偏小剂量的硼替佐米联合地塞米松治疗初发多发性骨髓瘤疗效观察

目的每次1.75 mg(0.8～1.0 mg/m2)的硼替佐米联合地塞米松对初发多发性骨髓瘤疗效观察。方法17例初发患者接受硼替佐米+地塞米松的方案治疗。硼替佐米每次1.75 mg(0.8～1.0 mg/m2),第1、4、8、11天,3～5秒内静脉推注完成;地塞米松20 mg/d,第1、2、4、5、8、9、11、12天静脉滴注,同时地塞米松0.75mg/d,口服,第1～12天。21天为1个疗程。完成4个疗程。结果完成4个疗程偏小剂量硼替佐米结合地塞米松治疗的初发多发性骨髓瘤患者的有效率为88.23%。高于传统VAD化疗方案的有效率(44.74%),且两者有统计学差异;不低于推荐剂量(1.3 mg/m2)的硼替佐米方案治疗的有效率。结论偏小剂量硼替佐米联合地塞米松对初发多发性骨髓瘤治疗仍有较好疗效,但其对疗效维持的长久性尚需进一步随访观察。     

新诊断多发性骨髓瘤的危险分层治疗:来自2012年美国临床肿瘤学会年会的报道

 【摘要】多发性骨髓瘤具有较大的异质性,根据危险分层对患者进行治疗具有重要意义。根据细胞遗传学异常可将患者分为标危、中危和高危3组。标危患者可采用4周期的Rd(来那度胺＋地塞米松)或VCD(硼替佐米＋环磷酰胺＋地塞米松)的方案进行诱导治疗;中危患者可采用4周期的VCD(硼替佐米＋环磷酰胺＋地塞米松)的方案进行诱导治疗;高危患者可采用4周期的VRD(硼替佐米＋来那度胺＋地塞米松)的方案进行诱导治疗。诱导治疗结束后,可进行自体造血干细胞移植或巩固维持治疗。患者年龄、一般状况和合并症是决定是否适合自体造血干细胞移植的关键因素。     

硼替佐米治疗多发性骨髓瘤八例

 目的　初步观察硼替佐米联合地塞米松（DEX）或化疗治疗多发性骨髓瘤（MM）的初步疗效和患者的不良反应。方法　8例 MM患者分别采用硼替佐米（1.3 mg／m2,第1、4、8、11天或3.5 mg,第1、8天）联合地塞米松或VTD[长春新碱（VCR）、吡柔比星（THP）、Dex]方案治疗,每4周为1个疗程,完成1～4个疗程,其中3例行自体外周血造血干细胞移植,评价疗效和不良反应。结果　3例完全缓解（CR）,2例部分缓解（PR）,3例达到微小反应（MR）;总有效（CR+PR）率为62.5 %;常见不良反应有胃肠道反应、白细胞和血小板轻度减少、肢端麻木感、肝功能异常及乏力等,均能耐受。3例行自体外周血造血干细胞移植（APBSCT）患者获得足量的干细胞数并成功植活。结论　硼替佐米联合DEX或化疗治疗 MM疗效好,不良反应轻微,患者易于耐受,硼替佐米不影响MM干细胞采集和植活。     

硼替佐米治疗多发性骨髓瘤八例

目的 初步观察硼替佐米联合地塞米松(DEX)或化疗治疗多发性骨髓瘤(MM)的初步疗效和患者的不良反应.方法 8例MM患者分别采用硼替佐米(1.3 mg/m2,第1、4、8、11天或3.5mg,第1、8天)联合地塞米松或VTD[长春新碱(VCR)、吡柔比星(THP)、Dex]方案治疗,每4周为1个疗程,完成1～4个疗程,其中3例行自体外周血造血干细胞移植,评价疗效和不良反应.结果3例完全缓解(CR),2例部分缓解(PR),3例达到微小反应(MR);总有效(CR+PR)率为62.5%;常见不良反应有胃肠道反应、白细胞和血小板轻度减少、肢端麻木感、肝功能异常及乏力等,均能耐受.3例行自体外周血造血干细胞移植(APBSCT)患者获得足量的干细胞数并成功植活.结论 硼替佐米联合DEX或化疗治疗MM疗效好,不良反应轻微,患者易于耐受,硼替佐米不影响MM干细胞采集和植活.     

