伴13q14缺失的初诊多发性骨髓瘤患者的临床特征和治疗反应
|
摘要
目的:探讨伴13q14缺失的初诊多发性骨髓瘤(MM)患者的临床特征和治疗反应。方法:选择初诊MM患者251例,利用荧光原位杂交技术检测其13q14异常情况,应用Kaplan-Meier生存曲线和Cox回归分析13q14缺失对预后的影响。结果:251例中,13q14缺失80例(31.9%)。13q14缺失组初诊时血清钙离子、β2MG、M蛋白水平及骨髓浆细胞水平高于未缺失组,血红蛋白、血小板水平低于未缺失组,DSⅢ期患者比例、ISSⅢ期患者比例均高于未缺失组(P<0.05)。2组OS和PFS生存曲线比较结果显示,13q14缺失组预后差于未缺失组(P<0.05)。Cox回归分析结果显示,13q14缺失是PFS和OS的独立危险因素,HR(95%CI)分别为1.7(1.1～2.7)和2.3(1.2～4.5)。治疗1个疗程、4个疗程后,BD方案组M蛋白下降率均高于传统方案组(P均<0.05)。结论:伴13q14缺失的MM患者初诊时肿瘤负荷高,整体预后差;含硼替佐米方案可改善其预后。
Aim:To investigate the clinical features and response to therapies in de novo multiple myeloma(MM) patients with 13q14 deletion[del(13q14) ].Methods:Clinical data of 251 newly diagnosed MM patients were analyzed retrospectively.The fluorescent in situ hybridization was used for detection of del(13q14),and Kaplan-Meier survival curve and Cox regression were used to study the effects of del(13q14) on MM prognosis.Results:Among the 251 patients,del(13q14) was observed in 80(31.9%) cases.The levels of serum calcium,β2 microglobulin,M protein and marrow plasma cells of the del(13q14) group were higher than those of the non-del(13q14) group,while hemoglobin and platelets were lower,and the proportions of patients in DSⅢ stage or ISSⅢ stage were higher(P<0.05) at the initial diagnosis.The results of Kaplan-Meier survival analysis showed that the prognosis of the del(13q14) group was worse than that of the non-del(13q14) group(P<0.05).Cox regression analysis showed that the del(13q14) was an independent risk factor for PFS and OS,HR(95% CI) was 1.7(1.1-2.7) and 2.3(1.2-4.5).After 1 or 4 courses of treatment,the descending rate of M protein in BD regimen group was higher than traditional regimen group(P<0.05).Conclusion:MM patients with del(13q14) have higher tumor burden at the initial diagnosis and have worse prognosis.Bortezomib regimen could improve the prognosis.
Aim:To investigate the clinical features and response to therapies in de novo multiple myeloma(MM) patients with 13q14 deletion[del(13q14) ].Methods:Clinical data of 251 newly diagnosed MM patients were analyzed retrospectively.The fluorescent in situ hybridization was used for detection of del(13q14),and Kaplan-Meier survival curve and Cox regression were used to study the effects of del(13q14) on MM prognosis.Results:Among the 251 patients,del(13q14) was observed in 80(31.9%) cases.The levels of serum calcium,β2 microglobulin,M protein and marrow plasma cells of the del(13q14) group were higher than those of the non-del(13q14) group,while hemoglobin and platelets were lower,and the proportions of patients in DSⅢ stage or ISSⅢ stage were higher(P<0.05) at the initial diagnosis.The results of Kaplan-Meier survival analysis showed that the prognosis of the del(13q14) group was worse than that of the non-del(13q14) group(P<0.05).Cox regression analysis showed that the del(13q14) was an independent risk factor for PFS and OS,HR(95% CI) was 1.7(1.1-2.7) and 2.3(1.2-4.5).After 1 or 4 courses of treatment,the descending rate of M protein in BD regimen group was higher than traditional regimen group(P<0.05).Conclusion:MM patients with del(13q14) have higher tumor burden at the initial diagnosis and have worse prognosis.Bortezomib regimen could improve the prognosis.
