多发性骨髓瘤的治疗现状和规范

多发性骨髓瘤(MM)是一种异常浆细胞过度增殖的恶性肿瘤,传统化疗效果不佳,完全缓解率(CR)＜10％,中位生存期仍然只有33个月左右.自体造血干细胞移植(ASCT)的应用改善了MM的疗效,含新药的诱导化疗能达到与移植相似的疗效.目前认为,含新药的诱导治疗序贯ASCT是≤65岁适合移植的初治MM患者的治疗策略,单次移植后疗效≥非常好的部分缓解的患者不需要二次移植.移植后的巩固和维持治疗是有益的.对于＞65岁及不适合移植的初治MM患者,含新药的诱导治疗和维持治疗同样是合适的.     

自体造血干细胞移植是适合移植的多发性骨髓瘤患者的标准治疗?

自体造血干细胞移植(autologous stem cell transplantation, ASCT)是多发性骨髓瘤的标准治疗策略之一。不论是传统药物时代, 还是新药时代, ASCT均作为多发性骨髓瘤治疗的重要手段之一。尽管文献报道ASCT可延长患者的无进展生存期, 但对总生存期的获益有待进一步探讨, 特别是高危患者, ASCT可能并不能使患者获益。此外, ASCT后的巩固、维持治疗对预后也至关重要, 且ASCT具有存在相关不良反应以及再发肿瘤的风险, 故ASCT用于多发性骨髓瘤治疗的价值仍有待商榷。     

自体造血干细胞移植与新药化疗治疗新诊断多发性骨髓瘤的倾向性评分匹配研究

目的:比较新药时代自体造血干细胞移植(ASCT)和新药化疗治疗新诊断多发性骨髓瘤(NDMM)的临床疗效、生存期及预后分析。方法:回顾性分析2012年1月至2019年12月华中科技大学同济医学院附属协和医院采用新药方案诱导化疗的149例NDMM患者的临床资料,24例接受ASCT的患者为移植组,125例未接受ASCT的患者为非移植组,中位随访时间43(1-90)个月。采用倾向性评分匹配法均衡组间混杂因素后比较组间缓解深度、总生存时间(OS)、无进展生存时间(PFS),并进行亚组分析。结果:通过匹配组间的协变量达到均衡,51例患者进入研究,移植组15例,非移植组36例。匹配后,移植组完全缓解(CR)率较非移植组接受维持治疗的CR率高(93.3%vs 42.3%,P=0.004),而深度缓解率和总有效率差异均无统计学意义(93.3%vs 65.4%,P=0.103;93.3%vs 96.2%,P=1.000)。匹配前,移植组较非移植组3、5年的PFS率和中位无进展生存时间(m PFS)分别为(89.6%vs 66.5%,P=0.024;69.8%vs 42.7%;未达到vs 51.0个月),3...     

多发性骨髓瘤治疗现状及前景

多发性骨髓瘤(MM)是血液系统发病率第二的肿瘤。过去10年里,包含沙利度胺、硼替佐米、雷利度胺等药物新的联合化疗方案的应用,使得 MM 患者的缓解率、无进展生存期(PFS)及总生存期(OS)较长春新碱+阿霉素+地塞米松(VAD)、马法兰+泼尼松(MP)传统方案明显提高。自体造血干细胞移植(ASCT)技术的成熟、肿瘤抗原疫苗及细胞过继免疫等免疫治疗的应用,进一步降低患者复发率,明显改善预后。关于去乙酰化酶抑制剂等新型药物的探索及研究也取得突破性进展,显现出现良好的前景。现就近年来在 MM 的治疗中取得的进展综述如下。     

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.     

