造血干细胞移植治疗难治性多发性骨髓瘤

背景:近年来,多发性骨髓瘤发病率有所增长,然而治疗相当棘手。造血干细胞移植技术不断改进,新的药物应用于临床,以及移植联合新药治疗,为患者带来新的希望。目的:总结近年来造血干细胞移植及其与新药联用方案治疗难治性多发性骨髓瘤的新进展。方法:应用计算机检索PubMed、ISI平台BP+Medline数据库及万方、维普数据库1990年1月至2012年4月有关造血干细胞移植及免疫调节剂、蛋白酶体抑制剂联合移植的文献报道,排除陈旧的、内容重复的文章。结果与结论:检索及筛选后保存22篇中英文文献,并对其进行分析,得出造血干细胞移植以及联合新药的治疗策略使得大剂量化疗和自体干细胞移植治疗的效果得到显著改善。移植前加用新药诱导和移植后用新药维持治疗可以延缓进展期,提高总体生存率。异基因造血干细胞移植治疗可以使多发性骨髓瘤患者获得长期的分子生物学缓解并治愈。多种治疗方法的组合及优缺点比较,可更好的为临床医师在实践中根据患者实际情况进行决策,最大程度满足患者的需要。     

造血干细胞移植治疗难治性多发性骨髓瘤

背景：近年来,多发性骨髓瘤发病率有所增长,然而治疗相当棘手。造血干细胞移植技术不断改进,新的药物应用于临床,以及移植联合新药治疗,为患者带来新的希望。目的：总结近年来造血干细胞移植及其与新药联用方案治疗难治性多发性骨髓瘤的新进展。方法：应用计算机检索PubMed、ISI平台BP＋Medline数据库及万方、维普数据库1990年1月至2012年4月有关造血干细胞移植及免疫调节剂、蛋白酶体抑制剂联合移植的文献报道,排除陈旧的、内容重复的文章。结果与结论：检索及筛选后保存22篇中英文文献,并对其进行分析,得出造血干细胞移植以及联合新药的治疗策略使得大剂量化疗和自体干细胞移植治疗的效果得到显著改善。移植前加用新药诱导和移植后用新药维持治疗可以延缓进展期,提高总体生存率。异基因造血干细胞移植治疗可以使多发性骨髓瘤患者获得长期的分子生物学缓解并治愈。多种治疗方法的组合及优缺点比较,可更好的为临床医师在实践中根据患者实际情况进行决策,最大程度满足患者的需要。     

自体造血干细胞移植治疗多发性骨髓瘤

多发性骨髓瘤是浆细胞恶性增生性疾病,化疗能取得一定疗效,但完全缓解率低,维持时间短。目前,造血干细胞移植治疗已经成为重要的手段之一,并且取得了很大的进展。     

自体造血干细胞移植治疗多发性骨髓瘤

多发性骨髓瘤是浆细胞恶性增生性疾病，化疗能取得一定疗效，但完全缓解率低，维持时间短。目前，造血干细胞移植治疗已经成为重要的手段之一，并且取得了很大的进展。     

自体造血干细胞移植治疗多发性骨髓瘤

多发性骨髓瘤是一中老年恶性疾病，常规化疗效果差。大剂量化疗后辅以造血干细胞移植治疗效果较好，其中自体造血干细胞移植应用较多。本文推荐大剂量马法兰200mg/m^2。为预处理方案，未净化的自体外周血干细胞为造血干细胞来源。对移植后维持治疗、二次移植、预后因素等相关问题亦予以简介。     

硼替佐米为主的联合化疗方案加或不加造血干细胞移植治疗多发性骨髓瘤疗效分析

目的 观察以硼替佐米为主的联合化疗方案加或不加造血干细胞移植(SCT)治疗多发性骨髓瘤(multiple myeloma,MM)患者的疗效及不良反应.方法 31例初治或复发(难治)MM患者接受硼替佐米为主治疗.之后有6例患者接受SCT治疗.按照EBMT标准评价疗效,WHO标准判断不良反应.结果 ①有5例患者由于急性肾功能衰竭、肿瘤溶解综合征等原因终止治疗,其中3例死亡.可以统计疗效的26例患者共完成了99个疗程的治疗,总有效率(ORR)为80.8%.15例初治患者的ORR为100.0%.11例复发(难治)患者的ORR为54.6%.②15例初治患者中有7例完成了8个疗程的治疗,动态观察发现随着疗程的延长疗效不断提高.③6例初治患者化疗达完全缓解(CR)或接近CR(mCR)后行SCT治疗,其中1例复发,5例随访至移植后6～11个月仍持续CR.未采取SCT巩固的9例初治患者中除1例持续CR外有6例在停药后1～3个月复发或进展,2例失访.④多数治疗相关不良反应为l～2级,有3例患者因为末梢神经炎、窦性心动过缓等原因降低硼替佐米的用量,5例因严重不良反应终止治疗.结论 硼替佐米治疗初治及复发(难治)MM疗效肯定,但可能需要进行巩固治疗(如SCT)以维持疗效.硼替佐米不良反应多数轻微且可以耐受,但也应注意少见的严重不良反应.     

