University of Arizona College of Medicine, 475 N 5th St, HSEB C536, Phoenix, AZ, 85004, USA.
Division of Hematology and Medical Oncology, Mayo Clinic, Phoenix, AZ, USA.
Curr Treat Options Oncol. 2022 Jan;23(1):99-116. doi: 10.1007/s11864-021-00927-z. Epub 2022 Feb 18.
Hairy cell leukemia variant (HCL-V) is a rare B cell lymphoproliferative disorder with a clinical-pathological distinction from the classic form of hairy cell leukemia (HCL-C). HCL-V is more aggressive in nature, has a higher tendency to be refractory to conventional purine analog pharmacotherapies, and leads to a poorer prognosis. Hence, these differing features bring paramount importance to the diagnosis and management of HCL-V. While there is no genetic mutation diagnostic of HCL-V, genetic profiling efforts have identified potential therapeutic targets (i.e., MAP2K1, KDM6A, CREBBP, ARID1A, CCND3, U2AF1, KMT2C) and yielded prognostic markers (i.e., IGHV4-34 rearrangements). To date, combination chemoimmunotherapies, such as cladribine and rituximab, have shown the best results in HCL-V. Future directions include targeted therapies such as moxetumomab pasudotox, ibrutinib, trametinib, and binimetinib and potentially anti-CD22 chimeric antigen receptor T cell therapy. The purpose of this review is to provide an outline of the diagnostic approach and an update on the therapeutic advancements in HCL-V.
多毛细胞白血病变异型（HCL-V）是一种罕见的 B 细胞淋巴增生性疾病，其临床病理学特征与经典型多毛细胞白血病（HCL-C）不同。HCL-V 本质上更具侵袭性，对常规嘌呤类似物药物治疗的耐药性更高，预后更差。因此，这些不同的特征对 HCL-V 的诊断和管理至关重要。虽然目前没有特定的基因突变可诊断 HCL-V，但基因谱分析已确定了潜在的治疗靶点（如 MAP2K1、KDM6A、CREBBP、ARID1A、CCND3、U2AF1、KMT2C）和预后标志物（如 IGHV4-34 重排）。迄今为止，克拉屈滨和利妥昔单抗联合化疗免疫治疗在 HCL-V 中显示出最佳疗效。未来的治疗方向包括靶向治疗，如莫替莫单抗帕苏妥珠单抗、伊布替尼、曲美替尼和比尼替尼，以及潜在的抗 CD22 嵌合抗原受体 T 细胞治疗。本文旨在概述 HCL-V 的诊断方法，并介绍其治疗进展。