引文
[1]SAXE D,SEO EJ,BERGERON MB,et al.Recent advances in cytogenetic characterization of multiple myeloma[J].Int J Lab Hematol,2018.doi:10.1111/ijlh.12882
[2]KAPOOR P,FONSECA R,RAJKUMAR SV,et al.Evidence for cytogenetic and fluorescence in situ hybridization risk stratification of newly diagnosed multiple myeloma in the era of novel therapies[J].Mayo Clin Proc,2010,85(6):532
[3]FACON T,AVET-LOISEAU H,GUILLERM G,et al.Chromosome 13 abnormalities identified by FISH analysis and serum beta2-microglobulin produce a powerful myeloma staging system for patients receiving high-dose therapy[J].Blood,2001,97(6):1566
[4]中国医师协会血液科医师分会,中华医学会血液学分会,中国医师协会多发性骨髓瘤专业委员会.中国多发性骨髓瘤诊治指南:2017年修订[J].中华内科杂志,2017,56(11):866
[5]杨强,侯健,陈文明,等.双克隆免疫球蛋白多发性骨髓瘤六例报告并文献复习[J].中华血液学杂志,2016,37(7):614
[6]ZOJER N,KONIGSBERG R,ACKERMANN J,et al.Deletion of 13q14 remains an independent adverse prognostic variable in multiple myeloma despite its frequent detection by interphase fluorescence in situ hybridization[J].Blood,2000,95(6):1925
[7]OH S,KOO DH,KWON MJ,et al.Chromosome 13 deletion and hypodiploidy on conventional cytogenetics are robust prognostic factors in Korean multiple myeloma patients:web-based multicenter registry study[J].Ann Hematol,2014,93(8):1353
[8]AVET-LOISEAU H,SOULIER J,FERMAND JP,et al.Impact of high-risk cytogenetics and prior therapy on outcomes in patients with advanced relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone[J].Leukemia,2010,24(3):623
[9]JUNG HA,JANG MA,KIM K,et al.Clinical utility of a diagnostic approach to detect genetic abnormalities in multiple myeloma:a single institution experience[J].Ann Lab Med,2018,38(3):196
[10]GRZASKO N,HAJEK R,HUS M,et al.Chromosome 1 amplification has similar prognostic value to del(17p13)and t(4;14)(p16;q32)in multiple myeloma patients:analysis of real-life data from the Polish Myeloma Study Group[J].Leuk Lymphoma,2017,58(9):2089
[11]AVET-LOISEAU H,ATTAL M,CAMPION L,et al.Longterm analysis of the IFM 99 trials for myeloma:cytogenetic abnormalities[t(4;14),del(17p),1q gains]play a major role in defining long-term survival[J].J Clin Oncol,2012,30(16):1949
[12]SHIN SY,EOM HS,SOHN JY,et al.Prognostic implications of monosomies in patients with multiple myeloma[J].Clin Lymphoma Myeloma Leuk,2017,17(3):159
[13]DIMOPOULOS MA,ORLOWSKI RZ,FACON T,et al.Retrospective matched-pairs analysis of bortezomib plus dexamethasone versus bortezomib monotherapy in relapsed multiple myeloma[J].Haematologica,2015,100(1):100
[14]XIAO GW,LI YQ,WANG YY,et al.LncRNA PRAL is closely related to clinical prognosis of multiple myeloma and the bortezomib sensitivity[J].Exp Cell Res,2018,370(2):254
[2]KAPOOR P,FONSECA R,RAJKUMAR SV,et al.Evidence for cytogenetic and fluorescence in situ hybridization risk stratification of newly diagnosed multiple myeloma in the era of novel therapies[J].Mayo Clin Proc,2010,85(6):532
[3]FACON T,AVET-LOISEAU H,GUILLERM G,et al.Chromosome 13 abnormalities identified by FISH analysis and serum beta2-microglobulin produce a powerful myeloma staging system for patients receiving high-dose therapy[J].Blood,2001,97(6):1566
[4]中国医师协会血液科医师分会,中华医学会血液学分会,中国医师协会多发性骨髓瘤专业委员会.中国多发性骨髓瘤诊治指南:2017年修订[J].中华内科杂志,2017,56(11):866
[5]杨强,侯健,陈文明,等.双克隆免疫球蛋白多发性骨髓瘤六例报告并文献复习[J].中华血液学杂志,2016,37(7):614
[6]ZOJER N,KONIGSBERG R,ACKERMANN J,et al.Deletion of 13q14 remains an independent adverse prognostic variable in multiple myeloma despite its frequent detection by interphase fluorescence in situ hybridization[J].Blood,2000,95(6):1925
[7]OH S,KOO DH,KWON MJ,et al.Chromosome 13 deletion and hypodiploidy on conventional cytogenetics are robust prognostic factors in Korean multiple myeloma patients:web-based multicenter registry study[J].Ann Hematol,2014,93(8):1353
[8]AVET-LOISEAU H,SOULIER J,FERMAND JP,et al.Impact of high-risk cytogenetics and prior therapy on outcomes in patients with advanced relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone[J].Leukemia,2010,24(3):623
[9]JUNG HA,JANG MA,KIM K,et al.Clinical utility of a diagnostic approach to detect genetic abnormalities in multiple myeloma:a single institution experience[J].Ann Lab Med,2018,38(3):196
[10]GRZASKO N,HAJEK R,HUS M,et al.Chromosome 1 amplification has similar prognostic value to del(17p13)and t(4;14)(p16;q32)in multiple myeloma patients:analysis of real-life data from the Polish Myeloma Study Group[J].Leuk Lymphoma,2017,58(9):2089
[11]AVET-LOISEAU H,ATTAL M,CAMPION L,et al.Longterm analysis of the IFM 99 trials for myeloma:cytogenetic abnormalities[t(4;14),del(17p),1q gains]play a major role in defining long-term survival[J].J Clin Oncol,2012,30(16):1949
[12]SHIN SY,EOM HS,SOHN JY,et al.Prognostic implications of monosomies in patients with multiple myeloma[J].Clin Lymphoma Myeloma Leuk,2017,17(3):159
[13]DIMOPOULOS MA,ORLOWSKI RZ,FACON T,et al.Retrospective matched-pairs analysis of bortezomib plus dexamethasone versus bortezomib monotherapy in relapsed multiple myeloma[J].Haematologica,2015,100(1):100
[14]XIAO GW,LI YQ,WANG YY,et al.LncRNA PRAL is closely related to clinical prognosis of multiple myeloma and the bortezomib sensitivity[J].Exp Cell Res,2018,370(2):254