56例多发性骨髓瘤行患者自体造血干细胞移植治疗的临床疗效分析

目的:评估自体造血干细胞移植(auto-HSCT)治疗多发性骨髓瘤(MM)的疗效及对预后生存的影响。方法:回顾性分析自2008年12月至2016年9月在天津市肿瘤医院血液科诊断并接受auto-HSCT治疗的56例MM患者的临床资料。结果:所有患者移植后造血均顺利重建,无移植相关死亡。56例患者在诱导治疗后和auto-HSCT后的完全缓解(CR)率分别为23.2%(13/56)和78.6%(44/56)(P 0.01)。诱导治疗后和auto-HSCT后的CR+VGPR率分别为53.6%(30/56)和94.6%(53/56)(P 0.01)。中位无进展生存期(PFS)为37个月,中位总生存期(OS)为71个月。采用含硼替佐米方案诱导化疗的患者中位PFS时间为37个月,中位OS时间未达到;而采用未含硼替佐米方案诱导化疗的患者中位PFS时间为27个月(P 0.01),中位OS时间为51个月(P0.01)。相关预后因素分析发现,auto-HSCT后CR+VGPR患者及诱导化疗周期数小于6次的患者与PFS密切相关(P 0.01)。结论:auto-HSCT可以进一步提高患者的CR率,延长PFS和OS时间。含硼替佐米化疗方案诱导后序贯移植是适合移植的MM患者的首选治疗方案。维持治疗使持续CR+VGPR的患者明显获益。     

沙利度胺在多发性骨髓瘤维持治疗中的Meta分析

目的综合评价沙利度胺(Thal)对多发性骨髓瘤(MM)患者维持治疗的预后和安全性影响。方法系统检索Pubmed、EMbase、Cochrane Library、中国生物医学文献数据库(CBM)、CNKI、维普和万方数据库截至2016年6月发表的关于Thal在MM维持治疗的随机对照研究(RCT),采用Rev Man 5.2软件行Meta分析。结果最终纳入11个RCT,共4 694例患者。Meta分析结果显示,在MM患者维持治疗中,含Thal与不含Thal组无进展生存期(PFS)差异有统计学意义(HR=0.66,95%CI:0.61~0.72,P<0.000 01),但在总生存期(OS)方面无统计学差异(HR=0.95,95%CI:0.86~1.05,P=0.33)。亚组分析显示无论是否进行自体造血干细胞移植(ASCT),含Thal组均可延长PFS而不能使MM患者在OS方面获益。在安全性方面,含Thal组的血栓栓塞、乏力、神经病变、水肿、便秘的发生率显著增加(P均<0.05)。而高血糖、疼痛、肺炎、失眠、感染的发生率相当,差异无统计学意义(P均>0.05)。结论在MM维持治疗中,无论是否行ASCT,Thal能明显延长患者PFS,但增加了血栓栓塞、乏力、神经病变、水肿、便秘不良反应的发生率。     

适合造血干细胞移植多发性骨髓瘤患者的治疗

多发性骨髓瘤(multiple myeloma,MM)是浆细胞来源的恶性克隆性疾病,难于治愈。虽然近年来新药的出现明显改善MM患者的疗效,但研究证实适合于造血干细胞移植的患者仍需进行移植以进一步提高患者的治疗反应,延长生存期。本文就适合于造血干细胞移植的患者,如何根据患者情况制定个体化的整体治疗策略进行综述,重点阐述移植前合适的诱导治疗方案的选择、最佳移植时机的确定、造血干细胞移植方式的抉择和移植后合理的维持治疗。     

异基因骨髓移植治疗多发性骨髓瘤

异基因骨髓移植(alloBMT)仍是唯一有可能治愈多发性骨髓瘤(MM)的手段。新近研究显示,allo BMT可使MM患者长期生存率达4Q％,且大多数患者无残留病的证据。尽管骨髓抑制和移植物抗宿主病(GVHD)的发生率和死亡率相对较高,对于高危MM患者仍应在治疗的早期考虑alloBMT。 尽管标准化疗方案如马法兰和强的松对MM有效,但完全缓解(CR)者罕见,所有病人最终因疾病进展而死亡。更强的化疗方案并不延长患者的中数生存期(3年),却招致更快更重的细胞减少。强烈化疗、放疗后进行自体和异体造血干细胞移植显示alloBMT仍是有可能治愈MM的手段。     

