多发性骨髓瘤微小残留病及其检测方法
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摘要
多发性骨髓瘤完全缓解,是指血清和尿免疫固定电泳阴性,不存在任何软组织浆细胞瘤,以及骨髓中浆细胞小于5%,超过一半的患者可以达到完全缓解。达到完全缓解后,部分患者体内仍有微量残留的肿瘤细胞,存在很高复发风险,相比传统完全缓解的评价标准,微小残留病更能客观反映疾病的缓解状态。近年来,流式细胞术、基因测序等方法用于多发性骨髓瘤疗效判定及其微小残留病检测,受到了广泛关注。本文就上述检测方法在多发性骨髓瘤微小残留病患者检测方面的研究进展进行综述。
The complete remission of multiple myeloma refers to the negative serum and urine immunofixation electrophoresis,with no soft tissue plasmacytoma,and less than 5% of the plasma cells in the bone marrow,and more than half of the patients can achieve complete remission.After that,some of the patients still have trace residual MM cells,and there is a high risk of recurrence.Compared with the traditional CR evaluation criteria,minimal residual disease can reflect the remission status of the disease more objectively.In recent years,FCM and gene sequencing have been widely used in the diagnosis of MM and the detection of minimal residual disease(MRD).This article reviews the progress of the above methods in detecting MRD in MM patients.
The complete remission of multiple myeloma refers to the negative serum and urine immunofixation electrophoresis,with no soft tissue plasmacytoma,and less than 5% of the plasma cells in the bone marrow,and more than half of the patients can achieve complete remission.After that,some of the patients still have trace residual MM cells,and there is a high risk of recurrence.Compared with the traditional CR evaluation criteria,minimal residual disease can reflect the remission status of the disease more objectively.In recent years,FCM and gene sequencing have been widely used in the diagnosis of MM and the detection of minimal residual disease(MRD).This article reviews the progress of the above methods in detecting MRD in MM patients.
引文
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[16]Engelhardt M,Terpos E.Klebel-M,et al.European Myeloma Network recommendations on the evaluation and treatment of newly diagnosed patients with multiple myeloma[J].Haematologica,2014,99(2):232-242.
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[18]Flores-Montero J,Sanoja-Flores L,Paiva B,et al.Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma[J].Leukemia,2017,31(10):2094-2103.
[19]李晓帆.王少元多发性骨髓瘤微小残留病检测及其临床应用(福建医科大学附属协和医院血液科[J].福建省血液病研究所,福建省血液病重点实验室,福建福州350001)1671-2870(2017)05-0472-05.
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[21]Huff CA,Matsui W.Multiple myeloma cancer stem cells[J].J Clin Oncol,2008,26(17):2895-900.
[22]Puig N,Sarasquete ME,Balanzategui A,et al.Critical evaluation of ASO RQ-PCR for minimal residual disease evaluation in multiple myeloma.A comparative analysis with flow cytometry[J].Leukemia,2014,28(2):391-397.
[23]González D,González M,Alonso ME,et al.Incomplete DJH rearrangements as a novel tumor target for minimal residual disease quantitation in multiple myeloma using real-time PCR[J].Leukemia,2003,17(6):1051-1057.
[24]Sata H,Shibayama H,Maeda I,et al.Quantitative polymerase chain reaction analysis with allele-specific oligonucleotide primers for individual Ig H VDJ regions to evaluate tumor burden in myeloma patients[J].Exp Hematol,2015,43(5):374-381.
[25]Sedlarikova L,Kubiczkova L,Kryukov F,et al.Detection of tumor-specific marker for minimal residual disease in multiple myeloma patients[J].Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub,2015,159(4):554-561.
[26]艾晓非,王晓静,王波,等.BIOMED-2标准化Ig基因重排在多发性骨髓瘤中的应用研究I-J].中华血液学杂志,2015,36(11):918-921.
[27]Martinez-Lopez J,Lahuerta JJ,Pepin F,et al.Prognostic value of deep sequencing method for minimal residual disease detection in multiple myeloma[J].Blood,2014,123(20):3073-3079.
[28]Boyd SD,Marshall EL,Merker JD,et al.Measurement and clinical monitoring of human lymphocyte clonality by massively parallel VDJ pyrosequencing[J].Sci Transl Med,2009;1(12):12ra23
[29]张冰云,李振宇.多发性骨髓瘤微小残留病检测研究进展[J].国际输血及血液学杂志,2016,39(3).
[30]Flanders A,Stet Ier-Stevenson M,Landgren O.Minimal residual disease testing in multiple myeloma by flow cytometry:major heterogeneity[J].Blood,2013,122(6):1088-1089.
[31]李翰卿,翟勇平.流式细胞术检测多发性骨髓瘤免疫表型和残留病灶的研究进展[J].中国实验血液学杂志,2015,23(1):241-245.
[32]Ladetto M,Br¨uggemann M,Monitillo L,et al.Next-generation sequencing and real-time quantitative PCR for minimal residual disease detection in B-cell disorders[J].Leukemia,2014,28(6):1299-1307.
[2]Faham M,Zheng J,Moorhead M,et al.Deep-sequencing approach for minimal residual disease detection in acutely mphoblastic zeukemia[J].Blood,2012,120(26):5173-5180.
[3]Martinez-Lopez J,Blade J,Mateos MV,et al.Grupo Espan'ol de MM;Programa para el Estudio de la Terap'e utica en Hemopat'ta Maligna.Longterm prognostic significance of response in multiple myeloma after stem cell transplantation[J].Blood,2011,118(3):529-534.
[4]Barlogie B,Mitchell A,van Rhee F,et al.Curing myeloma at last:defining criteria and providing the evidence[J].Blood,2014,124(20):3043-3051.
