Haemato-Oncology Department, Royal Marsden Hospital & Institute of Cancer Research, 203 Fulham road, London SW3 6JJ, England.
Curr Cancer Drug Targets. 2012 Jun;12(5):484-504. doi: 10.2174/156800912800673211.
Rarer chronic lymphoid leukaemias represent a challenge to the clinicians due to the limited information on their pathogenesis, difficulties on setting up prospective clinical trials and to their refractoriness to drugs used in the most common form of chronic lymphocytic leukaemia (CLL). In this review all these issues are addressed in three B-cell leukaemias: B-cell prolymphocytic leukaemia (B-PLL), hairy cell leukaemia (HCL) and HCL-variant and three T-cell leukaemias: T-cell prolymphocytic leukaemia (T-PLL), T-cell large granular lymphocytic leukaemia (T-cell LGLL) and adult T-cell leukaemia lymphoma (ATLL). Data will be presented on the natural history, current therapies and emerging drugs potentially useful in the treatment of patients with these leukaemias. Emphasis is made on: 1- the novel agents targeting a variety of B and T-cell antigens expressed on the surface of the leukaemic cells; these are either unconjugated monoclonal antibodies (McAb) such as Rituximab (anti-CD20), the second and third generation of anti-CD20 McAbs, Alemtuzumab (anti-CD52), Siplizumab (anti-CD2), Daclizumab (anti-CD25) and KW-0761, an anti-chemokine receptor 4 (CCR4) or McAbs conjugated to toxins such as CD22 linked to the pseudomonas exotoxin or radiolabelled McAb; 2- the use of new purine nucleosides such as nelarabine and 3- agents targeting deregulated genes in the leukaemic cells from these diseases such as the Poly (ADP-ribose) polymerase (PARP) Olarapib in T-PLL with deregulation of the ataxia telangiectasia mutated (ATM) gene. Data of phase I and II clinical studies with these agents as well as the potential and current use of other drugs are outlined.
罕见的慢性淋巴细胞白血病对临床医生来说是一个挑战，因为它们的发病机制信息有限，难以进行前瞻性临床试验，并且对最常见的慢性淋巴细胞白血病（CLL）形式的药物具有耐药性。在这篇综述中，我们将讨论三种 B 细胞白血病：B 前淋巴细胞白血病（B-PLL）、毛细胞白血病（HCL）和 HCL 变体，以及三种 T 细胞白血病：T 前淋巴细胞白血病（T-PLL）、T 细胞大颗粒淋巴细胞白血病（T-cell LGLL）和成人 T 细胞白血病淋巴瘤（ATLL）。我们将介绍这些白血病的自然史、当前治疗方法和新兴药物，这些药物可能对治疗这些患者有用。重点介绍：1- 针对白血病细胞表面表达的各种 B 和 T 细胞抗原的新型靶向药物；这些药物要么是未偶联的单克隆抗体（McAb），如利妥昔单抗（抗-CD20）、第二代和第三代抗-CD20 McAb、阿仑单抗（抗-CD52）、西利珠单抗（抗-CD2）、达珠单抗（抗-CD25）和 KW-0761，一种抗趋化因子受体 4（CCR4）的 McAb，要么是与假单胞菌外毒素偶联的 McAb，或放射性标记的 McAb；2- 新型嘌呤核苷，如奈拉滨；3- 针对这些疾病白血病细胞中失调基因的药物，如 T-PLL 中失调的共济失调毛细血管扩张突变基因（ATM）的聚（ADP-核糖）聚合酶（PARP）奥拉帕尼。概述了这些药物的 I 期和 II 期临床试验数据以及其他药物的潜在和当前用途。
