Maloum Karim, Settegrana Catherine, Chapiro Elise, Cazin Bruno, Leprêtre Stéphane, Delmer Alain, Leporrier Michel, Dreyfus Brigitte, Tournilhac Olivier, Mahe Beatrice, Nguyen-Khac Florence, Lesty Claude, Davi Frederic, Merle-Béral Hélène
Service d'Hématologie Biologique, CHU Pitié-Salpêtrière, Paris, France.
Ann Hematol. 2009 Dec;88(12):1215-21. doi: 10.1007/s00277-009-0742-6. Epub 2009 Apr 2.
Several prognostic factors can predict the rapid progression in chronic lymphocytic leukaemia (CLL), including IGHV mutational status, cytogenetic abnormalities and, more recently, LPL/ADAM29 expression. In contrast, few studies have been devoted to the influence of these factors on clinical outcome in responding patients after therapy. We here propose to analyse the impact of IGHV gene status, LPL and ADAM29 gene expression on disease-free survival (DFS) and overall survival (OS) in 41 stage B or C CLL patients in remission after oral fludarabine plus cyclophosphamide. The median follow-up was of 64 (16-74) months. Sequencing of IGHV showed mutated (M) VH genes in 16 of 41 cases and unmutated (UM) in 25 cases. Analysis of LPL and ADAM29 expression in 35 of 41 cases showed overexpression of ADAM29 in 17 cases (14 M and three UM) and LPL in 18 cases (all UM). Patients expressing UM IGHV and LPL had shorter DFS and OS when compared to patients expressing M IGHV and/or ADAM29. Furthermore, blood minimal residual disease (MRD) evaluation using four-colour flow cytometry was performed in 33 out the 41 patients. We showed that patients who achieved phenotypic remission displayed longer DFS than those with MRD(+). Our results support the use of LPL and ADAM29 gene expression associated to IGHV mutational status for predicting the clinical outcome of patients treated by oral fludarabine + cyclophosphamide and could be considered for treatment strategies.
多种预后因素可预测慢性淋巴细胞白血病（CLL）的快速进展，包括IGHV突变状态、细胞遗传学异常，以及最近发现的LPL/ADAM29表达。相比之下，很少有研究关注这些因素对治疗后缓解患者临床结局的影响。我们在此提议分析IGHV基因状态、LPL和ADAM29基因表达对41例口服氟达拉滨加环磷酰胺后处于缓解期的B或C期CLL患者无病生存期（DFS）和总生存期（OS）的影响。中位随访时间为64（16 - 74）个月。IGHV测序显示，41例中有16例VH基因发生突变（M），25例未发生突变（UM）。对41例中的35例进行LPL和ADAM29表达分析，结果显示17例（14例M和3例UM）ADAM29过表达，18例（均为UM）LPL过表达。与表达M IGHV和/或ADAM29的患者相比，表达UM IGHV和LPL的患者DFS和OS更短。此外，对41例患者中的33例进行了四色流式细胞术血液微小残留病（MRD）评估。我们发现达到表型缓解的患者DFS长于MRD（+）患者。我们的结果支持将与IGHV突变状态相关的LPL和ADAM29基因表达用于预测口服氟达拉滨 + 环磷酰胺治疗患者的临床结局，并可考虑用于治疗策略。