自体造血干细胞移植治疗多发性骨髓瘤

多发性骨髓瘤是一中老年恶性疾病,常规化疗效果差。大剂量化疗后辅以造血干细胞移植治疗效果较好,其中自体造血干细胞移植应用较多。本文推荐大剂量马法兰200mg/m~2为预处理方案,未净化的自体外周血干细胞为造血干细胞来源。对移植后维持治疗、二次移植、预后因素等相关问题亦予以简介。     

硼替佐米联合自体外周血造血干细胞移植治疗多发性骨髓瘤

本研究探讨硼替佐米联合自体外周血造血干细胞移植(APBSCT)治疗多发性骨髓瘤(MM)的疗效。对5例MM患者行自体外周血造血干细胞移植,在APBSCT前和预处理中以及移植后的维持治疗中均应用硼替佐咪治疗。选择预处理方案为:硼替佐米(bortezomib)+马法兰(melphalan)。输注的外周血单个核细胞(PBMNC)数为4.06×108(4.09×108-4.37×108)/kg,CD34+细胞数为3.98×106(2.49×106-8.2×106)/kg。结果表明:5例患者造血完全重建,中性粒细胞(ANC)大于0.5×109/L中位时间为14(13-25)天,Plt大于50×109/L中位时间为28(21-58)天。无移植相关死亡病例,5例患者均无病生存。结论:硼替佐米联合自体外周血造血干细胞移植是治疗MM的有效方法,移植后给予硼替佐米维持治疗可能是患者延长生存时间、提高生活质量的较好方法。     

自体造血干细胞移植治疗多发性骨髓瘤的研究进展

自体造血干细胞移植治疗多发性骨髓瘤的研究进展张茂宏孙恺综述自体造血干细胞移植（ＡＨＳＣＴ）包括自体骨髓移植（ＡＢＭＴ）和自体外周血干细胞移植（ＡＰＢＳＣＴ），自８０年代中期开始应用于血液系统恶性肿瘤包括多发性骨髓瘤（ＭＭ）的治疗。近年来的临床研究资料...     

造血干细胞移植治疗多发性骨髓瘤的研究进展

大剂量化疗加自体造血干细胞移植（AHSCT）能够使多发性骨髓瘤（MM）患者的完全缓解（CR）率和生存率明显提高，目前已逐渐成为65岁以下初治MM患者的标准治疗方法，然而复发率较高。高危组年轻患者行异基因造血干细胞移植（allo-HSCT）有可能治愈MM，由于移植相关死亡率高，尚不能作为MM患者常规治疗手段。非清髓及减低剂量的预处理造血干细胞移植，保留移植物抗骨髓瘤（GVM）效应，与AHSCT联合应用，可能进一步改善MM患者预后。     

新药时代自体造血干细胞移植在多发性骨髓瘤治疗中的问题与展望

自体造血干细胞移植(auto-HSCT)自20世纪80年代初开始应用于多发性骨髓瘤(MM)的治疗,一直在国际上被认为是年龄≤65岁初诊MM(NDMM)患者的首选或一线治疗选择。随着新药的不断涌现,MM的疗效得到很大的提高,auto-HSCT在MM治疗中的地位曾几度被质疑。auto-HSCT是一个整体治疗过程,auto-HSCT的每个环节也随治疗药物或手段的增加而发生了或多或少的改变。本文就新药时代auto-HSCT在MM治疗中的地位和进展作一综述。     

Cyclophosphamide‐based hematopoietic stem cell mobilization before autologous stem cell transplantation in newly diagnosed multiple myeloma