硼替佐米联合左旋苯丙氨酸氮芥预处理自体干细胞移植治疗多发性骨髓瘤三例

 【摘要】　目的　观察硼替佐米联合左旋苯丙氨酸氮芥为预处理方案进行自体外周血造血干细胞移植（APBSCT）治疗多发性骨髓瘤（MM）患者的疗效及安全性。方法　对3例MM患者诱导治疗缓解后行APBSCT。预处理方案均采用硼替佐米（1.3 mg／m2,－6、－3、+1、+4天）+左旋苯丙氨酸氮芥（200 mg／m2,－2天）。观察治疗后造血重建、并发症及安全性,并进行疗效评价。结果　3例患者移植后造血均快速重建。预处理后不良反应主要表现为恶心、呕吐、乏力、四肢麻木、中性粒细胞及血小板减少等,均经对症治疗后好转。移植后3个月均达完全缓解（CR）,随访期内无复发,患者均无进展生存。结论　采用硼替佐米+左旋苯丙氨酸氮芥预处理进行APBSCT,患者CR率高、无事件生存期长、安全性好,优于传统预处理方案。     

以硼替佐米为基础的联合化疗序贯自体外周血造血干细胞移植治疗原发性浆细胞白血病一例并文献复习

目的：探索以硼替佐米为基础的联合化疗序贯自体外周血干细胞移植治疗原发性浆细胞白血病（pPCL）的效果。方法报道1例经硼替佐米为基础的联合化疗序贯自体外周血干细胞移植治疗pPCL,并进行相关文献复习。结果该例患者经硼替佐米为基础的联合化疗达到非常好的部分缓解（VGPR）,进行自体外周血干细胞移植后达到完全缓解（CR）,无进展生存达33个月。结论以硼替佐米为基础的联合化疗及自体造血干细胞移植可能会改善pPCL患者的预后,减少复发。     

多发性骨髓瘤固定周期治疗和连续治疗的研究进展

多发性骨髓瘤(MM)占血液系统恶性肿瘤的13％,常发生于老年人群.新药物和治疗方法的引入使患者的生存期显著延长,但是患者在不同治疗阶段仍会复发.有研究证实,在行自体造血干细胞移植的患者中,应用来那度胺、硼替佐米或硼替佐米联合方案巩固治疗,可提高标危或高危患者的无疾病进展生存期;在不适合移植的患者中,应用来那度胺联合地塞米松方案连续治疗的患者,比应用美法仑联合泼尼松、沙利度胺方案固定周期治疗的患者生存期长,优化治疗方案是目前合适的选择.文章对移植后及不适合移植患者的固定周期治疗和连续治疗的效果进行介绍.     

VD方案联合自体造血干细胞移植治疗难治性不分泌型多发性骨髓瘤一例并文献复习

 目的　观察硼替佐米+地塞米松（VD）方案联合自体造血干细胞移植（ASCT）治疗一例难治性不分泌型多发性骨髓瘤（MM）患者的疗效。方法　通过对1例难治性不分泌型MM患者给予VD方案化疗4个周期,在疾病得到有效控制、临床体征改善后,进行ASCT（预处理方案为美法仑200 mg／m2）,并对国内外相关文献复习。结果　患者经过化疗达到接近完全缓解（nCR）,之后联合ASCT后达到完全缓解（CR）。结论　VD方案联合ASCT可明显改善难治性不分泌型MM患者的临床预后。     

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。     

硼替佐米治疗难治性复发性多发性骨髓瘤疗效分析

 目的　探讨硼替佐米联合地塞米松治疗难治性复发性多发性骨髓瘤（MM）的临床疗效及不良反应。方法　硼替佐米1.3 mg／m2静脉注射第1、4、8、11天,地塞米松20 mg／d,第1天至第4天,第8天至第11天,第17天至第20天静脉滴注,21 d为1个周期,双周期时,地塞米松20 mg／d,第1天至第4天。结果　经4～6个周期治疗,3例完全缓解,4例接近完全缓解,3例部分缓解。结论　硼替佐米联合地塞米松治疗难治性复发性MM是较好的选择。     

