Significance of oligoclonal bands after stem cell transplantation in multiple myeloma cases

Objective: To determine the characteristics of oligoclonal bands that are frequently detected by serum proteinelectrophoresis (SPEP) and immunofixation electrophoresis (IFE) after stem cell transplantation. Methods: Weretrospectively analyzed 56 patients with multiple myeloma (MM) undergoing transplantation, and standardimmunofixation electrophoresis was used to identify and quantify paraproteins. Results: The median follow-upwas 35 months (range, 10-76months) and 21 patients relapsed. Twelve (25.0%) demonstrated oligoclonal bandsafter a median time 1.4 months (range, 1-3months), with a median duration of 5.8 months (range, 1-15months).The majority patients with oligoclonal bands had normal quantities of immunoglobulins and the one year eventfree survival (EFS) was 92%, even higher than for patients without OBs (P=0.002). Conclusion: Oligoclonalbands frequent develop post-transplantation in MM cases. In the vast majority of patients, they may notrepresent relapsed disease, and more likely represent a transient phenomenon representing recovery of impairedimmunoglobulin production.     

多发性骨髓瘤诊断与治疗:现状与挑战

过去的十年中,国内外多发性骨髓瘤(MM)的发病机制、危险分层以及治疗等方面的研究取得了突破性进展.新药的不断出现、嵌合抗原受体重定向T细胞的问世以及异基因造血干细胞移植的开展,使MM患者预后得到了极大改善.     

异基因造血干细胞移植治疗多发性骨髓瘤研究进展

异基因造血干细胞移植（allo-HSCT）是唯一可能治愈多发性骨髓瘤（MM）的方法,但较高的移植相关死亡（TRM）率限制了其应用。尽管减低强度预处理（RIC）的allo-HSCT降低了TRM率,但其疗效仍不优于自体造血干细胞移植（auto—HSCT）。因此需要进一步研究降低移植毒性和促进移植物抗骨髓瘤（GVM）效应的新策略,以便使RIC allo-HSCT更加安全有效。文章对目前allo—HSCT在MM中的研究进展进行了综述。     

适合移植的多发性骨髓瘤患者治疗研究进展

适合移植的多发性骨髓瘤（MM）患者的治疗通常采用三药方案诱导治疗后行造血干细胞采集.对于适合移植患者的标准预处理方案是大剂量美法仑方案.移植后行巩固治疗可提高缓解率.为了获得长期的疾病控制和改善总生存期,用硼替佐米或来那度胺（极高危患者二者联合）进行维持治疗是较合理的选择.随着新药在MM治疗中的应用,患者预后将会得到改善并获得长期的疾病控制.     

Abnormal protein bands in patients with multiple myeloma after haematopoietic stem cell transplantation: does it have a prognostic significance?

Abnormal protein bands (APB) unrelated to the original monoclonal protein occasionally appear in serum immunofixation samples from patients with multiple myeloma (MM) following haematopoietic stem cell transplantation (HCT). To investigate the significance of APB, medical records and serum immunofixation patterns of 53 MM patients, who had undergone HCT (49 autologous and 4 allogeneic) at the stem cell transplantation unit of Gazi University Faculty of Medicine, were reviewed. Patients were staged according to Durie–Salmon and International staging systems (ISS) and disease response was determined according to European Bone Marrow Transplantation (EBMT) criteria. Fourteen (26.4%) of the 53 patients developed APBs after HCT. The median time for the appearance and duration of APB was 3 (range 1–24) and 5.5 (range 1.5–14) months, respectively. Probability of overall survival (OS) at the end of the follow‐up was 77 and 61.4% in patients with and without APB, respectively (p = 0.334). The median duration of follow‐up (767 days (range, 220–2905) vs. 726 days (range, 120–1780) p = 0.545) was not different in patients with and without APB. Probability of progression free survival (PFS) at the end of follow‐up was 28.8% in patients with and 27.7% in patients without APB (p = 0.835). PFS (910 days (range 180–2905) vs. 730 days (range 90–1765) p = 0.835) was longer in patients with APB, though without statistical significance. Thus, the occurrence of APB post‐transplantation is not associated with any adverse long‐term consequences and does not require treatment modification. Copyright © 2010 John Wiley & Sons, Ltd.     

