Department for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Germany.
Biol Blood Marrow Transplant. 2010 Oct;16(10):1325-46. doi: 10.1016/j.bbmt.2010.07.001. Epub 2010 Jul 15.
Relapse has become the major cause of treatment failure after allogeneic hematopoietic stem cell transplantation. Outcome of patients with clinical relapse after transplantation generally remains poor, but intervention prior to florid relapse improves outcome for certain hematologic malignancies. To detect early relapse or minimal residual disease, sensitive methods such as molecular genetics, tumor-specific molecular primers, fluorescence in situ hybridization (FISH), and multiparameter flow cytometry (MFC) are commonly used after allogeneic stem cell transplantation to monitor patients, but not all of them are included in the commonly employed disease-specific response criteria. The highest sensitivity and specificity can be achieved by molecular monitoring of tumor- or patient-specific markers measured by polymerase chain reaction-based techniques, but not all diseases have such targets for monitoring. Similar high sensitivity can be achieved by determination of recipient-donor chimerism, but its specificity regarding detection of relapse is low and differs substantially among diseases. Here, we summarize the current knowledge about the utilization of such sensitive monitoring techniques in chronic leukemias, myeloproliferative neoplasms, and lymphoid malignancies based on tumor-specific markers and cell chimerism and how these methods might augment the standard definitions of posttransplant remission, persistence, progression, relapse, and the prediction of relapse. Critically important is the need for standardization of the different residual disease techniques and to assess the clinical relevance of minimal residual disease and chimerism surveillance in individual diseases, which in turn must be followed by studies to assess the potential impact of specific interventional strategies.
移植后复发已成为异基因造血干细胞移植治疗失败的主要原因。移植后临床复发患者的预后通常较差，但在明显复发前进行干预可改善某些血液系统恶性肿瘤的预后。为了检测早期复发或微小残留病，在异基因干细胞移植后，通常会使用分子遗传学、肿瘤特异性分子引物、荧光原位杂交（FISH）和多参数流式细胞术（MFC）等敏感方法来监测患者，但并非所有这些方法都包含在常见的疾病特异性反应标准中。通过聚合酶链反应（PCR）技术测量肿瘤或患者特异性标志物的分子监测可以达到最高的敏感性和特异性，但并非所有疾病都有此类监测目标。通过确定受者-供者嵌合体也可以达到类似的高灵敏度，但它在检测复发方面的特异性较低，并且在不同疾病之间差异很大。在此，我们根据肿瘤特异性标志物和细胞嵌合体，总结了目前关于这些敏感监测技术在慢性白血病、骨髓增生性肿瘤和淋巴恶性肿瘤中的应用的知识，以及这些方法如何增强移植后缓解、持续、进展、复发和复发预测的标准定义。至关重要的是需要标准化不同的残留疾病技术，并评估微小残留病和嵌合体监测在个体疾病中的临床相关性，这反过来又必须通过研究来评估特定干预策略的潜在影响。
