Successful treatment of hairy cell leukemia with TP53 abnormality using cladribine combined with low-dose rituximab: a case report and literature review.

Hairy Cell Leukemia Variant Has Similar Survival to Classical Disease Despite Poorer Responses to Initial Therapy: A 30-Year Experience from Memorial Sloan Kettering Cancer Center

Presence and Absence of the BRAF V600E Mutation in Hairy Cell Leukemia and Its Variants

Evaluation of BRAFV600E, NRAS and KRAS Mutations As Well As IGHV Usage for Diagnostic Use in Hairy Cell Leukemia, Hairy Cell Leukemia-Variant and Splenic Marginal Zone Lymphoma.

Transcriptomic and Epigenomic Landscape of Hairy Cell Leukemia at Single-Cell Resolution

Increased Expression of Myc in Hairy Cell Leukemia, and Cell-Sensitivity to JQ1

CLL-358: First-Line Treatment of Hairy Cell Leukemia with Cladribine Followed by Rituximab Consolidation Significantly Improves Leukemia-Free Survival

Genomic Analysis of Hairy Cell Leukemia Identifies Novel Recurrent Genetic Alterations

Infection at the Time of Initial Therapy for Hairy Cell Leukemia Is Associated with Inferior Time to Next Treatment

Despite its rarity, hairy cell leukemia (HCL) remains a fascinating disease and the physiopathology is becoming more and more understood. The accurate diagnosis of HCL relies on the recognition of hairy cells by morphology and flow cytometry (FCM) in the blood and/or bone marrow (BM). The BRAF V600E mutation, an HCL-defining mutation, represents a novel diagnostic parameter and a potential therapeutic target. The precise cellular origin of HCL is a late-activated postgerminal center memory B cell. BRAF mutations were detected in hematopoietic stem cells (HSCs) of patients with HCL, suggesting that this is an early HCL-defining event. Watch-and-wait strategy is necessary in approximately 10% of asymptomatic HCL patients, sometimes for several years. Purine analogs (PNAs) are the established first-line options for symptomatic HCL patients. In second-line treatment, chemoimmunotherapy combining PNA plus rituximab should be considered in high-risk HCL patients. The three options for relapsed/refractory HCL patients include recombinant immunoconjugates targeting CD22, BRAF inhibitors, and BCR inhibitors. The clinical interest to investigate blood minimal residual disease (MRD) was recently demonstrated, with a high risk of relapse in patients with positive testing for MRD and a low risk in patients with negative testing. However, efforts must be made to standardize MRD analyses in the near future. Patients with HCL are at risk of second malignancies. The increased risk could be related to the disease and/or the treatment, and the respective role of PNAs in the development of secondary malignancies remains a topic of debate.

Herein, we describe the clinicopathologic and genetic characteristics of the first report of simultaneous bone marrow involvement by classical hairy cell leukemia (HCL) and leukemic non-nodal variant of mantle cell lymphoma (L-NN-MCL) with t(11;14)(q13;q32) with BRAF mutation and deletion of TP53. A 40-year-old asymptomatic man was investigated for incidental neutropenia and thrombocytopenia. Flow cytometry showed two distinct monotypic B-cell populations: one expressed CD19 (bright), CD20 (bright), FMC7, CD103, CD25, CD11c, CD123, and IgD (bright) and showed kappa light chain restriction (bright), consistent with HCL and the other kappa-restricted CD5/CD10-negative B-cell population with distinctive immunophenotypic features. The bone marrow biopsy is infiltrated by an abnormal B-lymphoid infiltrate with different patterns of infiltration in different marrow areas. Fluorescence in situ hybridization (FISH) analysis revealed a CCND1/IGH rearrangement, t(11;14)(q13;q32), and deletion of TP53. The BRAF V600E missense mutation was detected by quantitative real-time polymerase chain reaction (PCR). The diagnosis of a composite B-cell neoplasm was composed of HCL together with a second CD5/CD10-negative monotypic B-cell population, with CCND1/IGH fusion, favoring the 2016 WHO new category of L-NN-MCL (CD5/SOX11-negative). Treatment with cladribine and rituximab normalized the blood counts within 6 weeks without significant side effects. L-NN-MCL is one of the smoldering MCL subtypes, recently listed in WHO 2016 as a separate variant, with a particular set of unique features and a less aggressive clinical course compared to classical MCL. To date, the clinicopathological features (including the bone marrow findings) of L-NN-MCL have not been sufficiently characterized in the literature. We describe the first report of synchronous presentation of HCL and L-NN-MCL. This case represents a real challenge from the biologic, diagnostic and therapeutic point of views, due to extremely rare combination of two distinct uncommon B-cell neoplasms. The study of composite lymphomas offers the opportunity to evaluate the etiology and the clonal interrelationship involved in the pathogenesis/evolution of lymphomas.

