Hsi Eric D, Jung Sin-Ho, Lai Raymond, Johnson Jeffrey L, Cook James R, Jones Dan, Devos Sven, Cheson Bruce D, Damon Lloyd E, Said Jonathan
Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH 44195, USA.
Leuk Lymphoma. 2008 Nov;49(11):2081-90. doi: 10.1080/10428190802419640.
The proliferation index in mantle cell lymphoma (MCL) has not been validated in the context of aggressive therapy regimens in the rituximab era. We assessed Ki67 and PIM1 (a cell cycle-related gene upregulated in blastoid MCL) expression by immunohistochemistry in a phase II study Cancer and Leukemia Group B 59909 of aggressive chemotherapy and rituximab followed by autologous stem cell transplantation plus rituximab in untreated MCL patients <70 years of age. As a continuous variable or using a cutoff of 35%, higher image analysis (IA Ki67, n = 52) was associated with shorter progression free survival (PFS) (P < or = 0.030) and event free survival (EFS) (P < or = 0.017). PIM1 expression (n = 50) was associated with PFS (P = 0.033) and EFS (P = 0.043). Bivariate Cox models showed IA Ki67 and PIM1 were independent of clinical factors. High Ki67 (>35%) is an important independent prognostic marker in aggressively treated MCL in the rituximab era. PIM1 expression predicts poor outcome and, given its potential role as a therapeutic target, deserves further study.
在利妥昔单抗时代，套细胞淋巴瘤（MCL）的增殖指数在积极治疗方案背景下尚未得到验证。在一项II期研究（癌症与白血病B组59909研究）中，我们通过免疫组织化学评估了年龄<70岁的初治MCL患者在接受积极化疗、利妥昔单抗治疗，随后进行自体干细胞移植加利妥昔单抗治疗时的Ki67和PIM1（在母细胞样MCL中上调的一种细胞周期相关基因）表达情况。作为连续变量或采用35%的临界值时，更高的图像分析结果（IA Ki67，n = 52）与无进展生存期（PFS）缩短（P≤0.0,30）和无事件生存期（EFS）缩短（P≤0.017）相关。PIM1表达（n = 50）与PFS（P = 0.033）和EFS（P = 0.043）相关。双变量Cox模型显示IA Ki67和PIM1与临床因素无关。高Ki67（>35%）是利妥昔单抗时代积极治疗的MCL中一个重要的独立预后标志物。PIM1表达预示预后不良，鉴于其作为治疗靶点的潜在作用，值得进一步研究。
