Rai K R, Döhner H, Keating M J, Montserrat E
Division of Hematology-Oncilogy, Long Island Jewish Medical Center, New Hyde Park, NY 11040, USA.
Hematology Am Soc Hematol Educ Program. 2001:140-56. doi: 10.1182/asheducation-2001.1.140.
Drs. Hartmut Döhner, Michael J. Keating, Kanti R. Rai and Emili Montserrat form the panel to review chronic lymphocytic leukemia (CLL) while focusing on the clinical features of a particular patient. The pace of progress in CLL has accelerated in the past decade. The pathophysiological nature of this disease, as had been known in the past, was based largely on the intuitive and empiric notions of two leaders in hematology, William Dameshek and David Galton. Now the works of a new generation of leaders are providing us with the scientific explanations of why CLL is a heterogeneous disease, perhaps consisting of at least two separate entities. In one form of CLL, the leukemic lymphocytes have a surface immunoglobulin (Ig) variable region gene that has undergone somatic mutations, with tell-tale markers suggesting that these cells had previously traversed the germinal centers. Such patients have a distinctly superior prognosis than their counterparts whose leukemic lymphocytes IgV genes have no mutations (these are indeed immunologically naive cells), who have a worse prognosis. The introduction of fluorescence in situ hybridization (FISH) technique has provided us with new insights into the diverse chromosomal abnormalities that can occur in CLL, and which have significant impact on the clinical behavior and prognosis of patients with this disease. Major advances in therapeutics of CLL also have occurred during the past decade. Two monoclonal antibodies, Campath-1H (anti-CD52) and rituximab (anti-CD20), and one nucleoside analogue, fludarabine, have emerged as three agents of most promise in the front-line treatment of this disease. Studies currently in progress reflect our attempts to find the most effective manner of combining these agents to improve the overall survival statistics for CLL patients. As in many other hematological malignancies, high dose chemotherapy followed by autologous or HLA-compatible allogeneic stem cells rescue strategies are under study as a salvage treatment for a relatively younger age group of CLL patients with poor prognosis characteristics.
哈特穆特·德赫纳博士、迈克尔·J·基廷博士、坎蒂·R·拉伊博士和埃米利·蒙特塞拉特博士组成了该小组，在聚焦一位特定患者临床特征的同时对慢性淋巴细胞白血病（CLL）进行回顾。在过去十年中，CLL的进展速度加快。过去已知这种疾病的病理生理本质很大程度上基于血液学领域两位领军人物威廉·达梅谢克和大卫·高尔顿直观的经验性概念。现在，新一代领军人物的研究成果正在为我们提供科学解释，说明为什么CLL是一种异质性疾病，可能至少由两个不同实体组成。在一种形式的CLL中，白血病淋巴细胞具有一个经历了体细胞突变的表面免疫球蛋白（Ig）可变区基因，有明显的标记表明这些细胞此前曾穿过生发中心。这类患者的预后明显优于白血病淋巴细胞IgV基因未发生突变的患者（这些细胞确实是免疫未成熟细胞），后者预后较差。荧光原位杂交（FISH）技术的引入为我们提供了关于CLL中可能出现的多种染色体异常的新见解，这些异常对该疾病患者的临床行为和预后有重大影响。在过去十年中，CLL治疗方面也取得了重大进展。两种单克隆抗体，Campath - 1H（抗CD52）和利妥昔单抗（抗CD20），以及一种核苷类似物氟达拉滨，已成为该疾病一线治疗中最有前景的三种药物。目前正在进行的研究反映了我们试图找到最有效的联合使用这些药物的方式，以改善CLL患者的总体生存统计数据。与许多其他血液系统恶性肿瘤一样，高剂量化疗后进行自体或HLA匹配的异基因干细胞挽救策略正在作为一种挽救治疗方法，用于治疗预后特征较差的相对年轻的CLL患者群体。
