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。     

自体造血干细胞移植治疗多发性骨髓瘤的现状与展望

自体骨髓移植治疗多发性骨髓瘤(MM)始于20世纪80年代.随着自体外周血干细胞移植替代骨髓移植,大大提高了自体造血干细胞移植治疗MM的可行性.多个历史对照和随机临床研究显示自体造血干细胞移植较传统化疗显著地提高MM患者治疗的反应率、完全缓解率、无事件生存和(或)总生存,而治疗反应程度与生存相关.自体造血干细胞移植在欧美国家已成为年轻、适合(年龄≤65岁、肾功能正常和一般状况良好)的MM患者的一线标准治疗.同时已证实美法仑200mg/m2是预处理的最佳方案.双次移植有可能进一步提高治疗反应、无事件生存和(或)总生存,特别是对首次移植后未获得非常好的部分缓解或接近完全缓解的患者.近10年来,随着免疫调节药物沙利度胺及其衍生物和蛋白酶体抑制剂硼替佐米等新型抗MM药物的应用.显著提高了化疗的反应率和缓解率.目前尚无证据显示新药可以替代自体造血干细胞移植,但这些药物在移植前后的应用,进一步提高了MM的疗效.     

骨髓增生异常综合征和再生障碍性贫血患者异基因造血干细胞移植的时机选择:第56届美国血液学会年会报道

介绍第56届美国血液学会(ASH)年会关于骨髓增生异常综合征(MDS)和再生障碍性贫血(AA)患者进行异基因造血干细胞移植的时机选择的报道.同种异体造血干细胞移植(HSCT)治疗MDS是疾病治愈的有效途径,但病死率也很高.对于低危和中危-Ⅰ MDS患者,应尽量延后HSCT的应用时间.但是对中危-Ⅱ和高危MDS患者,在确诊后应尽快进行HSCT,其生存期明显优于延后HSCT的患者.HSCT前的预处理方案可以选择阿扎胞苷、白血病形式的诱导化疗或联合以上2种治疗.HSCT已被证实可以治愈重型AA,但新诊断的患者中HLA相合的同胞供者仅占1/4.总之,HLA匹配的相关和无关供者HSCT会成为大多数高危MDS和初发重型AA的治疗选择.     

造血干细胞移植治疗多发性骨髓瘤的研究进展

 【摘要】　造血干细胞移植（HSCT）是治疗多发性骨髓瘤（MM）的一线方案。自体造血干细胞移植（auto-HSCT）可提高患者缓解率,延长生存期。首次auto-HSCT后,未获得非常好的部分缓解及以上疗效的患者,可行二次auto-HSCT进一步改善疗效。异基因造血干细胞移植（allo-HSCT）具有治愈MM的潜能,但移植相关死亡率高,患者生存并未获益。减低剂量的allo-HSCT相关死亡率低,但复发率高,也未显示出生存优势。序贯auto-HSCT及allo-HSCT也未使患者生存明显获益。总结近期HSCT的研究进展。     

自体造血干细胞移植治疗多发性骨髓瘤的现状与展望

 自体骨髓移植治疗多发性骨髓瘤（MM）始于20世纪80年代。随着自体外周血干细胞移植替代骨髓移植,大大提高了自体造血干细胞移植治疗MM的可行性。多个历史对照和随机临床研究显示自体造血干细胞移植较传统化疗显著地提高MM患者治疗的反应率、完全缓解率、无事件生存和（或）总生存,而治疗反应程度与生存相关。自体造血干细胞移植在欧美国家已成为年轻、适合（年龄≤65岁、肾功能正常和一般状况良好）的MM患者的一线标准治疗。同时已证实美法仑200 mg／m2是预处理的最佳方案。双次移植有可能进一步提高治疗反应、无事件生存和（或）总生存,特别是对首次移植后未获得非常好的部分缓解或接近完全缓解的患者。近10年来,随着免疫调节药物沙利度胺及其衍生物和蛋白酶体抑制剂硼替佐米等新型抗MM药物的应用,显著提高了化疗的反应率和缓解率。目前尚无证据显示新药可以替代自体造血干细胞移植,但这些药物在移植前后的应用,进一步提高了MM的疗效。     

造血干细胞移植的临床进展

 异基因造血干细胞移植（allo-HSCT）是治愈恶性血液病、重型再生障碍性贫血和遗传性血液病的重要方法,近年造血干细胞移植（HSCT）在诸多方面都取得了重要及深刻的发展,就al-lo-HSCT在血液病治疗体系中的地位、单体型HSCT、非血缘供体HSCT、非清髓性HSCT和脐血HSCT的策略以及临床移植免疫研究领域的相关进展进行了阐述。     

多发性骨髓瘤的维持治疗:有最佳药物或药物组合吗?