T - VAD 方案联合自体外周血造血干细胞移植治疗多发性骨髓瘤的疗效观察

目的：观察 T - VAD 方案联合自体外周血造血干细胞移植（ autologous peripheral blood hematopoietic stem cells，APBSC）治疗多发性骨髓瘤（multiple myeloma，MM）的临床疗效及不良反应。方法：选取2010年1月-2014年12月采用 T - VAD 方案联合自体外周血造血干细胞移植治疗的30例多发性骨髓瘤患者的临床资料进行回顾性研究。T - VAD 方案：沙利度胺起始剂量为50mg/晚，每周增加50～100mg/晚，最大剂量200mg/晚，若无明显不适，持续服用。长春新碱0.4mg/ d，静脉滴注，第1～4d；多柔比星10mg/（m2·d），静脉滴注，第1～4d；地塞米松40mg/ d，静脉滴注，第1～4d，第9～12d，28d 为一个疗程，共4个疗程。T - VAD 方案4个疗程诱导治疗后给予自体外周血造血干细胞采集、移植术。结果：患者移植术后，造血功能均顺利重建，无移植相关的死亡发生。30例患者在移植后3个月，完全缓解10例（33.3%），高质量缓解（非常好的部分反应，VGPR）16例（53.3%），部分反应2例（6.6%），无变化2例（6.6%）。不良反应主要有不同程度的恶心、呕吐、脱发及骨髓抑制等。结论：T - VAD 联合自体外周血造血干细胞移植治疗多发性骨髓瘤疗效明显，患者耐受性好。     

Bortezomib (Velcade) for progressive myeloma after autologous stem cell transplantation and thalidomide

Twenty-one patients with multiple myeloma, all relapsed after frontline autologous stem cell transplantation and all relapsed again after or resistant to thalidomide (employed as second line treatment) received bortezomib (1.3 mg/m(2) body surface twice weekly for 2 weeks followed by an interval of 10-12 days) without adjunct of steroids as third line therapy. Three patients died of progressive disease during the first 2 cycles with bortezomib. Eighteen patients received at least 2 cycles and were evaluated for response. According to EBMT criteria, two complete (negative immunofixation) and seven partial (reduction of M-component > 50-75%) remissions were achieved (ITT response rate 42.8%). Duration of response lasted from 2 to 14+ months. Grades 3-4 toxicities (thrombocytopenia, leucopenia, peripheral neuropathy and vasculitis) were observed in seven patients, but no patient interrupted the treatment due to side effects. We conclude that bortezomib alone may induce high quality responses as third line salvage therapy with acceptable toxicity in a significant proportion of homogeneously pre-treated myeloma patients with progressive disease after autologous transplantation and thalidomide.     

Bortezomib-induced pneumonitis during bortezomib retreatment in multiple myeloma

Bortezomib is a proteasome inhibitor and is active against multiple myeloma. Most toxicities associated with bortezomib are mild to moderate and manageable; however, bortezomib-induced pneumonitis has been reported in some multiple myeloma cases. Bortezomib-induced pneumonitis was reported to occur relatively soon after the first administration of bortezomib. A 64-year-old Japanese man with multiple myeloma received low-dose dexamethasone followed by bortezomib monotherapy as the initial therapy. He had no pulmonary complications during bortezomib treatment. Thereafter, he was treated with high-dose chemotherapy, followed by autologous peripheral blood stem cell transplantation. Ten months after autologous peripheral blood stem cell transplantation, his disease relapsed and he received bortezomib retreatment. On the fifth day after the second dose of weekly bortezomib, he complained of mild dyspnea, dry cough and fever. High-resolution computed tomography of the chest showed bilateral infiltrates with partial ground glass appearance in the lower lobes. The diagnosis of bortezomib-induced pneumonitis was made. His bortezomib-induced pneumonitis responded to steroid therapy and his respiratory symptoms disappeared. This is the first report in which bortezomib-induced pneumonitis occurred during bortezomib retreatment for relapsed multiple myeloma. Careful management is needed during bortezomib retreatment, even after the previous course of bortezomib was administered safely.     

