University of Chicago Medical Center 5841, S. Maryland Ave, MC2115 Chicago, IL 60637, USA.
Haematologica. 2012 Apr;97(4):579-85. doi: 10.3324/haematol.2011.050203. Epub 2011 Nov 18.
In the present study, the prognostic impact of minimal residual disease during treatment on time to progression and overall survival was analyzed prospectively in patients with mantle cell lymphoma treated on the Cancer and Leukemia Group B 59909 clinical trial.
Peripheral blood and bone marrow samples were collected during different phases of the Cancer and Leukemia Group B 59909 study for minimal residual disease analysis. Minimal residual disease status was determined by quantitative polymerase chain reaction of IgH and/or BCL-1/JH gene rearrangement. Correlation of minimal residual disease status with time to progression and overall survival was determined. In multivariable analysis, minimal residual disease, and other risk factors were correlated with time to progression.
Thirty-nine patients had evaluable, sequential peripheral blood and bone marrow samples for minimal residual disease analysis. Using peripheral blood monitoring, 18 of 39 (46%) achieved molecular remission following induction therapy. The molecular remission rate increased from 46 to 74% after one course of intensification therapy. Twelve of 21 minimal residual disease positive patients (57%) progressed within three years of follow up compared to 4 of 18 (22%) molecular remission patients (P=0.049). Detection of minimal residual disease following induction therapy predicted disease progression with a hazard ratio of 3.7 (P=0.016). The 3-year probability of time to progression among those who were in molecular remission after induction chemotherapy was 82% compared to 48% in patients with detectable minimal residual disease. The prediction of time to progression by post-induction minimal residual disease was independent of other prognostic factors in multivariable analysis.
Detection of minimal residual disease following induction immunochemotherapy was an independent predictor of time to progression following immunochemotherapy and autologous stem cell transplantation for mantle cell lymphoma.
在本研究中,我们前瞻性地分析了在癌症和白血病组 B59909 临床试验中接受治疗的套细胞淋巴瘤患者的治疗期间微小残留病对进展时间和总生存期的预后影响。
在癌症和白血病组 B59909 研究的不同阶段采集外周血和骨髓样本进行微小残留病分析。通过定量聚合酶链反应检测 IgH 和/或 BCL-1/JH 基因重排来确定微小残留病状态。确定微小残留病状态与进展时间和总生存期的相关性。在多变量分析中,将微小残留病和其他危险因素与进展时间相关联。
39 例患者有可评估的、连续的外周血和骨髓样本进行微小残留病分析。使用外周血监测,39 例患者中有 18 例(46%)在诱导治疗后达到分子缓解。强化治疗一个疗程后,分子缓解率从 46%增加到 74%。在 21 例微小残留病阳性患者中,有 12 例(57%)在随访 3 年内进展,而在 18 例分子缓解患者中,有 4 例(22%)进展(P=0.049)。诱导治疗后检测到微小残留病与疾病进展的风险比为 3.7(P=0.016)。在诱导化疗后达到分子缓解的患者中,3 年进展时间的概率为 82%,而在可检测到微小残留病的患者中为 48%。多变量分析中,诱导后微小残留病对进展时间的预测独立于其他预后因素。
在接受免疫化学治疗和自体干细胞移植治疗套细胞淋巴瘤后,诱导免疫化疗后检测到微小残留病是进展时间的独立预测因素。