多发性骨髓瘤(MM)是一种常见的血液系统恶性肿瘤,新药的应用及自体造血干细胞移植等显著提高了MM的反应率,但由于无法根除微小残留病,患者最终难免复发.维持治疗有望保持甚至提高缓解深度,进而延长MM患者的无进展生存和总生存时间.     

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。     

造血干细胞移植治疗血液系统恶性肿瘤3例

造血干细胞移植(HSCT)包括自体HSCT和异基因HSCT，是近年来血液学重大进展的领域，发展极为迅速，目前已成为治愈恶性血液病最有效的方法，我院自1997年8月至今对2例恶性淋巴瘤(ML)患者分别予自体骨髓移植……     

靶向新药时代自体造血干细胞移植在多发性骨髓瘤治疗中的作用

多发性骨髓瘤（MM）是浆细胞恶性克隆性疾病,自体干细胞移植（ASCT）的加入,增加了大剂量化疗在MM治疗中的优势,使部分患者达到长期生存.即使在靶向新药时代ASCT仍可以明显提高治疗的反应率.靶向新药在ASCT前后联合应用,可辅助提高ASCT的疗效,这是目前使用靶向新药的趋势,但其仍不能取代ASCT在MM治疗中的地位.研究更为合理、有效、低毒的治疗方案是今后的方向.     

High-risk multiple myeloma: does it still exist?

Major improvement milestones in the treatment of patients with multiple myeloma (MM) include the introduction of the melphalan/prednisone combination in the 1960s, high-dose chemotherapy supported by autologous stem cell transplant in the 1980s, and the more recent introduction of the novel agents thalidomide, lenalidomide, and bortezomib. Historically, age and eligibility for autologous stem cell transplantation were the primary basis for treatment selection, but, from a biologic standpoint, MM therapy was "one size fits all," in that therapy was not tailored based on molecular or other features that define subtypes of MM. Recently, novel therapies have extended overall survival for the broad spectrum of patients with myeloma. Moreover, newer data demonstrate that novel therapies may ameliorate the prognostic impact of predictors of high risk and poor outcome in MM, which suggests that patients with MM and with high-risk disease should receive novel agents. Such approaches may constitute nascent steps toward individualized therapy, ie, the selection of highly effective therapies based on specific features exhibited by an individual patient's MM. However, prospective data that demonstrate the validity of these approaches are lacking. Definitive, multi-institutional clinical trials are required before redefining standards of myeloma care based on this approach.     

Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma: What Place, If Any?

Despite the curative potential of allogeneic hematopoietic stem cell transplantation (allo HSCT) for patients with multiple myeloma (MM) and reduction of transplant-related mortality with non-myeloablative transplant approaches, the role of this treatment modality in the care of MM patients remains controversial. This controversy is due to the conflicting data emerging from the large cooperative group trials as well as the improvement in outcomes that has been seen with proteosome inhibitors, new immune modulatory drugs as well as the use of post-transplant maintenance therapy. For an individual patient, the risk benefit ratio of allografting remains uncertain. We review the current data and provide recommendations on where and how allo HSCT for myeloma should be further explored.     

Is there still a role for stem cell transplantation in multiple myeloma?

High-dose chemotherapy and autologous stem cell transplantation (ASCT) are a standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (MM). The introduction of novel agents, which range from immunomodulatory drugs and proteasome inhibitors to monoclonal antibodies and have now been integrated into both induction and salvage regimens, has dramatically revolutionized the treatment landscape of MM and challenged the role of high-dose chemotherapy and ASCT in treating MM. These advances have led to a number of provocative questions. First, what is the current role of stem cell transplantation (SCT) in comparison with standard-dose therapy incorporating novel agents? Second, should ASCT be performed upfront (“early”) or later (“delayed”) in the course of the disease? Third, should single or double ASCT be performed? Fourth, is allogeneic SCT still an option for patients with MM? This article provides an overview of available data and evidence-based responses regarding the role of SCT in MM.     

