Clinical applicability and prognostic significance of molecular response assessed by fluorescent-PCR of immunoglobulin genes in multiple myeloma. Results from a GEM/PETHEMA study

Clinical applicability and prognostic significance of molecular response assessed by fluorescent-PCR of immunoglobulin genes in multiple myeloma. Results from a GEM/PETHEMA study
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DOI:
10.1111/bjh.12576
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发表时间:
2013-12-01
影响因子:
6.5
通讯作者:
Lahuerta, Juan Jose
Lahuerta, Juan Jose
中科院分区:
医学2区
文献类型:
--
作者:
Martinez-Lopez, Joaquin;Fernandez-Redondo, Elena;Lahuerta, Juan Jose

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微小残留病监测在多发性骨髓瘤(MM)中变得越来越重要,但多参数流式细胞术(MFC)和等位基因特异性寡核苷酸聚合酶链反应(ASO-PCR)技术并不常用。本研究在来自Grupo Espanol Multidisciplinar de Melanoma(GEM)2000/GEM 05试验(NCT 00560053、NCT 00443235、NCT 00464217)的130例新诊断的MM患者中研究了通过荧光PCR(F-PCR)评估实现分子缓解对预后的影响,这些患者在诱导治疗后几乎实现了非常好的部分缓解。作为参考,我们使用了同步MFC观察到的结果。使用三种不同的多重PCR:IGH D-J、IGK V-J和KDE重排对DNA进行诊断时的F-PCR。F-PCR的适用性为91.5%。诱导治疗后,64例患者达到分子学缓解,66例非分子学缓解;中位无进展生存期(PFS)分别为61个月和36个月(P= 0.001)。分子学缓解组患者未达到中位总生存期(NR)(5年生存率:75%),而非分子学缓解组为66个月(P= 0.03)。免疫表型应答患者与非免疫表型应答患者的相应PFS和OS值分别为67个月与42个月(P= 0.005)和NR(5年生存率:95%)与69个月(P= 0.004)。F-PCR分析是一种快速、经济、易于实施的技术,在某些情况下,可能是MM微小残留病研究的有效方法。
Minimal residual disease monitoring is becoming increasingly important in multiple myeloma (MM), but multiparameter flow cytometry (MFC) and allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) techniques are not routinely available. This study investigated the prognostic influence of achieving molecular response assessed by fluorescent-PCR (F-PCR) in 130 newly diagnosed MM patients from Grupo Espanol Multidisciplinar de Melanoma (GEM)2000/GEM05 trials (NCT00560053, NCT00443235, NCT00464217) who achieved almost very good partial response after induction therapy. As a reference, we used the results observed with simultaneous MFC. F-PCR at diagnosis was performed on DNA using three different multiplex PCRs: IGH D-J, IGK V-J and KDE rearrangements. The applicability of F-PCR was 915%. After induction therapy, 64 patients achieved molecular response and 66 non-molecular response; median progression-free survival (PFS) was 61 versus 36months, respectively (P=0001). Median overall survival (OS) was not reached (NR) in molecular response patients (5-year survival: 75%) versus 66months in the non-molecular response group (P=003). The corresponding PFS and OS values for patients with immunophenotypic versus non-immunophenotypic response were 67 versus 42months (P=0005) and NR (5-year survival: 95%) versus 69months (P=0004), respectively. F-PCR analysis is a rapid, affordable, and easily performable technique that, in some circumstances, may be a valid approach for minimal residual disease investigations in MM.