Detection of MRD may predict the outcome of patients with Philadelphia chromosome-positive ALL treated with tyrosine kinase inhibitors plus chemotherapy
Detection of MRD may predict the outcome of patients with Philadelphia chromosome-positive ALL treated with tyrosine kinase inhibitors plus chemotherapy
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DOI：
10.1182/blood-2012-11-466482
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发表时间：
2013-08-15
期刊：
影响因子：
20.3
通讯作者：
Kantarjian, Hagop M.
中科院分区：
文献类型：
--
作者：
Ravandi, Farhad;Jorgensen, Jeffrey L.;Kantarjian, Hagop M.
2001年至2011年，对122例初治费城染色体阳性急性淋巴细胞白血病患者采用化疗+伊马替尼（n = 54）或化疗+达沙替尼（n = 568）方案进行治疗。115例（94%）患者达到完全缓解（CR），包括101例仅接受1个诱导疗程且至少有+微小残留病（MRD）评估的患者; 25例患者在首次CR时接受了异基因干细胞移植，并被排除，剩下76例患者作为本报告的受试者。在诱导结束时和此后类似的3个月间隔，通过多参数流式细胞术（MFC）和实时定量聚合酶链反应（PCR）进行MRD监测。中位年龄为54岁（范围：21-84岁）。在达到CR时达到至少一个主要分子学缓解（MMR; BCR-ABL/ABL < 0.1%）的患者生存率无差异（P = 0.22）。在3、6、9和12个月达到MMR的患者生存率更高（P分别为0.02、0.04、0.05和0.01）。CR时MFC阴性不能预测生存率的改善（P =.2）。在3个月和12个月时，MFC阴性MRD与生存率改善相关（P = 0.04和0.001）。通过PCR和MFC监测MRD可识别在首次CR中从强化治疗中获益的患者。
From 2001 to 2011, 122 patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia were treated with chemotherapy + imatinib (n = 54) or + dasatinib (n 5 68). One hundred fifteen (94%) achieved complete remission (CR) including 101 patients who achieved it with only 1 induction course and had at least + minimal residual disease (MRD) assessment; 25 patients underwent an allogeneic stemcell transplant in first CR and were excluded, leaving 76 patients as the subject of this report. MRDmonitoring by multiparameter flow cytometry (MFC) and real-time quantitative polymerase chain reaction (PCR) was performed at the end of induction and at similar to 3-month intervals thereafter. Median age was 54 years (range, 21-84 years). There was no difference in survival by achievement of at least amajor molecular response (MMR; BCR-ABL/ABL < 0.1%) at CR (P =.22). Patients achieving MMR at 3, 6, 9, and 12 months had a better survival (P =.02,.04,.05, and.01, respectively). Negative MFC at CR did not predict for improved survival (P =.2). At 3 and 12 months, negative MRD by MFC was associated with improved survival (P =.04 and .001). MRD monitoring by PCR and MFC identifies patients who benefit from treatment intensification in first CR.