硼替佐米联合沙利度胺和地塞米松方案序贯造血干细胞移植治疗初治多发性骨髓瘤的临床观察

目的探讨硼替佐米联合方案序贯造血干细胞移植治疗初治多发性骨髓瘤的疗效和相关毒副作用。方法选取2006年6月至2014年4月初治多发性骨髓瘤33例为研究对象,采用硼替佐米+沙利度胺+地塞米松(BTD)方案诱导治疗(2⁷个疗程),其中14例继以马法兰预处理后行造血干细胞移植;所有患者均接受沙利度胺+地塞米松(TD)或来那度胺+地塞米松(LD)方案维持治疗。随访57个疗程),其中14例继以马法兰预处理后行造血干细胞移植;所有患者均接受沙利度胺+地塞米松(TD)或来那度胺+地塞米松(LD)方案维持治疗。随访5⁹2个月,观察疗效及不良反应。结果 BTD方案诱导治疗后获得完全缓解(CR)、很好的部分缓解(VGPR)、部分缓解(PR)的例数分别为8例(24.2%)、11例(33.3%)、12例(36.4%),总有效率(ORR)为94.0%。14例移植患者中,移植后获VGPR 9例,单用BTD组和序贯移植组的中位随访时间分别为51和32个月,中位生存时间尚未获得,预期3年无进展生存率分别为42.3%和58.7%。BTD方案的不良反应主要为血细胞减少、周围神经病变、带状疱疹病毒感染、便秘、感染和乏力等,大多数患者给予对症治疗后可耐受。结论以硼替佐米联合诱导治疗并以造血干细胞移植序贯治疗多发性骨髓瘤,毒副反应可耐受,疗效显著,生存期较长。     

Controversies in Multiple Myeloma: to Transplant or Not?

The treatment of multiple myeloma (MM) has dramatically changed in the last decade due to the introduction of the immunomodulatory drugs (IMIDs) and proteasome inhibitors, otherwise known as the novel agents. Prior to the advent of the novel agents, the gold standard of treatment had been high-dose chemotherapy with autologous stem cell transplantation (HDT/ASCT) for eligible candidates. Given the remarkable activity of the novel agents, and the significant morbidity of HDT/ASCT, the role of stem cell transplantation has now come into question. In this review, we explore the benefits and drawbacks to HDT/ASCT in the era of the novel therapies.     

State of the art therapy in multiple myeloma and future perspectives

Treatment for multiple myeloma (MM) has changed beyond recognition in the past decades. While until the early 1980s, MM caused a slow progressive decline in quality of life until death after about two years, today's patients can expect a 50% chance of achieving a complete remission, a median survival time of five years and a 20% chance of surviving longer than ten years. State of the art therapy comprises: evidence-based supportive care; highly effective and well tolerated chemotherapeutic regimens; and for patients qualifying for intensive high-dose conditioning, autologous haematopoietic stem cell transplantation (HSCT) is an option. Maintenance therapy has become increasingly important since a majority of patients is able to achieve a good remission after front-line therapy which is aimed to be preserved as long as possible. In addition, improved understanding of the disease biology has led to the development of novel biological treatment agents, such as thalidomide, bortezomib and others, targeted at cellular mechanisms and interactions, e.g. with the bone marrow microenvironment. These strategies are incrementally integrated into modern MM care. This review considers recent clinical advancements in anti-myeloma strategies and provides an overview of the state of the art management of MM patients.     

新药时代自体造血干细胞移植在多发性骨髓瘤中的应用前景*

自体干细胞移植（ASC T）在传统化疗时代已成为65岁以下初诊多发性骨髓瘤（MM）的标准一线治疗。随着新型靶向药物为基础的化疗在诱导、巩固和维持治疗阶段的广泛应用，MM的缓解率得到显著提高，因此是否需要ASCT成为了新药时代关注的焦点。目前现有的资料仍然支持ASCT是符合条件的初诊MM患者的一线治疗，新药作为ASCT前诱导治疗以及ASCT后巩固、维持治疗有助于进一步提高缓解率，延长无进展生存时间。但今后仍需要开展更多前瞻性临床试验进一步明确ASCT在MM中的作用、进一步优化治疗方案，以期实现MM治愈的目标。