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

 已经证实传统意义上完全缓解（CR）的患者体内仍残留约1010 个肿瘤细胞,是疾病进展和复发的根源。为进一步了解体内残存的肿瘤细胞,聚合酶链反应（polymerase chain reaction,PCR）检测IgH基因单克隆重排、流式细胞术（flow cytometic,FCM）检查细胞表面抗原及染色体异常倍体和荧光原位杂交（flurescence in situ hybridizztion,FISH）分析染色体异常核型可用于临床以监测微小残留病的动态变化,判断预后并指导治疗。     

新药时代造血干细胞移植在多发性骨髓瘤治疗中的地位

 与传统化疗相比,自体造血干细胞移植可提高多发性骨髓瘤（MM）患者的缓解率,延长无进展生存期,是治疗MM的一线方案。但近年来,基于新型药物的联合诱导、巩固和维持治疗提高了MM的治疗效果,对自体造血干细胞移植的地位构成了挑战。异基因造血干细胞移植虽然具有治愈MM的潜能,但移植相关死亡率高,患者的总体生存并未获益。而减低剂量预处理异基因移植虽降低了移植相关死亡率,具有一定的移植物抗骨髓瘤作用,但移植物抗宿主病的发生率高。文章总结了MM干细胞移植相关的临床试验结果,旨在定义新药时代造血干细胞移植在MM治疗中的地位。     

新诊断老年多发性骨髓瘤的预后分层及治疗进展

多发性骨髓瘤是一种好发于中老年人的浆细胞恶性增殖性疾病,目前仍不可治愈,中位诊断年龄为69岁,50％以上的患者在诊断时年龄大于75岁.近年来新药的应用显著改善了多发性骨髓瘤患者的总生存期和无进展生存期,但标准方案并不能让老年多发性骨髓瘤患者受益,可能还会降低患者生活质量,增加死亡率.因此,精准的预后评估及危险度分层对于...     

新药诱导后自体造血干细胞移植对以荧光原位杂交分层的多发性骨髓瘤患者的价值

 　目的　评价新药诱导后自体造血干细胞移植（ASCT）对荧光原位杂交（FISH）标危及高危多发性骨髓瘤患者生存的影响。方法　回顾性分析74例多发性骨髓瘤患者,均接受以硼替佐米和（或）沙利度胺为主的诱导化疗,按FISH检测结果及诱导后是否接受ASCT分为标危移植组、标危化疗组、高危移植组及高危化疗组4组,通过生存分析分别评价ASCT对标危及高危患者生存的影响。结果　74例患者经新药诱导后总缓解率为91.9 %（68／74）,接近完全缓解（nCR）+ 完全缓解（CR）率为62.2 %（46／74）。FISH标危的患者与高危的患者诱导后缓解率分别为93.2 %（41／44）与86.7 %（26／30）（P＝0.592）,nCR+CR率分别为56.8 %（25／44）与70.0 %（21／30）（P＝0.251）。FISH标危的患者中,接受移植的患者与接受化疗巩固的患者无进展生存（PFS）及总生存（OS）差异均无统计学意义（P值分别为0.642和0.652）,而FISH高危的患者中,接受移植的患者比接受化疗巩固的患者PFS延长19.7个月（P＝0.028）,OS延长12.5个月（P＝0.542）。结论　在以硼替佐米和（或）沙利度胺为主的方案诱导后,ASCT对 FISH标危多发性骨髓瘤患者的PFS和OS均没有影响,但可使FISH高危患者的PFS延长。     

Survival of elderly patients with multiple myeloma—Effect of upfront autologous stem cell transplantation

