Pemmaraju Naveen, Kantarjian Hagop, Jorgensen Jeffrey L, Jabbour Elias, Jain Nitin, Thomas Deborah, O'Brien Susan, Wang Xuemei, Huang Xuelin, Wang Sa A, Konopleva Marina, Konoplev Sergej, Kadia Tapan, Garris Rebecca, Pierce Sherry, Garcia-Manero Guillermo, Cortes Jorge, Ravandi Farhad
Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas.
Department of Pathology, University of Texas, MD Anderson Cancer Center, Houston, Texas.
Am J Hematol. 2017 Mar;92(3):279-285. doi: 10.1002/ajh.24629. Epub 2017 Feb 1.
We sought to determine the significance of minimal residual disease (MRD) relapse in patients with ALL after achieving MRD negative status following induction and consolidation therapy. Between January 2003 and September 2014, 647 newly diagnosed patients were treated [HyperCVAD-based (n = 531); Augmented BFM (n = 116)]. Six hundred and one (93%) achieved complete remission (CR), and 546 (91%) became MRD negative. Fifty-five patients [HyperCVAD-based (n = 49); Augmented BFM (n = 6)] developed recurrence of MRD while still in morphological CR and are the subjects of this study. MRD was assessed by 6-color (4-color prior to 2009) multi-parameter flow cytometry (MFC) at CR and multiple time points thereafter. Their median age was 44 years (range, 18-72 years), median WBC at initial presentation was 7.3 K/µL (range, 0.6-303.8 K/µL ) and median bone marrow blast percentage 88% (range, 26-98%). The median time to MRD relapse was 14 months (range 3-58 months). Forty-four (80%) patients subsequently developed morphological relapse after median of 3 months (range, <1-33 months) from detection of MRD recurrence. Treatments received after MRD positivity and prior to morphological relapse: 16 continued maintenance chemotherapy; 15 received late intensification; 9 allogeneic stem cell transplant, 9 changed chemotherapy, 6 no further therapy. Only six remain alive and in CR1 and nine are alive after morphological relapse. MRD relapse detected by MFC at any time after achieving CR is associated with a high risk for morphological relapse. SCT can result in long-term remission in some patients. Prospective studies of long-term MRD assessments, together with less toxic treatment strategies to eradicate MRD, are warranted.
我们试图确定急性淋巴细胞白血病（ALL）患者在诱导和巩固治疗后达到微小残留病（MRD）阴性状态后MRD复发的意义。2003年1月至2014年9月期间，647例新诊断患者接受了治疗[基于HyperCVAD方案（n = 531）；强化BFM方案（n = 116）]。601例（93%）达到完全缓解（CR），546例（91%）MRD转为阴性。55例患者[基于HyperCVAD方案（n = 49）；强化BFM方案（n = 6）]在仍处于形态学CR时出现MRD复发，这些患者是本研究的对象。在CR时及之后的多个时间点，通过6色（2009年之前为4色）多参数流式细胞术（MFC）评估MRD。他们的中位年龄为44岁（范围18 - 72岁），初诊时中位白细胞计数为7.3 K/µL（范围0.6 - 303.8 K/µL），中位骨髓原始细胞百分比为88%（范围26 - 98%）。MRD复发的中位时间为14个月（范围3 - 58个月）。44例（80%）患者在检测到MRD复发后中位3个月（范围<1 - 33个月）随后出现形态学复发。MRD阳性至形态学复发前接受的治疗：16例继续维持化疗；15例接受晚期强化治疗；9例接受异基因干细胞移植，9例更换化疗方案，6例未进一步治疗。仅6例仍存活且处于CR1，9例在形态学复发后存活。CR后任何时间通过MFC检测到的MRD复发与形态学复发的高风险相关。异基因造血干细胞移植（SCT）可使部分患者获得长期缓解。有必要对长期MRD评估进行前瞻性研究，并采用毒性较小的治疗策略来根除MRD。
