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通过荧光聚合酶链反应评估多发性骨髓瘤患者的微小残留病:实现分子缓解的预后影响。

Evaluation of minimal residual disease in multiple myeloma patients by fluorescent-polymerase chain reaction: the prognostic impact of achieving molecular response.

作者信息

Martínez-Sánchez Pilar, Montejano Laura, Sarasquete Maria Eugenia, García-Sanz Ramón, Fernández-Redondo Elena, Ayala Rosa, Montalbán María Angeles, Martínez Rafael, García Laraña José, Alegre Adrian, Hernández Belen, Lahuerta Juan José, Martínez-López Joaquín

机构信息

Servicio de Hematología, Hospital Universitario 12 de Octubre, Madrid, Spain.

出版信息

Br J Haematol. 2008 Sep;142(5):766-74. doi: 10.1111/j.1365-2141.2008.07263.x. Epub 2008 Jul 8.

Abstract

This study aimed to standardize a simple molecular method for evaluating the response to treatment in multiple myeloma (MM) patients after high dose chemotherapy. Fifty three patients enrolled in the GEM2000 protocol were studied for minimal residual disease (MRD) using both fluorescent-polymerase chain reaction (F-PCR) and flow cytometry. Most patients had achieved complete remission or very good response after autologous stem cell transplantation. The molecular analysis of immunoglobulin gene rearrangements at diagnosis and during the follow-up was carried out by F-PCR according to the Biomed-2 protocols. F-PCR could be used in 91% of the patients and the results were similar to flow cytometry. F-PCR was able to identify a group of patients with a better prognosis [progression-free survival (PFS) 67.86% in patients with negative F-PCR vs. 28%; P = 0.001], even amongst patients who achieved a complete response with negative immunofixation (PFS 75% vs. 25%; P = 0.002). Multivariate analysis identified the F-PCR result as the only variable to show a prognostic value when PFS was analysed. F-PCR of DHJ and light chain rearrangements of immunoglobulin genes is a feasible method for evaluating MRD in MM patients after intensive therapy. Achieving molecular response by F-PCR shows prognostic value.

摘要

本研究旨在规范一种简单的分子方法,用于评估多发性骨髓瘤(MM)患者在大剂量化疗后的治疗反应。对53例参加GEM2000方案的患者,使用荧光聚合酶链反应(F-PCR)和流式细胞术研究微小残留病(MRD)。大多数患者在自体干细胞移植后达到完全缓解或非常好的反应。根据Biomed-2方案,通过F-PCR对诊断时和随访期间的免疫球蛋白基因重排进行分子分析。F-PCR可用于91%的患者,结果与流式细胞术相似。F-PCR能够识别出一组预后较好的患者[F-PCR阴性患者的无进展生存期(PFS)为67.86%,而F-PCR阳性患者为28%;P=0.001],即使在免疫固定阴性且达到完全缓解的患者中也是如此(PFS为75%对25%;P=0.002)。多变量分析确定,在分析PFS时,F-PCR结果是唯一显示预后价值的变量。免疫球蛋白基因的重链-轻链连接(DHJ)和轻链重排的F-PCR是评估MM患者强化治疗后MRD的可行方法。通过F-PCR实现分子反应显示出预后价值。

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