BackgroundThe aim of this study was to determine the value of upfront autologous transplantation (ASCT) in elderly patients (60–79 years) with myeloma.MethodsWe analysed relative survival (RS) of patients diagnosed in 1998–2011 and treated with ASCT within 12 months after diagnosis in Germany (n = 3591; German Registry of Stem Cell Transplantation) and compare RS with survival of myeloma patients diagnosed in the same years in Germany (n = 13,903; population-based German Cancer Registries).ResultsUtilisation of ASCT has increased rapidly between 2000–2002 and 2009–2011 (60–64years: 7.0–43.0%; 65–69 years: 6.6–23.7%; 70–79 years: 0.4–4.0%). Comparison of 5-year RS of patients from the general German myeloma population who have survived the first year after diagnosis with 5-year RS of patients treated with ASCT revealed higher survival for transplanted patients among all age groups (60–64: 59.2% versus 66.1%; 65–69: 57.4% versus 61.7%; 70–79: 51.0% versus 56.6%). RS increased strongly between 2003–2005 and 2009–2011 for the general German myeloma population (+8.5%) and for patients treated with ASCT (+11.8%). Differences in RS between these groups increased over time from +1.9% higher age-standardised survival in transplanted patients in 2003–2005 to 5.2% higher survival in 2009–2011.ConclusionWe conclude that upfront ASCT might be a major contributor to improved survival for elderly myeloma patients in Germany.     

自体干细胞移植治疗伴有严重肾功能不全的多发性骨髓瘤

 肾衰竭是多发性骨髓瘤（MM）患者常见的临床表现。伴有肾衰竭的MM患者对传统化疗的总缓解率为35 %～50 %（完全缓解少见）,中位生存期为4个月～1年,均显著低于肾功能正常患者。有许多中心应用大剂量美法仑以及自体干细胞移植（ASCT）治疗伴有严重肾衰竭的MM患者。目前研究发现,患者肾功能严重程度以及是否接受透析对干细胞动员以及干细胞植入无明显影响。大剂量美法仑以及ASCT后,伴有肾衰竭MM患者的完全缓解率、无事件生存率以及总生存率,分别增加到30 %、20个月以及40个月左右。相当一部分患者脱离透析。但是,该领域存在的问题仍然相当多,如APBSCT导致较高的移植相关死亡率。另外,在沙利度胺、硼替佐米以及雷利度胺等新药应用于临床之后,对于ASCT治疗伴有肾衰竭MM患者的影响如何,也需要进一步探讨。     

自体造血干细胞移植治疗多发性骨髓瘤动员方案的研究进展

骨髓瘤患者动员造血干细胞失败的因素包括高龄、疾病状态、以前使用过美法仑、化疗次数、经历过放疗、采集前外周血CD34+细胞数低。常用的动员方案包括粒细胞集落刺激因子（G-CSF）、化疗联合G-CSF,一些研究显示后者动员效果可能好于前者,但毒副作用也增加。应依据患者的疾病状态和身体状况选择合适的动员方案。普乐沙福是一种新型动员剂,可用于动员失败的高危患者,能获得良好的动员效果。目前,一些含新动员剂的方案正在临床试验中。     

Allogeneic bone marrow transplantation in 24 patients with multiple myeloma reported to the EBMT registry

Twenty-four patients with multiple myeloma received an allogeneic bone-marrow graft from HLA-compatible sibling donors (n = 23), or a twin donor (n = 1). Eighteen patients are alive, 1-36 months post bone-marrow transplantation (median 14 months). Ten of these patients had no signs of multiple myeloma as judged by immunoglobulins in serum, light chains in urine, or the percentage of plasma-cells in bone-marrow aspirate. Bone lesions on X-ray were mainly unchanged. Six patients died from transplant-related complications 3 weeks to 5 months post transplantation. One of these patients had severe acute graft-versus-host disease (aGVHD). In other patients aGVHD was a minor problem. Allogeneic bone-marrow transplantation appears to be a promising method for treatment of a selected group of patients with multiple myeloma.     