Combination chemotherapy with bortezomib, cyclophosphamide and dexamethasone may be effective for plasma cell leukemia

Plasma cell leukemia is a rare malignant plasma cell disorder characterized by proliferation of plasma cells in blood and the bone marrow, the outcome of which is poor with conventional therapy. More effective treatment strategies are therefore needed for this disorder. Here, we report a case of secondary plasma cell leukemia from Immunoglobulin D multiple myeloma refractory to doxorubicin-containing chemotherapy and thalidomide. The patient achieved complete remission with bortezomib-containing chemotherapy as follows: bortezomib 1.3 mg/m2 intravenous infusion on days 1, 4, 8 and 11; cyclophosphamide 750 mg/m(2) intravenous infusion on days 1 and 3; dexamethasone 40 mg/m2 intravenous infusion on days 1-4. Complete remission was maintained until the fourth course of the treatment, and we then performed autologous peripheral blood stem cell transplantation. Our experience suggests that combination chemotherapy with bortezomib, cyclophosphamide and dexamethasone may be an effective induction treatment for plasma cell leukemia.     

KD-PACE Salvage Therapy for Aggressive Relapsed Refractory Multiple Myeloma,Plasma Cell Leukemia and Extramedullary Myeloma

BackgroundPatients with advanced/aggressive multiple myeloma have limited treatment options to achieve rapid disease control. In eligible patients, bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide is often used. However, many patients are refractory to or have toxicities from bortezomib and there is a need for bridging therapy. We have used a modified regimen incorporating the second-generation proteasome inhibitor carfilzomib (carfilzomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide and etoposide [KD-PACE]) instead of bortezomib for relapsed/refractory multiple myeloma.Patients and MethodsThis 2-center retrospective study included consecutive patients receiving KD-PACE for relapsed or refractory multiple myeloma, plasma cell leukemia, or extramedullary myeloma. The primary outcome was the feasibility of KD-PACE as a bridging therapy to a more definitive treatment option.ResultsFifty-two patients were included. The median age was 57 years, and 67% were male. Thirty-one patients were bridged with KD-PACE to autologous hematopoietic stem cell transplant (29%), allogenic hematopoietic stem cell transplant (27%), or a clinical trial (12%). Patients bridged to autologous hematopoietic stem cell transplant, allogenic hematopoietic stem cell transplant, or a clinical trial had a superior progression-free survival (8.3 months vs 2.3 months in the nonbridged group; P < .001) and overall survival (median, 16.7 months vs 4.3 months in the nonbridged group; P < .001). No unexpected toxicities occurred from the treatment regimen.ConclusionKD-PACE is a promising treatment option for select patients with advanced/aggressive forms of myeloma requiring rapid disease control before a more definitive salvage therapy such as auto/allotransplantation or a clinical trial.     

Management of multiple myeloma with bortezomib: experts review the data and debate the issues

Cure for multiple myeloma is rare; the success of treatment is measured by response, and length of remissions and survival. Initial treatment for patients young and fit enough is high-dose chemotherapy with autologous stem cell transplantation. Various chemotherapy regimens are employed as initial therapy in patients who cannot withstand the autologous stem cell transplantation regimen, and for treatment of refractory or relapsed disease. Commonly used agents either alone or in combination have included dexamethasone, vincristine, doxorubicin, melphalan, cyclophosphamide, etoposide, cisplatin and, more recently, thalidomide. Within the past few years, the first-in-class proteasome inhibitor bortezomib has been introduced for the treatment of relapsed multiple myeloma with data demonstrating efficacy and safety. Throughout Europe, a faculty of experts conducted a series of debates with over 450 clinicians to discuss the efficacy of bortezomib vis-à-vis other available therapies. Of primary concern was the place of bortezomib in maximizing efficacy throughout the course of the disease and treatment by increasing response rates and improving duration of response, while maintaining an acceptable level of toxicity. The experts concluded that bortezomib, with its unique mechanism of action and demonstrated clinical efficacy and safety, should be considered as standard, early treatment in patients with relapsed multiple myeloma, especially after first relapse.     

