Peter Bader, Hermann Kreyenberg, Emilia Salzmann-Manrique, Andre M. Willasch, and Thomas E. Klingebiel, University Hospital for Children and Adolescents, Frankfurt/Main; Arend von Stackelberg and Cornelia Eckert, Children's Hospital Charité, Berlin, Berlin; Roland Meisel, Heinrich-Heine-University, Düsseldorf; Daniel Stachel, University Hospital Erlangen, Erlangen; Martin Schrappe, Julia Alten, Andre Schrauder, Christian-Albrechts-University and Medical Center Schleswig-Holstein, Kiel; Ansgar Schulz, University Medical Center, Ulm; Peter Lang, University Children's Hospital, Tuebingen; Ingo Müller, University Medical Center Hamburg-Eppendorf, Hamburg; Michael H. Albert, University Children's Hospital, Munich, Germany; and Ulrike Poetschger and Christina Peters, St Anna Children's Hospital, Vienna, Austria.
J Clin Oncol. 2015 Apr 10;33(11):1275-84. doi: 10.1200/JCO.2014.58.4631. Epub 2015 Jan 20.
To elucidate the impact of minimal residual disease (MRD) after allogeneic transplantation, the Acute Lymphoblastic Leukemia Berlin-Frankfurt-Münster Stem Cell Transplantation Group (ALL-BFM-SCT) conducted a prospective clinical trial.
In the ALL-BFM-SCT 2003 trial, MRD was assessed in the bone marrow at days +30, +60, +90, +180, and +365 after transplantation in 113 patients with relapsed disease. Standardized quantification of MRD was performed according to the guidelines of the Euro-MRD Group.
All patients showed a 3-year probability of event-free survival (pEFS) of 55%. The cumulative incidence rates of relapse and treatment-related mortality were 32% and 12%, respectively. The pEFS was 60% for patients who received their transplantations in second complete remission, 50% for patients in ≥ third complete remission, and 0% for patients not in remission (P = .015). At all time points, the level of MRD was inversely correlated with event-free survival (EFS; P < .004) and positively correlated with the cumulative incidence of relapse (P < .01). A multivariable Cox model was fitted for each time point, which showed that MRD ≥ 10(-4) leukemic cells was consistently correlated with inferior EFS (P < .003). The accuracy of MRD measurements in predicting relapse was investigated with time-dependent receiver operating curves at days +30, +60, +90, and +180. From day +60 onward, the discriminatory power of MRD detection to predict the probability of relapse after 1, 3, 6, and 9 months was more than 96%, more than 87%, more than 71%, and more than 61%, respectively.
MRD after transplantation was a reliable marker for predicting impending relapses and could thus serve as the basis for pre-emptive therapy.
为了阐明异基因移植后微小残留病（MRD）的影响，急性淋巴细胞白血病柏林-法兰克福-慕尼黑干细胞移植组（ALL-BFM-SCT）进行了一项前瞻性临床试验。
在 ALL-BFM-SCT 2003 试验中，在 113 例复发疾病患者中，在移植后第 30、60、90、180 和 365 天，对骨髓中的 MRD 进行了评估。根据 Euro-MRD 组的指南，对 MRD 进行了标准化定量。
所有患者的 3 年无事件生存（pEFS）概率为 55%。复发和治疗相关死亡率的累积发生率分别为 32%和 12%。在第二次完全缓解时接受移植的患者的 pEFS 为 60%，在≥第三次完全缓解的患者为 50%，未缓解的患者为 0%（P =.015）。在所有时间点，MRD 水平与无事件生存（EFS）呈负相关（P <.004），与复发的累积发生率呈正相关（P <.01）。为每个时间点拟合了多变量 Cox 模型，结果表明，MRD≥10（-4）个白血病细胞与较差的 EFS 始终相关（P <.003）。通过时间依赖性接收器工作曲线，在第 30、60、90 和 180 天，对 MRD 测量预测复发的准确性进行了研究。从第 60 天开始，MRD 检测预测 1、3、6 和 9 个月后复发概率的区分能力分别超过 96%、87%、71%和 61%。
移植后 MRD 是预测即将发生的复发的可靠标志物，因此可以作为抢先治疗的基础。
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