High‐dose cyclophosphamide (Cy) is frequently employed for peripheral blood mobilization of hematopoietic stem cells before high‐dose chemotherapy with autologous stem cell transplantation (ASCT) in multiple myeloma (MM). The benefit of mobilization with Cy over filgrastim (granulocyte colony‐stimulating factor; G‐CSF) alone is unclear. Between 2000 and 2008, 167 patients with newly diagnosed MM underwent single ASCT after melphalan conditioning at our institution. Seventy‐three patients were mobilized with G‐CSF alone, and 94 patients with Cy plus G‐CSF (Cy+G‐CSF). We retrospectively analyzed Cy's impact on both toxicity and efficacy. Mobilization efficiency was augmented by Cy; a mean total of 12 versus 5.8 × 10⁶ CD34+ cells/kg were collected from patients mobilized with Cy+G‐CSF versus G‐CSF, respectively, (P < 0.01), over a mean of 1.6 versus 2.2 days of peripheral blood apheresis (p = 0.001). Mobilization‐related toxicity was also, however, augmented by Cy; 14% of Cy+G‐CSF patients were hospitalized because of complications versus none receiving G‐CSF (P < 0.0001). Toxicity, including death, related to ASCT was similar between cohorts. Regarding long‐term outcomes, multivariate analysis revealed no difference for Cy+G‐CSF versus G‐CSF (hazard ratio 0.8 for event‐free survival [95% confidence interval {CI} 0.57–1.25] and 0.96 for overall survival [95% CI 0.61–1.54]). In summary, we show that mobilization with Cy increases toxicity without positively impacting long‐term outcomes in MM. Our findings place into question Cy's benefit as a routine component of stem cell mobilization regimens in MM. Randomized trials are needed to elucidate the risks and benefits of Cy more definitively. J. Clin. Apheresis 30:176–182, 2015. © 2014 Wiley Periodicals, Inc.     

The current status of hematopoietic stem cell transplantation for multiple myeloma

Multiple myeloma is often successfully controlled with conventional chemotherapy, but complete remissions are uncommon and cure is rare. High-dose therapy followed by autologous or allogeneic stem cells, employed for the treatment of multiple myeloma in the past 20 years, is promising as a means to increase remission rates and improve survival. Autologous transplants have not always demonstrated survival benefits in randomized studies because most of the patients transplanted relapse, while patients given conventional therapy can receive salvage transplants when they relapse. Efforts to improve the results of autologous transplant include targeted radiation, cytoprotective agents, tandem transplants, or post-transplant immunotherapy. Only allogeneic hematopoietic stem cell transplantation is potentially curative, due to a graft-versus-myeloma effect. While patients who receive either allogeneic or autologous stem cell transplants for multiple myeloma have similar 3-5 year survival, only allograft recipients appear to enjoy long-term disease-free survival. High transplant-related mortality associated with allogeneic stem cell transplantation is currently the major limitation to wider use of this potentially curative modality. Strategies designed to improve the therapeutic index of allografts include the use of nonablative conditioning regimens, peripheral blood cells rather than bone marrow, graft engineering, and targeted conditioning therapies such as bone-seeking radioisotopes.     

自体造血干细胞移植对多发性骨髓瘤患者预后的影响

目的 探讨自体造血干细胞移植(ASCT)在多发性骨髓瘤(MM)治疗中的地位以及对预后的影响.方法 回顾分析1998年10月至2007年2月接受ASCT治疗的28例MM患者(A组)的临床和随访资料,并与同期未行ASCT的MM患者,包括接近完全缓解(nCR)或以上缓解的23例(B组)和仅获得部分缓解(PR)的25例(C组)患者进行比较.分析 ASCT对缓解程度的影响并采用Kaplan-Meier法比较3组患者的缓解持续时间(DOR)、疾病进展时间(TTP)和生存(OS)时间.结果 移植前未达到nCR的8例患者[7例PR和1例轻微缓解(MR)]移植后均达到nCR或以上缓解(3例CR,5例nCR),A组完全缓解(CR)率由移植前的10.7%(3例)提高到42.9%(12例).A组中位DOR(33个月)较B组(17个月)和C组(18个月)延长,差异有统计学意义;A组中位TTP(45个月)较C组(28个月)延长,差异有统计学意义,但与B组(43个月)无明显差异;中位随访时间为30(4～79)个月,A组和B组OS时间较C组长,但随访结束时未显示出差异有统计学意义.结论 ASCT可进一步增强患者的缓解程度,延长患者的DOR和TTP,并可能延长OS时间,改善生存质量;ASCT对TTP的延长得益于更好程度的缓解,因此对其他治疗不能达到很好缓解的MM患者可以通过ASCT改善预后.     

