Martinelli G, Terragna C, Zamagni E, Ronconi S, Tosi P, Lemoli R M, Bandini G, Motta M R, Testoni N, Amabile M, Ottaviani E, Vianelli N, de Vivo A, Gozzetti A, Tura S, Cavo M
Institute of Hematology and Medical Oncology "Seràgnoli," University of Bologna, Italy.
J Clin Oncol. 2000 Jun;18(11):2273-81. doi: 10.1200/JCO.2000.18.11.2273.
To assess the clinical relevance of minimal residual disease (MRD) in patients with multiple myeloma (MM), 50 patients were monitored while they were in complete clinical remission (CCR) after autologous or allogeneic stem-cell transplantation.
Stringent molecular monitoring using clonal markers based on rearranged immunoglobulin heavy-chain genes was performed in 44 of 50 MM patients in CCR. Molecular clinical remission (MCR) was defined as more than one consecutive negative polymerase chain reaction (PCR) test result.
Twelve (27%) of 44 molecularly monitored patients achieved MCR; four of the 12 became PCR-positive, and one of these four relapsed. In comparison with patients who did not achieve MCR, patients who achieved MCR had a significantly lower relapse rate (41% v 16%; P <.05) and longer relapse-free survival (35 v 110 months; P <.005). Fourteen of 26 patients in CCR who had received allografts were evaluated on a molecular basis: seven (50%) of the 14 achieved MCR and did not relapse; one of the seven remaining patients relapsed. Thirty of 47 patients in CCR who received autografts were evaluated on a molecular basis: five (16%) of the 30 achieved MCR; two of these five became PCR-negative, and one of these two relapsed. Ten of the 25 remaining patients later relapsed. For these nonrandomized groups, the higher MCR rate after allograft procedures was statistically significant (P <.01; Fisher's exact test).
MCR can be obtained in a relatively high proportion of MM patients who have achieved CCR after undergoing allograft procedures and in a smaller fraction of patients after undergoing autograft procedures. In approximately one fourth of MM patients who achieve CCR after transplantation, it may be possible to keep the disease burden constantly below the PCR threshold. Because MCR was associated with prolonged relapse-free survival, these patients could have a relatively favorable clinical outcome.
为评估微小残留病（MRD）在多发性骨髓瘤（MM）患者中的临床相关性，对50例在自体或异基因干细胞移植后处于完全临床缓解（CCR）的患者进行了监测。
对50例处于CCR的MM患者中的44例，采用基于重排免疫球蛋白重链基因的克隆标志物进行严格的分子监测。分子临床缓解（MCR）定义为连续多次聚合酶链反应（PCR）检测结果为阴性。
44例接受分子监测的患者中有12例（27%）达到MCR；12例中的4例PCR转为阳性，这4例中有1例复发。与未达到MCR的患者相比，达到MCR的患者复发率显著更低（41%对16%；P<.05），无复发生存期更长（35对110个月；P<.005）。26例接受同种异体移植且处于CCR的患者中有14例进行了分子评估：14例中的7例（50%）达到MCR且未复发；其余7例患者中有1例复发。47例接受自体移植且处于CCR的患者中有30例进行了分子评估：30例中的5例（16%）达到MCR；这5例中的2例PCR转为阴性，这2例中有1例复发。其余25例患者中有10例后来复发。对于这些非随机分组，同种异体移植术后较高的MCR率具有统计学意义（P<.01；Fisher精确检验）。
在接受同种异体移植术后达到CCR的MM患者中，相当一部分可获得MCR，而在接受自体移植术后只有一小部分患者可获得。在移植后达到CCR的MM患者中，约四分之一可能将疾病负担持续维持在PCR阈值以下。由于MCR与延长的无复发生存期相关，这些患者可能具有相对良好的临床结局。