抗体类新药治疗复发/难治性弥漫大B细胞淋巴瘤的研究进展北大核心CSCD

2019年我国新增霍奇金淋巴瘤(HL)9468例,新增非霍奇金淋巴瘤(NHL)91954例。HL的发病率和死亡率分别为0.57/10万和0.15/10万,而NHL的发病率和死亡率更是达到4.99/10万和2.32/10万[1]。弥漫大B细胞淋巴瘤(DLBCL)是最常见的淋巴瘤亚型,占所有淋巴瘤的35.8%[2]。随着规范化治疗的推广和新药的不断研发,DLBCL患者的生存获得了很大的改善。中国DLBCL患者的5年总生存(OS)率达到38.4%[3],其中一线接受利妥昔单抗联合含蒽环类药物化疗方案患者5年、10年OS率分别为69%、55.6%,接近欧美国家水平[4]。约60%的DLBCL初治患者可通过R-CHOP免疫化疗方案治愈。然而复发/难治性DLBCL(R/R DLBCL)患者接受现有的挽救化疗方案联合自体造血干细胞移植(ASCT)巩固治疗仅有10%的治愈率[5],不适合行ASCT或ASCT后复发患者的预后更差,中位生存期仅6~12个月左右[6-7]。近年来,虽然嵌合抗原受体T(CAR-T)细胞治疗的出现使部分R/R DLBCL患者获得持久缓解与长期生存,但是CAR-T细胞治疗高昂的费用、较长的制备周期、特殊的不良反应等诸多因素限制了其在临床的应用。抗体药物偶联物(ADC)、单克隆抗体和双特异性抗体等抗体类新药的研发与应用为R/R DLBCL的治疗打开了新局面。本文对这些抗体类新药或治疗方案在R/R DLBCL治疗领域的临床研究进展进行归纳和总结。     

The effect of comorbidity on survival and collected CD34 + cell counts in autologous hematopoietic stem cell transplant patients

ObjectiveIn this study, we aimed to report the effectiveness of hematopoietic cell transplantation–specific comorbidity index (HCT-CI) and GATMO scores in predicting overall survival (OS) who underwent autologous stem cell transplantation (ASCT).Material and methodsThe data of 263 MM and 204 lymphoma patients who underwent ASCT in the last 11 years were retrospectively analyzed.ResultsNeutrophil engraftment time, thrombocyte engraftment time and collected CD34+ cell counts were similar in MM patients with HCT-CI>2 and HCT-CI≤2 (all p>0.05). Although the estimated median OS of MM patients with HCT-CI ≤2 tended to be higher than those with HCT-CI>2, this difference was not statistically significant (52.8 vs 45 months, p=0.172). No effect of GATMO score on CD34 + count, engraftment times and OS in MM patients was detected (p>0.05). The effect of HCT-CI score on lymphoma patients was examined, it was found that the neutrophil engraftment time was longer (p=0.039) and the number of collected CD34+ cells was lower (p=0.02) in patients with HCT-CI>2 than those with HCT-CI≤2. While the estimated median OS of lymphoma patients with HCT-CI≤2 was 51.5 months, the estimated median OS of patients with HCT-CI>2 was 9.5 months (p=0.012). When lymphoma patients were divided into four groups according to their GATMO scores, the OS of the four groups was found to be different from each other (p<0.001).ConclusionHCT-CI and GATMO scores predict OS in lymphoma patients but not MM patients.     