Assessing the charges associated with hematopoietic stem cell mobilization and remobilization in patients with lymphoma and multiple myeloma undergoing autologous hematopoietic peripheral blood stem cell transplantation

BACKGROUND: The purpose of this study was to perform a detailed analysis of the charges associated with chemomobilization and remobilization of autologous hematopoietic stem cells (HSCs) and to quantify medical costs and resource utilization associated with these procedures. STUDY DESIGN AND METHODS: Patients with lymphoma underwent chemomobilization with ifosfamide and etoposide with or without rituximab (IE ± R). Patients with multiple myeloma (MM) received a modified hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone (hyper‐CVAD) regimen after failing to mobilize with growth factors only. RESULTS: Between January 2004 and October 2006, 98 patients with lymphoma underwent HSC mobilization with IE ± R. Mobilization with IE ± R was effective, with 90.8% of patients collecting at least 2 × 10⁶ CD34+ cells/kg. The total charges for treatment were $27,996 and $37,667 for patients mobilized with IE and IE + R, respectively. Hospital readmission for complications occurred in 26.5% of patients, resulting in additional charges of $10,356. The preapheresis procedure charge was estimated to be $2522, the charge for a 2‐day apheresis session was $5160, and the postapheresis phase resulted in charges of $8040. Our analysis determined that reducing apheresis by 1 day has the potential to save $6600. We also performed a retrospective analysis of 16 patients with MM remobilized with a modified hyper‐CVAD regimen. Remobilization was successful, with 87.5% of patients. Our analysis determined that mobilization, preapheresis, apheresis, and postapheresis phase charges were $24,968, $2522, $6158, and $12,060, respectively. CONCLUSIONS: Optimization of HSC mobilization regimens to reduce failure rates would not only benefit patients but also reduce the overall medical costs.     

Role of stem cell transplantation in treatment of multiple myeloma

The role of stem cell transplantation in the treatment of multiple myeloma (MM) is described. High-dose chemotherapy (HDT) followed by autologous stem cell transplantation (SCT) is routinely recommended for most patients with newly diagnosed MM under 65 years of age. However, recently published meta-analysis of randomized controlled trials indicated PFS benefit but not OS benefit for HDT with autologous SCT performed early in MM. Tandem autologous SCT is superior to single transplantation in terms of event-free survival. Survival in recipients of autologous SCT followed by reduced-intensity conditioning allogeneic transplantation is superior to that in recipients of tandem autologous SCT. Recently developed new drugs including thalidomide, lenalidomide or bortezomib in combination with SCT might improve survival of myeloma patients.     

Characteristics of unexpected protein bands in multiple myeloma patients after autologous stem cell transplantation

ObjectivesThe aim of this study is to investigate the characteristics of unexpected protein bands (UPBs) in patients with multiple myeloma (MM).Design and methodsIndividuals diagnosed with MM (n = 193) were enrolled. Their medical records and IFE patterns were reviewed.ResultsOf the patients that underwent ASCT, 54% developed UPBs. The median time for UPB appearance and duration was 1.8 and 5.7 months, respectively. IFE revealed 74.1% of UPBs to be of the immunoglobulin G type and 72.2% to be of the κ-type. At UPB appearance, 42.6% of patients were defined as sCR or CR, and 50.0% of the patients satisfying the CR criteria had an abnormal FLC ratio. Of the patients who developed UPBs, five relapsed. Among these, four patients showed disappearance of the previous IFE oligoclonality and reappearance of the original paraprotein at relapse.ConclusionsClose follow-up of UPBs is critical for evaluating MM therapeutic response and disease progression. The presence of monoclonal bands may indicate relapse of disease, but in the vast majority of cases with UPBs, it does not; instead, it most likely represents a transient phenomenon caused by the immune response.     

Immune reconstitution after autologous hematopoietic stem cell transplantation

Autologous hematopoietic stem cell transplantation has proved to be an effective treatment for certain hematologic malignancies. However, relapse rates are high during the first year after transplantation. These relapses are attributed to the failure of high-dose chemotherapy to eradicate minimal residual malignant disease. In allogeneic hematopoietic stem cell transplantation, the higher antitumor effects observed compared with those in autologous hematopoietic stem cell transplantation are based on the immunologically mediated graft-vs-tumor effect. Therefore, a better understanding of the mechanisms involved in immune reconstitution after hematopoietic stem cell transplantation may clarify the importance of various components of the recovery of the immune system as they pertain to eradication of residual tumor, as well as uncover possible interventions directed at maximizing this effect. This review focuses on immune reconstitution after autologous hematopoietic stem cell transplantation. Autologous hematopoietic stem cell transplantation is not affected by graft-vs-host disease or immunosuppressive therapy after transplantation to control graft-vs-host disease, providing a direct insight into the mechanisms involved in immune reconstitution after engraftment.