Corradini P, Voena C, Tarella C, Astolfi M, Ladetto M, Palumbo A, Van Lint M T, Bacigalupo A, Santoro A, Musso M, Majolino I, Boccadoro M, Pileri A
Dipartimento di Medicina ed Oncologia Sperimentale, Azienda Ospedaliera San Giovanni Battista-Divisione Universitaria di Ematologia, Torino, Italy.
J Clin Oncol. 1999 Jan;17(1):208-15. doi: 10.1200/JCO.1999.17.1.208.
To describe molecular monitoring of minimal residual disease in patients with myeloma who have achieved complete remission (CR) after autologous or allogeneic transplantation of hematopoietic cells.
Clonal markers based upon the rearrangement of immunoglobulin heavy-chain genes were generated for each patient and used for polymerase chain reaction (PCR) detection of residual myeloma cells. Fifty-one patients entered the program and 36 achieved CR. After transplantation, molecular monitoring was performed on 29 patients (15 autologous and 14 allogeneic transplants) who had molecular markers.
Our data show that molecular remissions are rarely achieved (7%) with high-dose chemotherapy followed by single or double autografting. In addition, virtually all peripheral blood progenitor cell and bone marrow samples contained residual myeloma cells, even when sample collection was scheduled after repeated courses of high-dose chemotherapy. All patients autografted with PCR-positive cells remain positive, and eight of 15 have relapsed. Two patients were autografted with PCR-negative cells: one is in clinical and molecular remission, and one relapsed 25 months after the transplant. In the allografting setting, a higher proportion of patients (50%) achieved molecular remission; there were two relapses, one in the PCR-positive group and one in the PCR-negative group.
This is the first large study of molecular remissions in myeloma patients to use a PCR-based approach utilizing patient-specific tumor markers. The sizeable fraction of patients who achieved molecular remission after allografting with peripheral blood progenitor cells represents a promising finding in an incurable disease.
描述接受造血细胞自体或异基因移植后达到完全缓解（CR）的骨髓瘤患者微小残留病的分子监测情况。
为每位患者生成基于免疫球蛋白重链基因重排的克隆标志物，并用于聚合酶链反应（PCR）检测残留的骨髓瘤细胞。51例患者进入该项目，36例达到CR。移植后，对29例具有分子标志物的患者（15例自体移植和14例异基因移植）进行了分子监测。
我们的数据显示，高剂量化疗后进行单次或双次自体移植很少能实现分子缓解（7%）。此外，几乎所有外周血祖细胞和骨髓样本都含有残留的骨髓瘤细胞，即使样本采集安排在重复高剂量化疗疗程之后。所有移植PCR阳性细胞的患者仍为阳性，15例中有8例复发。2例患者移植了PCR阴性细胞：1例处于临床和分子缓解状态，1例在移植后25个月复发。在异基因移植组，较高比例的患者（50%）实现了分子缓解；有2例复发，1例在PCR阳性组，1例在PCR阴性组。
这是第一项使用基于PCR的方法、利用患者特异性肿瘤标志物对骨髓瘤患者分子缓解情况进行的大型研究。在外周血祖细胞异基因移植后实现分子缓解的患者比例相当可观，这在一种无法治愈的疾病中是一个有希望的发现。