Inferior prognosis in poor mobilizing myeloma patients

IntroductionInduction treatment followed by autologous stem cell transplantation (ASCT) has been accepted as the standard treatment for multiple myeloma (MM) patients. Granulocyte colony stimulating agent (G-CSF), chemotherapy or agents likes plerixafor are being used for the mobilization of stem cells from bone marrow. In this study, we evaluated the impact of the mobilization methods on the outcome of MM patients after ASCT.MethodThe data of 205 MM patients who underwent ASCT at our center between December 2009 and January 2019 were retrospectively analyzed. Patients were divided into 2 groups as good mobilizers (patients who were mobilized with G-CSF alone) and poor mobilizers (patients who were failed to mobilize with G-CSF alone and mobilized with G-CSF + cylophosphomide or G-CSF + plerixafor).ResultsThe median progression free survival (PFS) was 18.27 ± 3.22 months in good mobilizers and 14.22 ± 3.7 months in poor mobilizers. In G-CSF + cyclophosphamide method median PFS was 15.4 ± 4.9 months wheras it was only 4 months in G-CSF + plerixafor method. We did not find a statistically significant difference between good and poor mobilizers regarding median PFS (p: 0.342). The median overall survival (OS) was found 34.48 ± 4.2 months in good mobilizers and 15.13 ± 5.78 months in poor mobilizers. In G-CSF + cyclophosphamide method median OS was 17 ± 14.01 months wheras it was 10.66 ± 7.68 months in G-CSF + plerixafor method. We found a statistically significant difference between good and poor mobilizers regarding median OS (p: 0.007*).ConclusionOur study shows that difficulty in stem cell mobilization is correlated with worse outcome.     

造血干细胞移植治疗多发性骨髓瘤的研究

在常规化疗无明显改善多发性骨髓瘤(MM)无病生存率和总的生存率的情况下，造血干细胞移植在近十多年来广泛应用于MM治疗。自体外周血干细胞移植曾广泛用于MM治疗，可提高患者的缓解率，并延长生存期，但复发率高影响了其疗效。二次移植可再次提高患者的缓解率，但需进一步评价。异基因干细胞移植存在移植物抗骨髓瘤效应，可使1／3的患者达到分子学缓解，但移植相关死亡率高限制了其应用。正在临床广泛研究的非清髓性干细胞移植的移植相关死亡率低，存在移植物抗骨髓瘤效应，这可弥补以上不足。     

成人急性淋巴细胞白血病缓解后化疗和自体造血干细胞移植疗效的比较

目的比较联合化疗和自体造血干细胞移植（ASCT）在成人急性淋巴细胞白血病（ALL）缓解后治疗的疗效．方法对我院移植中心1990年7月至2003年12月首次诱导缓解、早期连续强化巩固治疗4个疗程后接受ASCT或联合化疗的74例成人ALL患者的疗效进行回顾性分析。联合化疗患者40例，ASCT患者34例，中位随访时间20．5个月，比较两组患者累积无白血病生存（LFS）率、总生存（OS）率及累积复发率：结果①化疗组患者中位LFS和OS期分别是14．0和20．6个月，而ASCT组中位LFS和OS期均大于53．5个月；②化疗组患者28例（70％）复发，而ASCT组患者移植后11例（32．35％）复发；③ASCT组患者1年LFS、OS率及复发率与化疗组患者相比差异无统计学意义（P值均〉0．05），而3年及5年预期LFS和OS率明显高于化疗组（P值均〈0．05），ASCT组患者的3年及5年复发率显著低于化疗组（P〈0．05）；④ASCT前移植物体外净化和移植后维持治疗（处理组）患者3年以上LFS和OS率高于未处理组患者（P〈0．05），累积复发率低于未处理组患者（P〈0．05）。结论ASCT可以有效降低成人ALL患者在早期连续强化巩固治疗后的远期复发率；ASCT前体外净化和移植后维持治疗可降低复发率，提高长期生存率。     

Ustekinumab: targeting the IL-17 pathway to improve outcomes in psoriatic arthritis

ABSTRACT

Introduction: Autologous Stem Cell Transplantation (ASCT) represents the standard treatment in eligible “de-novo” multiple myeloma (MM) patients.

