Hairy cell leukemia (HCL) and HCL-like disorders: present, emergent treatment options and future directions.

Introduction: Hairy cell leukemia accounts for less than 2% of leukemias. The hairy cells express CD11c, CD25, CD103, and CD123 markers. The BRAF^V600E mutation was detected in 95% of HCL cases. Patients achieve high complete response rate with purine analogues with or without rituximab, but relapses are inevitable. HCL-like disorders including HCL variant, splenic diffuse red pulp lymphoma, and splenic marginal zone lymphoma are BRAF^V600E negative. The CD25 expression is negative. The absence of BRAF^V600E mutation in HCL variant contrasts with the presence of mitogen-activated protein kinase kinase 1 (MAP2K1) mutations in 50% of cases.

Areas covered: We investigated the criteria used to distinguish HCL from HCL-like disorders. Recent discoveries in molecular biology have enabled the introduction of several new drugs in HCL patients. We explore the investigational agents: inhibitors of BRAF, MEK, and Bruton tyrosine kinase and potential future strategies we will use in the future in patients with relapsed/refractory HCL. We also discuss the clinical trials in progress.

Expert opinion: The association of Cladribine (CDA) with rituximab (R) is the standard first-line treatment in fit HCL and HCL variant patients. BRAF and BTK inhibitors are options in relapsed/refractory HCL patients. The optimal treatment sequences remain to be determined.