; rituximab; vemurafenib