大剂量化疗联合自体移植治疗复发髓母细胞瘤1例并文献复习

目的:探讨大剂量化疗联合自体移植治疗复发髓母细胞瘤的疗效。方法:报告1例大剂量化疗联合自体移植成功治疗复发髓母细胞瘤的经验,并结合文献复习进行分析。结果:患者使用大剂量化疗联合自体移植,术后35个月,疾病无进展、无复发。结论:大剂量化疗联合自体造血干细胞移植治疗复发髓母细胞瘤疗效优于常规化疗,值得进一步临床应用和推广。     

PAD序贯自体造血干细胞移植治疗难治多发性骨髓瘤(附22例)

目的:多发性骨髓瘤(multiple myeloma,MM)至今仍不可治愈,几乎所有病人均会出现复发或难治,本文初步探讨硼替佐米应用于难治性MM患者PAD化疗并序贯自体外周血造血干细胞移植(autologous pe-ripheral blood stem cell t ransplantation,APBSCT)的可行性和疗效。方法:采用PAD(硼替佐米+阿霉素+地塞米松)方案治疗复发或难治性MM。结果:22例中3例难治MM患者给予PAD方案化疗4-6个疗程后,2例达到接近完全缓解(nCR),1例达到部分缓解(VGPR),并随后行APBSCT,动员方案PAD+CTX(PAD,环磷酰胺1.5g/m2,d15)联合G-CSF。预处理方案为马法兰140mg/m2。移植后采用沙利度胺100mg/天。所有患者在移植前均达到CR或VGPR,干细胞采集充分,安全有效,移植后造血功能均快速顺利重建。无1例死亡。移植后采用沙利度胺维持,随访3-12个月,病情稳定。结论:PAD用于难治MM患者的治疗达CR后,继续序贯进行APBSCT不仅可行,而且PAD不影响正常造血干细胞动员,故采用PAD和序贯用PAD+CTX动员方案的APBSCT的治疗手段,为难治MM患者的治疗提供新的治疗手段。但对长期生存的改善作用需进一步研究。     

来那度胺联合抗B细胞成熟抗原嵌合抗原受体T细胞治疗复发难治多发性骨髓瘤一例并文献复习

目的:探讨来那度胺联合抗B细胞成熟抗原（BCMA）嵌合抗原受体T细胞（CAR-T）治疗复发难治多发性骨髓瘤（RRMM）的临床效果。方法:回顾分析河南省中医院2020年1月收治的1例接受来那度胺联合抗BCMA CAR-T治疗的RRMM患者临床资料,分析其临床特点及诊治情况,并复习相关文献。结果:患者为51岁男性,2015年10月确诊IgD-λ型多发性骨髓瘤（MM）,接受包括免疫调节剂和蛋白酶体抑制剂等方案化疗10个疗程后缓解,随后接受自体造血干细胞移植;移植后14个月MM复发,采用多种化疗方案及鼠源和人源抗BCMA CAR-T治疗,病情持续进展。用氟达拉滨和环磷酰胺预处理后,-1天服用来那度胺,次日输注人源抗BCMA CAR-T,输注后发生3级细胞因子释放综合征（CRS）,对症治疗后缓解。抗BCMA CAR-T治疗后14 d原发病评估达非常好的部分缓解（VGPR）,至截稿前已维持VGPR 3个多月。结论:来那度胺联合抗BCMA CAR-T治疗RRMM是可行的和有效的。     

Strategien beim rezidivierten/refraktären multiplen Myelom

Context

Multiple myeloma is a malignant lymphoproliferative B-cell disease of the bone marrow characterized by proliferation of monoclonal plasma cells. Approximately 95?% of patients develop recurrent disease.

Objective

A structured review of the treatment options for relapsed multiple myeloma is summarized using current publications.

Results

Novel agents, such as thalidomide, bortezomib and lenalidomide have improved the outcome in patients with recurrent/relapsed myeloma and resulted in prolongation of overall survival. High-dose therapy followed by autologous hematopoietic stem cell transplantation (ASCT) should be considered as a treatment option for patients in a good general condition and with a prolonged disease control (at least 12–24 months) after upfront ASCT.

Conclusion

Treatment strategies for myeloma patients depend on the general physical condition and response as well as side effects of previous therapies. Carfilzomib and pomalidomide should be considered as new treatment options for patients with recurrent/relapsed myeloma refractory to bortezomib and/or lenalidomide. Further drugs are currently being evaluated in several clinical trials. Allogeneic haematopoetic stem cell transplantation is still debateable and should only be considered as a treatment option within clinical trials.