Quantitative monitoring of NPM1 mutations provides a valid minimal residual disease parameter following allogeneic stem cell transplantation
Quantitative monitoring of NPM1 mutations provides a valid minimal residual disease parameter following allogeneic stem cell transplantation
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DOI：
10.1016/j.exphem.2008.09.014
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发表时间：
2009-01-01
影响因子：
2.6
通讯作者：
Kroeger, Nicolaus
中科院分区：
文献类型：
--
作者：
Bacher, Ulrike;Badbaran, Anita;Kroeger, Nicolaus
背景异基因造血干细胞移植（SCT）后，急性髓系白血病（AML）微小残留病（MRD）的诊断越来越重要。核磷蛋白（NPM 1）突变，其高频率的AML，建议代表合适的MRD标记，但到目前为止，没有研究已经评估其有用性在posttransplantation period.Materials and Methods。我们在一个队列或13例NPM 1A突变（NPM 1Amut）患者中评估了移植后MRD标记物的有效性。对于这种最常见的NPM 1A亚型，采用实时荧光定量聚合酶链反应（qPCR）方法，对SCT前后骨髓/外周血标本进行回顾性分析。NPM 1Amut在13例接受14次移植的患者中进行了回顾性随访。进行了139次qPCR分析（中位数：7个时间点;中位数随访：216天;范围：35-1825天）。SCT后，14例NPM 1Amut病例中有10例（71%）变为PCR阴性，其中4例获得稳定缓解。所有四名在SCT后NPM 1Amut仍呈阳性的患者（29%）均复发。在所有9例复发病例中，在形态学复发和分子嵌合体减少之前观察到NPM 1Amut的增加，平均间隔分别为24天（范围，12-38天）和15天（范围，1-36天）。NPM 1Amut的定量评估似乎提供了一个可靠的MRD标志物在移植阳性期间，预测复发早于形态学或分子嵌合体，这应该在更大的研究中证实。(C)2009 ISEH -血液学和干细胞学会。爱思唯尔公司出版
Background. Minimal residual disease (MRD) diagnostics in acute myeloid leukemia (AML) gain increasing importance after allogeneic stem cell transplantation (SCT). Nucleophosmin (NPM1) mutations, with their high frequency in AML, were suggested to represent suitable MRD markers, but so far no study has evaluated their usefulness in the posttransplantation period.Materials and Methods. We evaluated the validity of this MRD marker in the posttransplantation period in a cohort or 13 patients with an NPM1A mutation (NPM1Amut). For this most frequent NPM1A subtype., quantitative real-time polymerase chain reaction (qPCR), was retrospectively performed oil bone marrow/peripheral blood samples that had been taken before and after SCT,Results. NPM1Amut was retrospectively followed up in 13 patients who received 14 transplantations. One-hundred and thirty-nine qPCR analyses were performed (median: 7 time points; median follow-up: 216 days; range, 35-1825 days). After SCT, 10 of 14 NPM1Amut cases (71%) became PCR-negative, of which four achieved stable remissions. All four patients (29%) who remained NPM1Amut-positive after SCT relapsed. In all nine relapse cases, increases of NPM1Amut were seen that preceded morphological relapse and the decrease of molecular chimerism with mean intervals of 24 days (range, 12-38 days) and 15 days (range, 1-36 days), respectively.Conclusions. Quantitative assessment of NPM1Amut seems to provide a reliable MRD marker in the positransplantation period, predicting relapse earlier than morphology or molecular chimerism, which should be confirmed in larger studies. (C) 2009 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.