Zhou Jianbiao, Goldwasser Meredith A, Li Aihong, Dahlberg Suzanne E, Neuberg Donna, Wang Hongjun, Dalton Virginia, McBride Kathryn D, Sallan Stephen E, Silverman Lewis B, Gribben John G
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Blood. 2007 Sep 1;110(5):1607-11. doi: 10.1182/blood-2006-09-045369. Epub 2007 May 7.
In a prospective trial in 284 children with B-lineage acute lymphoblastic leukemia (ALL), we assessed the clinical utility of real-time quantitative polymerase chain reaction analysis of antigen receptor gene rearrangements for detection of minimal residual disease (MRD) to identify children at high risk of relapse. At the end of induction therapy, the 5-year risk of relapse was 5% in 176 children with no detectable MRD and 44% in 108 children with detectable MRD (P < .001), with a linear association of the level of MRD and subsequent relapse. Recursive partitioning and clinical characteristics identified that the optimal cutoff level of MRD to predict outcome was 10(-3). The 5-year risk of relapse was 12% for children with MRD less than one leukemia cell per 10(3) normal cells (low MRD) but 72% for children with MRD levels greater than this level (high MRD) (P < .001) and children with high MRD had a 10.5-fold greater risk of relapse. Based upon these results we have altered our treatment regimen for children with B-lineage ALL and children with MRD levels greater than or equal to 10(-3) at the end of 4 weeks of multiagent induction chemotherapy now receive intensified treatment to attempt to decrease their risk of subsequent relapse.
在一项针对284例B系急性淋巴细胞白血病（ALL）患儿的前瞻性试验中，我们评估了抗原受体基因重排的实时定量聚合酶链反应分析用于检测微小残留病（MRD）以识别复发高危患儿的临床实用性。诱导治疗结束时，176例未检测到MRD的患儿5年复发风险为5%，而108例检测到MRD的患儿5年复发风险为44%（P <.001），MRD水平与随后的复发呈线性相关。递归划分和临床特征表明，预测预后的MRD最佳临界值为10^(-3)。每10^3个正常细胞中MRD低于一个白血病细胞的患儿（低MRD）5年复发风险为12%，但MRD水平高于此水平的患儿（高MRD）5年复发风险为72%（P <.001），高MRD患儿的复发风险高10.5倍。基于这些结果，我们改变了B系ALL患儿的治疗方案，多药诱导化疗4周结束时MRD水平大于或等于10^(-3)的患儿现在接受强化治疗，以试图降低其随后复发的风险。