自体造血干细胞移植治疗多发性骨髓瘤预处理方案的研究进展

大剂量美法仑(Mel)是多发性骨髓瘤(MM)疗效最肯定的预处理方案.全身放疗(TBI)联合Mel的疗效不优于单用Mel,但不良反应增加.在年轻患者中Mel 200 mg/m2疗效优于Mel 100~140 mg/m2.MelBU、TBC、BCV、MET、MTC、MelBCNU、VMel、MTC以及含有苯达莫司汀的预处理方案可获得同大剂量Mel类似的治疗效果.新预处理方案的效果需要更多临床试验证实.     

Safety and survival outcomes for bloodless transplantation in patients with myeloma

High-dose therapy (HDT) and autologous stem cell transplantation (ASCT) are established components in the treatment of multiple myeloma; however, undergoing transplantation usually requires hematopoietic support, which poses a challenge among patients who are unwilling to receive blood products. Most transplant centers decline HDT/ASCT to these patients because of safety concerns. Here, the authors’ institutional data on safety, engraftment parameters, and survival outcomes after bloodless ASCT (BL-ASCT) are examined among patients with myeloma. This retrospective case-control study included patients who underwent BL-ASCT and Transfusion-supported ASCT (TS-ASCT) at Emory University Hospital between August 2006 and August 2016. In total, 24 patients who underwent BL-ASCT and 70 who underwent TS-ASCT were included. The median time for neutrophil engraftment, platelet engraftment and the median length of hospital stay all were equivalent for both groups. There were no transplant-related cardiovascular complications or mortality in either the BL-ASCT group or the TS-ASCT group. The median progression-free survival was 36 months and 44 months in the BL-ASCT and TS-ASCT groups, respectively (P = .277), and the median OS was not reached in either group at a median follow-up of 59 months after ASCT (P = .627). There was no transplant-related mortality at the 100-day or 1-year mark in either group. BL-ASCT is safe and feasible; transplant-related mortality, cardiovascular and hematologic complications are similar to those associated with TS-ASCT. Furthermore, BL-ASCT can yield similar engraftment and survival parameters comparable to those observed with TS-ASCT.     

Improved survival of multiple myeloma patients treated with autologous transplantation in the modern era of new medicine

New drugs for multiple myeloma (MM) have dramatically improved patients’ overall survival (OS). Autologous stem cell transplantation (ASCT) remains the mainstay for transplant-eligible MM patients. To investigate whether the post-ASCT prognosis of MM patients has been improved by new drugs, we undertook a retrospective observational analysis using the Transplant Registry Unified Management Program database in Japan. We analyzed 7323 patients (4135 men and 3188 women; median age, 59 years; range 16-77 years) who underwent upfront ASCT between January 2007 and December 2018. We categorized them by when they underwent ASCT according to the drugs’ introduction in Japan: group 1 (2007-2010), group 2 (2011-2016), and group 3 (2017-2018). We compared the groups’ post-ASCT OS. The 2-year OS rates (95% confidence interval [CI]) of groups 1, 2, and 3 were 85.8% (84.1%-87.4%), 89.1% (88.0%-90.1%), and 92.3% (90.0%-94.2%) (P < .0001) and the 5-year OS (95% CI) rates were 64.9% (62.4%-67.3%), 71.6% (69.7%-73.3%), and not applicable, respectively (P < .0001). A multivariate analysis showed that the post-ASCT OS was superior with these factors: age less than 65 years, performance status 0/1, low International Staging System (ISS) stage, receiving SCT for 180 days or less post-diagnosis, better treatment response pre-ASCT, later year of ASCT, and receiving SCT twice. A subgroup analysis showed poor prognoses for the patients with unfavorable karyotype and poor treatment response post-ASCT. The post-ASCT OS has thus improved over time (group 1 < 2 < 3) with the introduction of new drugs for MM. As the prognosis of high-risk-karyotype patients with ISS stage III remains poor, their treatment requires improvement.