Abstract
Hairy cell leukemia is a rare chronic lymphoproliferative disorder with indolent but progressive clinical course. Patients require treatment when they have significant cytopenia or recurrent infections. The gold standard treatment are purine nucleoside analogues (cladribine and pentostatine), with these agents the rate of complete remission can approach even 95 %. The differential diagnosis between classical hairy cell leukemia and other, rare splenic lymphomas that can mimic this disease might be really challenging. Splenic lymphoma with villous lymphocytes and other new, provisional WHO entities share some, but not all immunophenotypical features with hairy cell leukemia. The correct diagnosis is of an extreme importance as these entities require different treatment. Thus further investigation in the pathogenesis of hairy cell leukemia is required in order to solve this challenge. Discovery of the BRAF V600E mutation as a disease-defining genetic event in hairy cell leukemia can be helpful in both differential diagnosis and treatment of this disease. We report the case of three hairy cell leukemia patients, whose diagnosis or treatment was based on this newly discovered somatic mutation, but the treatment results and side effects were individual.
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References
Grever MA (2010) How I Treat Hairy Cell Leukemia. Blood 115:21–28
Krenács L, Tóth-Lipták J, Demeter J et al (2013) Monoclonal Antibody HBME-1 Reacts with a Minor Subset of B cells with Villous Surface and can be Useful in the Diagnosis of Hairy Cell Leukemia and other Indolent Lymphoproliferations of Villous B Lymphocytes. Virchows Arch 463(6):787–794
Naik RR, Saven A (2012) My Treatment Approach to Hairy Cell Leukemia. Mayo Clin Proc 87(1):67–76
Tiacci E, Trifonov V, Schiavoni G et al (2011) BRAF Mutations in Hairy Cell Leukemia. N Engl J Med 364:2305–2315
Davies H, Bignell GR, Cox C et al (2002) Mutations of the BRAF Gene in Human Cancer. Nature 417:949–954
Tiacci E, Schiavoni G, Forconi F et al (2012) Simple Genetic Diagnosis of Hairy cell Leukemia by Sensitive Detection of the BRAF-V600E Mutation. Blood 119:192–195
Blombery PA, Wong SQ, Hewitt CA et al (2012) Detection of BRAF Mutations in Patients with Hairy Cell Leukemia and Related Lymphoproliferative Disorders. Haematologica 97:780–783
Boyd EM, Bench AJ, Veer MB V’t et al (2011) High Resolution Melting Analysis for Detection of BRAF exon 15 Mutations in Hairy Cell Leukaemia and Other Lymphoid Malignancies. Br J Haem 155:609–612
Arcaini L, Zibellini S, Boveri E et al (2012) The BRAF V600E Mutation in Hairy Cell Leukemia and other Mature B-cell Neoplasms. Blood 119:188–191
Lennerz JK, Klaus BM, Marienfeld RB et al (2012) Pyrosequencing of BRAF V600E in Routine Samples of Hairy Cell Leukaemia Identifies CD5+ variant Hairy Cell Leukaemia that Lacks V600E. Br J Haem 157:267–269
Schnittger S, Bacher U, Haferlach T et al (2012) Development and Validation of a Real-Time Quantification Assay to Detect and Monitor BRAFV600E Mutations in Hairy Cell Leukemia. Blood 119:3151–3154
Xi L, Arons E, Navarro W et al (2012) Both variant and IGHV4-34-Expressing Hairy Cell Leukemia Lack the BRAF V600E Mutation. Blood 119:3330–3332
Langabeer SE, O’Brien D, Liptrot S et al (2012) Correlation of the BRAF V600E Mutation in Hairy Cell Leukaemia with Morphology, Cytochemistry and Immunophenotype. Int J Lab Hem 34:417–421
Andrulis M, Penzel R, Weichert W et al (2012) Application of a BRAF V600E Mutation-Specific Antibody for the Diagnosis of Hairy Cell Leukemia. Am J SurgPathol 36(12):1796–1800
Laurini JA, Aoun P, Iqbaal J et al (2012) Investigation of the BRAF V600E Mutation by Pyrosequencing in Lymphoproliferative Disorders. Am J Clin Pathol 138:877–883
Dietrich S, Glimm H, Andrulis M et al (2012) BRAF Inhibition in Refractory Hairy-Cell Leukemia. N Engl J Med 366:2038–2040
Follows GA, Sims H, Bloxham DM et al (2013) Rapid Response of Biallelic BRAF V600E Mutated Hairy Cell Leukemia to Low Dose Vemurafenib. Br J Haem 161(1):150–153
Peyrade F, Ré D, Ginet C et al (2013) Low-Dose Vemurafenib Induces Complete Remission in a Case of Hairy-Cell Leukemia with a V600E Mutation. Haematologica 98(2):e20–e22
Munoz J, Schlette E, Kurzrock R (2013) Rapid Response to Vemurafenib in a Heavily Pretreated Patient with Hairy Cell Leukemia and a BRAF Mutation. J Clin Oncol 31(20):e351–e352
Maurer H, Haas P, Wengenmayer T et al (2013) Successful Vemurafenib Salvage Treatment in a Patient with Primary Refractory Hairy Cell Leukemia and Pulmonary Aspergillosis. Ann Hematol DOI. doi:10.1007/s.00277–013–1987–7
Urnova EC, Al-Radi LS, Kuzmina LA et al (2013) Successful use of Vemurafenib in a Patient with a Resistant Hairy Cell Leukemia. Ter Arkh 85(7):76–78
Samuel J, Macip S, Dyer MJS (2014) Efficacy of Vemurafenib in Hairy-Cell Leukemia. N Engl J Med 370:286–288
Dietrich S, Hüllein J, Hundemer M et al (2013) Continued Response off Treatment after BRAF Inhibition in Refractory Hairy Cell Leukemia. J Clin Oncol 31(19):e300–e303
Cantwell-Dorris ER, O’Leary JJ, Sheils OM (2011) BRAF V600E: Implications for Carcinogenesis and Molecular Therapy. Mol Canc Ther 3:385–394
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Sári, E., Nagy, Z.G., Baghy, K. et al. Treatment of Refractory Hairy Cell Leukemia with a BRAF-inhibitor: Lessons to be Learnt. Pathol. Oncol. Res. 20, 973–980 (2014). https://doi.org/10.1007/s12253-014-9783-9
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DOI: https://doi.org/10.1007/s12253-014-9783-9