First Line Chemo-Free Therapy with the BRAF Inhibitor Vemurafenib Combined with Obinutuzumab Is Effective in Patients with Hcl

Simple SummaryStandard treatment with purine analogues facilitates a near normal life expectancy in the majority of patients with classic hairy cell leukemia (HCL), a rare chronic B-cell malignancy. However, nearly all patients ultimately relapse and require retreatment, while drug-induced myelotoxicity accumulates predisposing to infectious complications and, possibly, secondary malignancies. Persistence of minimal residual disease (MRD) in a substantial portion of treated patients has become a surrogate for this still limited treatment efficacy. New insights into disease biology initiated design and investigation of several new, chemotherapy-free, targeted drugs with encouraging efficacy in early clinical trials aimed at enhancing eradication of MRD and optimizing drug tolerability. This review provides an update on recent clinical trials investigating treatment strategies beyond purine analogues in HCL and discusses clinically relevant obstacles still to overcome.Classic hairy cell leukemia (HCL) is a rare indolent B-cell lymphoproliferative disorder characterized by profound pancytopenia and frequent infectious complications due to progressive infiltration of the bone marrow and spleen. Lacking effective treatment options, affected patients were confronted with a dismal survival prognosis of less than 5 years when the disease was first described in 1958. Tremendous therapeutic advances were accomplished with the introduction of purine analogues such as cladribine in the 1990s, facilitating a near-normal life expectancy in most HCL patients. Nevertheless, nearly all patients eventually relapse and require successive retreatments, while drug-associated myelotoxicity may accumulate and secondary malignancies may evolve. Detection of minimal residual disease (MRD) in a substantial portion of treated patients has become a surrogate for this still limited treatment efficacy. In the last decade, novel biologic insights such as identification of the driver mutation BRAF V600E have initiated the development and clinical investigation of new, chemotherapy-free, targeted drugs in HCL treatment, with encouraging efficacy in early clinical trials aimed at boosting eradication of MRD while optimizing drug tolerability. This review summarizes current clinical trials investigating treatment strategies beyond purine analogues in HCL and discusses clinically relevant obstacles still to overcome.

Classical hairy cell leukemia (HCL-c) and HCL variant (HCL-v) are recognized as separate entities with HCL-v having significantly shorter overall survival. Proteomic studies, shown to be prognostic in various forms of leukemia, have not been performed in HCL. We performed reverse phase protein array-based protein profiling with 384 antibodies in HCL-c (n = 12), HCL-v (n = 4), and normal B-cells (n = 5) samples. While HCL could be distinguished from normal based on unsupervised hierarchical clustering, overlap in protein expression patterns was seen between HCL-c and HCL-v, with ∼10% of the proteins being differentially expressed, suggesting potential therapeutic targets.

Sang-Yong Shin, M.D., Seung-Tae Lee, M.D., Hee-Jin Kim, M.D., Chang-Seok Ki, M.D., Chul Won Jung, M.D.,<br> Jong-Won Kim, M.D., and Sun-Hee Kim, M.D.. Ann Lab Med 2015;35:257-9. https://doi.org/10.3343/alm.2015.35.2.257

Hairy Cell Leukemia: Treatment Successes in the Past 25 Years