[5]Faith E,Andrew C,Roger G,et al.Minimal residu aldisease monitoring in Multiple Myeloma[J].Best practice&Research clinical Haematology,2002,15:197-222.
[6]Roland F,Rainer H,Ralf K.Molecular monioring of minimal residual disease in patients with multiple myeloma[J].Hematology,2004,9:17-33.
[7]林如峰,陆化.多发性骨髓瘤完全缓解后微小残留病变的检测进展及意义白血病[J].淋巴瘤,2006,15(1).
[8]Adnan AZ,David H V.M ultiple my eloma:an old disease with new hope for the future[J].Can Cancer J C lin,2001,51(5):273-285.
[9]Rawstron AC,Child JA,de Tute RM,et al.Minimal residual disease assessed by multiparameter flow cytometry in multiple myeloma:impact on outcome in the Medical Research Council Myeloma IXStudy[J].J Clin Oncol,2013,31(20):2540-2547.
[10]俞晴,施菊妹,陶怡.微小残留病灶在多发性骨髓瘤中的临床意义及其检测方法[J].中国实验血液学杂志,2017,25(3):961-964.
[11]Pavia B,van Dongen JJ,orfao A.New criteria for responce assessment:role of minimal residual disease in multiple myeloma[J].Blood,2015,125(20):3059-3068.
[12]李春儿,王晔恺,周吉航,等.方国安多发性骨髓瘤的实验室诊断及流式微小残留病变分析[J].浙江省舟山医院(316004).
[13]侯健,樊建玲.微小残留病检测在多发性骨髓瘤中的意义[J].中华医学杂志,2015,95(10).
[14]ailankody S,Korde N,Lesokhin AM,et al.Minimal residual disease in multiple myeloma:bringing the bench to the bedside[J].Nat Rev Clin Oncol,2015,12(5):286-295.
[15]Landgren O,Gorm Ley N,Turley D,et al.Flow cytometry detection of minimal residual disease in multiple myeloma:lessons learned at FDA-NCI roundable symposium[J].Am J Hematol,2014,89(12):1159-1160.
[16]Engelhardt M,Terpos E.Klebel-M,et al.European Myeloma Network recommendations on the evaluation and treatment of newly diagnosed patients with multiple myeloma[J].Haematologica,2014,99(2):232-242.
[17]Weng XQ,Shen Y,Sheng Y,et al.Prognostic significance of monitoring leukemia-associated immunophenotypes by eight-color flow cytometry in adult B-acute lymphoblastic leukemia[J].Blood Cancer J.2013,3:e133.
[18]Flores-Montero J,Sanoja-Flores L,Paiva B,et al.Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma[J].Leukemia,2017,31(10):2094-2103.
[19]李晓帆.王少元多发性骨髓瘤微小残留病检测及其临床应用(福建医科大学附属协和医院血液科[J].福建省血液病研究所,福建省血液病重点实验室,福建福州350001)1671-2870(2017)05-0472-05.
[20]李护君,李振宇,徐开林.多发性骨髓瘤的分层及微小残留病检测[J].国际输血及血液学杂志,2016,39(3).
[21]Huff CA,Matsui W.Multiple myeloma cancer stem cells[J].J Clin Oncol,2008,26(17):2895-900.
[22]Puig N,Sarasquete ME,Balanzategui A,et al.Critical evaluation of ASO RQ-PCR for minimal residual disease evaluation in multiple myeloma.A comparative analysis with flow cytometry[J].Leukemia,2014,28(2):391-397.
[23]González D,González M,Alonso ME,et al.Incomplete DJH rearrangements as a novel tumor target for minimal residual disease quantitation in multiple myeloma using real-time PCR[J].Leukemia,2003,17(6):1051-1057.
[24]Sata H,Shibayama H,Maeda I,et al.Quantitative polymerase chain reaction analysis with allele-specific oligonucleotide primers for individual Ig H VDJ regions to evaluate tumor burden in myeloma patients[J].Exp Hematol,2015,43(5):374-381.
[25]Sedlarikova L,Kubiczkova L,Kryukov F,et al.Detection of tumor-specific marker for minimal residual disease in multiple myeloma patients[J].Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub,2015,159(4):554-561.
[26]艾晓非,王晓静,王波,等.BIOMED-2标准化Ig基因重排在多发性骨髓瘤中的应用研究I-J].中华血液学杂志,2015,36(11):918-921.
[27]Martinez-Lopez J,Lahuerta JJ,Pepin F,et al.Prognostic value of deep sequencing method for minimal residual disease detection in multiple myeloma[J].Blood,2014,123(20):3073-3079.
[28]Boyd SD,Marshall EL,Merker JD,et al.Measurement and clinical monitoring of human lymphocyte clonality by massively parallel VDJ pyrosequencing[J].Sci Transl Med,2009;1(12):12ra23
[29]张冰云,李振宇.多发性骨髓瘤微小残留病检测研究进展[J].国际输血及血液学杂志,2016,39(3).
[30]Flanders A,Stet Ier-Stevenson M,Landgren O.Minimal residual disease testing in multiple myeloma by flow cytometry:major heterogeneity[J].Blood,2013,122(6):1088-1089.
[31]李翰卿,翟勇平.流式细胞术检测多发性骨髓瘤免疫表型和残留病灶的研究进展[J].中国实验血液学杂志,2015,23(1):241-245.
[32]Ladetto M,Br¨uggemann M,Monitillo L,et al.Next-generation sequencing and real-time quantitative PCR for minimal residual disease detection in B-cell disorders[J].Leukemia,2014,28(6):1299-1307.