Dept. of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
Integrated Research and Treatment Center for Transplantation (IFB-Tx), Hannover, Germany.
Bone Marrow Transplant. 2018 Nov;53(11):1457-1465. doi: 10.1038/s41409-018-0176-7. Epub 2018 May 2.
Conventional analysis of host chimerism (HC) frequently fails to detect relapse before its clinical manifestation in patients with hematological malignancies after allogeneic stem cell transplantation (allo-SCT). Quantitative PCR (qPCR)-based highly-sensitive chimerism analysis extends the detection limit of conventional (short tandem repeats-based) chimerism analysis from 1 to 0.01% host cells in whole blood. To date, the diagnostic value of highly-sensitive chimerism analysis is hardly defined. Here, we applied qPCR-based chimerism analysis to 901 blood samples of 71 out-patients with hematological malignancies after allo-SCT. Receiver operating characteristics (ROC) curves were calculated for absolute HC values and for the increments of HC before relapse. Using the best cut-offs, relapse was detected with sensitivities of 74 or 85% and specificities of 69 or 75%, respectively. Positive predictive values (PPVs) were only 12 or 18%, but the respective negative predictive values were 98 or 99%. Relapse was detected median 38 or 45 days prior to clinical diagnosis, respectively. Considering also durations of steadily increasing HC of more than 28 days improved PPVs to more than 28 or 59%, respectively. Overall, highly-sensitive chimerism analysis excludes relapses with high certainty and predicts relapses with high sensitivity and specificity more than a month prior to clinical diagnosis.
常规的供者嵌合体（HC）分析常常无法在异基因造血干细胞移植（allo-SCT）后血液恶性肿瘤患者出现临床症状之前检测到复发。基于实时定量 PCR（qPCR）的高灵敏度嵌合体分析将常规（短串联重复序列为基础）嵌合体分析的检测限从全血中的 1%宿主细胞扩展到 0.01%。迄今为止，高灵敏度嵌合体分析的诊断价值很难确定。在这里，我们对 71 例 allo-SCT 后血液恶性肿瘤门诊患者的 901 份血样进行了 qPCR 嵌合体分析。计算了绝对 HC 值和复发前 HC 值增量的受试者工作特征（ROC）曲线。使用最佳截断值，复发的敏感性分别为 74%或 85%，特异性分别为 69%或 75%。阳性预测值（PPV）仅为 12%或 18%，但各自的阴性预测值分别为 98%或 99%。复发分别在临床诊断前 38 天或 45 天被检测到。同时考虑到 HC 持续增加超过 28 天的时间，PPV 分别提高到 28%或 59%以上。总的来说，高灵敏度嵌合体分析可以非常确定地排除复发，并且在临床诊断前一个月以上以高敏感性和特异性预测复发。
