Zhou Y, Othus M, Araki D, Wood B L, Radich J P, Halpern A B, Mielcarek M, Estey E H, Appelbaum F R, Walter R B
Department of Laboratory Medicine, Division of Hematopathology, University of Washington, Seattle, WA, USA.
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Leukemia. 2016 Jul;30(7):1456-64. doi: 10.1038/leu.2016.46. Epub 2016 Feb 29.
Measurable ('minimal') residual disease (MRD) before or after hematopoietic cell transplantation (HCT) identifies adults with AML at risk of poor outcomes. Here, we studied whether peri-transplant MRD dynamics can refine risk assessment. We analyzed 279 adults receiving myeloablative allogeneic HCT in first or second remission who survived at least 35 days and underwent 10-color multiparametric flow cytometry (MFC) analyses of marrow aspirates before and 28±7 days after transplantation. MFC-detectable MRD before (n=63) or after (n=16) transplantation identified patients with high relapse risk and poor survival. Forty-nine patients cleared MRD with HCT conditioning, whereas two patients developed new evidence of disease. The 214 MRD(neg)/MRD(neg) patients had excellent outcomes, whereas both MRD(neg)/MRD(pos) patients died within 100 days following transplantation. For patients with pre-HCT MRD, outcomes were poor regardless of post-HCT MRD status, although survival beyond 3 years was only observed among the 58 patients with decreasing but not the seven patients with increasing peri-HCT MRD levels. In multivariable models, pre-HCT but not post-HCT MRD was independently associated with overall survival and risk of relapse. These data indicate that MRD(pos) patients before transplantation have a high relapse risk regardless of whether or not they clear MFC-detectable disease with conditioning and should be considered for pre-emptive therapeutic strategies.
造血细胞移植（HCT）前后可测量的（“最小”）残留疾病（MRD）可识别出急性髓系白血病（AML）成年患者预后不良的风险。在此，我们研究了移植前后MRD动态变化是否能优化风险评估。我们分析了279例在首次或第二次缓解期接受清髓性异基因HCT且存活至少35天的成年患者，并在移植前和移植后28±7天对骨髓穿刺液进行了10色多参数流式细胞术（MFC）分析。移植前（n = 63）或移植后（n = 16）可通过MFC检测到MRD的患者复发风险高且生存率低。49例患者通过HCT预处理清除了MRD，而2例患者出现了新的疾病证据。214例MRD（阴性）/MRD（阴性）患者预后良好，而MRD（阴性）/MRD（阳性）的2例患者均在移植后100天内死亡。对于移植前有MRD的患者，无论移植后MRD状态如何，预后均较差，尽管仅在58例移植前后MRD水平下降的患者中观察到了3年以上的生存情况，而7例移植前后MRD水平上升的患者未观察到。在多变量模型中，移植前而非移植后的MRD与总生存率和复发风险独立相关。这些数据表明，移植前MRD阳性的患者无论是否通过预处理清除了MFC可检测到的疾病，复发风险都很高，应考虑采取抢先治疗策略。