Areas covered: ASCT may be single or tandem, and a single ASCT can be followed by an allogeneic (Allo)-SCT. A systematic review has been conducted to examine the current evidence for the efficacy of using a tandem transplant strategy in MM.

Expert opinion: A tandem ASCT approach should be considered for all patients, although the benefit from the second ASCT in patients who are in complete remission or experience a very good partial response should be answered in a clinical trial. Recent results with the new induction regimens indicate that there is a role for tandem ASCT in the presence of adverse cytogenetic abnormalities. Planned AlloSCT after ASCT has not been found to be superior in the majority of studies and is not recommended outside of a clinical trial. However, single or tandem ASCT are both appropriate options and participation in prospective clinical trials should be encouraged to resolve the debate in the era of novel agents for MM.     

Bone marrow transplant for multiple myeloma: impact of distance from the transplant center

Purpose: This study investigated the impact of prognostic variables, including the distance a patient lives from a transplant center, on the outcome of autologous hematopoietic stem cell transplantation (ASCT) for multiple myeloma. Methods: This retrospective analysis included 77 myeloma patients who received an ASCT at Dartmouth Hitchcock Medical Center between 1996 and 2009, 70 of whom were treated between 2002 and 2009. Using linear regression and univariate analysis, we examined the impact of distance from the transplant center on survival. Kaplan-Meier curves identified overall and event-free survival. An association between distance from the transplant center and survival was examined using Cox regression analysis, while adjusting for patient-, disease-, and treatment-related variables. Results: Increasing distance from the transplant center correlated with improved overall survival (P=.004), but had no impact on disease-free survival (P=.26). Conclusions: These results suggest that the distance from a transplant center should not be a barrier to ASCT for eligible patients with multiple myeloma.     

Treatment Outcomes and Health Care Resource Utilization in Patients With Newly Diagnosed Multiple Myeloma Receiving Lenalidomide-only Maintenance,Any Maintenance,or No Maintenance: Results from the Connect MM Registry

Purpose

Maintenance therapy after autologous stem cell transplantation (ASCT) improves clinical outcomes in multiple myeloma (MM), but the effect of continued treatment with lenalidomide-only maintenance, or any maintenance, on health care resource utilization (HCRU) is largely unknown.

Does ferritin level affect the outcomes of autologous stem cell transplantation equally in all diseases?

BackgroundIn this retrospective study, we evaluated the effect of ferritin levels on the outcomes of autologous stem cell transplantation in patients with MM or lymphoma.MethodsIn this study, 170 patients with measured ferritin levels within one month before transplantation who underwent ASCT with the diagnosis of MM or lymphoma were evaluated. The cut-off value of ferritin was determined as 500 ng/mL to evaluate the transplant outcomes in both groups. The hematological recovery status/duration, febrile neutropenia rate, hospitalization time, transplant-related mortality (TRM) in the first 100 days, and OS were evaluated according to the ferritin levelResultsOf all patients, 105 (61,8%) were diagnosed with MM and 65 (38.2%) with lymphoma. Ferritin levels had no statistically significant effect on the engraftment status/times, the febrile neutropenia rates, and hospitalization times of both lymphoma and myeloma patients (p > .05). Ferritin level was not significantly associated with TRM in MM (p = .224). However, in lymphoma, ferritin level was significantly associated with TRM (33.3% for ferritin level ≥500 ng/L vs. 5.3% for ferritin level ng/mL, p = .005). There was no statistically significant correlation between ferritin value and OS in MM group [ferritin level ≥ 500 ng/L: 39.9 months (95% CI: 33.7–46.1) and ferritin level 500 ng/mL: 39.4 months (95% CI: 36.5–42.2), p = .446]. Ferritin level was significantly associated with OS in patients with lymphoma [ferritin level ≥ 500 ng/L: 22.1 months 95% CI: 14.7–29.5), ferritin level 500 ng/mL: 27.3 months (95% CI: 22.4–32.2), p = .038]ConclusionHigh ferritin level is important prognostic factor on survival after ASCT in patients with lymphoma.