自体造血干细胞移植可使中国高危多发性骨髓瘤患者获益更多

目的 评价自体造血干细胞移植（ASCT）对初治多发性骨髓瘤（MM）的疗效.方法 选取诱导治疗后获得部分缓解（PR）及以上疗效的42例初治MM患者进行ASCT,中位随访34.2个月后,观察患者的疗效、无进展生存（PFS）和总生存（OS）.选择同时期的49例诱导治疗后获得PR及以[上疗效的初治MM患者,进入非移植组（non-ASCT）,经巩固维持治疗后观察疗效、PFS和OS,比较两组的差异,分析ASCT在MM中的作用.结果 与non-ASCT组相比,ASCT可明显延长患者的OS（未达到/37.2个月,P=O.000）,而且对PFS也有延长趋势（33.9个月/39.8个月,P=0.133）.ASCT可明显改善DSⅢ期（P=0.009）和ISSⅢ期（P=0.049）患者PFS,但对DSⅠ /Ⅱ期和ISS Ⅰ/Ⅱ期患者的PFS改善不明显.ASCT可明显改善诱导治疗后获得CR患者的PFS（P=0.016）,对非常好的PR （VGPR） /PR患者的PFS改善不明显;不同年龄患者OS均明显改善（≤55岁,P=0.039;＞ 55岁,P=0.000）.ASCT可明显改善不同ISS分期患者的OS（Ⅰ/Ⅱ期,P=0.003;Ⅲ期,P=0.012）,对DSⅢ期患者的OS也有明显改善作用（P=0.000）,但对DSⅠ/Ⅱ期患者OS的作用不明显（P=0.446）.诱导治疗后获得CR和VGPR/PR的患者进行移植后,OS可进一步得到改善（CR,P=0.004; VGPR/PR,P=0.004）.结论 ASCT可明显改善初治MM患者的生存,使高龄和分期预后不良的MM患者获益更多.     

异基因干细胞移植治疗恶性淋巴瘤

恶性淋巴瘤是自体干细胞移植（ASCT）的主要适应证,而异基因移植（allo-SCT）的应用相对较少。allo—SCT的复发率（RR）较ASCT低,但移植相关死亡率（TRM）较高,二者的长期总体生存率（OS）无统计学差异。ASCT治疗霍奇金病疗效良好,因此仅在自体干细胞获取困难或严重损伤时考虑allo—SCT。而某些亚型的非霍奇金淋巴瘤ASCT疗效很差,allo-SCT可使部分患者获得长期无病生存,可以优先选择allo-SCT。此外,非清髓性预处理、去T细胞、供者淋巴细胞输注等技术的进展有望控制allo-SCT的TRM,并保留移植物抗淋巴瘤作用,改善患者生存。     

异基因造血干细胞移植治疗高危多发性骨髓瘤临床分析

目的探讨异基因造血干细胞移植(allo-HSCT)治疗高危多发性骨髓瘤(MM)的效果和预后影响因素。方法回顾性分析2003年4月至2017年3月海军军医大学附属长征医院44例确诊并行allo-HSCT的高危MM患者临床资料。分析患者总有效率、复发率、非复发相关死亡(NRM)率、移植物抗宿主病(GVHD)发生率等;采用Kaplan-Meier法分析患者移植后总生存(OS)、无进展生存(PFS);采用Cox比例风险模型对预后影响因素进行回归分析。结果 44例患者移植后有38例可评估疗效。中位随访时间111个月(0～216个月), 其中22例生存, 22例死亡, 21例复发。移植前完全缓解(CR)率29.5%(13/44), 非常好的部分缓解(VGPR)率45.5%(20/44), 部分缓解(PR)率22.7%(10/44), 疾病稳定(SD)率2.3%(1/44);移植后CR率71.1%(27/38), VGPR率13.2%(5/38), PR率13.2%(5/38), 疾病进展(PD)率2.6%(1/38)。5年OS率、PFS率分别为51.8%、47.8%, 10年OS率、PFS率分别为...     

自体造血干细胞移植治疗霍奇金淋巴瘤38例临床疗效及预后影响因素分析

目的 探讨自体造血干细胞移植（ASCT）治疗霍奇金淋巴瘤（HL）的临床疗效以及影响预后的因素。方法 回顾2007年10月至2021年10月于郑州大学附属肿瘤医院经ASCT治疗的HL38例患者资料,Kaplan-Meier和Cox方法分析移植后疗效以及预后影响因素。结果 38例移植患者均获得造血重建。全组患者移植前后CR率分别为55.3%和81.6%,5年PFS和OS分别为76.1%和79.0%。单因素分析显示B症状、IPS评分、移植前缓解状态、结外受累和预处理方案（均P<0.05）是影响HL患者ASCT预后的因素,多因素分析显示B症状（P<0.05）是影响5年PFS的独立危险因素。结论 ASCT治疗高危、复发难治HL患者的疗效显著,有B症状是影响移植预后的独立危险因素。     

30例自体外周造血干细胞移植治疗多发性骨髓瘤的疗效及预后因素评价

目的：对30例多发性骨髓瘤（multiple myeloma,MM）患者经自体外周造血干细胞移植（autologous hematopoietic stem cell transplantation ,APBSCT）治疗后的临床疗效进行评估,并分析可能影响预后的因素。方法：30例MM患者有2 例复发行2 次APBSCT,因此共计移植32例次。移植前予常规联合化疗（11例含万珂）,化疗联合G-CSF 动员APBSC ,选择以马法兰为基础的预处理方案,d0 天回输。结果：动员后患者采集的单个核细胞（MNC）中位数为6.41× 10⁸/kg,CD34+细胞4.75× 10⁶
/kg。APBSCT后中位中性粒细胞和血小板重建时间分别为9.5 天和11天。APBSCT后CR和VGPR 率分别为37.5% 和34.4% ,中位生存期（overallsurvival ,OS）为67.27个月,中位无进展生存期（progression-freesurvival ,PFS）为29.77个月,其中CR组、PR组中位PFS 分别为29个月、20个月,VGPR 组中位PFS 未达到,CR+VGPR组与PR组PFS 比较P=0.025。万珂组和非万珂组CR率分别为63.6% 和23.8%（P=0.034）,万珂组中位OS及PFS 均未达到,非万珂组中位PFS 为22个月（P=0.045）。 结论：硼替佐米诱导序贯APBSCT可获得更长的无病生存。APBSCT作为MM诱导缓解后的强化治疗,缓解率高,且移植后获得VGPR 以上反应的患者PFS 获益。     

新药诱导后自体干细胞移植巩固治疗对不同危险度骨髓瘤患者的作用探讨*

目的：探讨自体造血干细胞移植（autologous hematopoietic stem cell transplantation ,ASCT）作为新药诱导后的巩固治疗对不同危险分层骨髓瘤患者的无进展生存时间（progression-freesurvival ,PFS）及总生存时间（over all survival,OS）的影响。方法：回顾性分析2006年8 月至2011年7 月在本科行自体干细胞移植巩固治疗的67例多发性骨髓瘤患者,根据ISS 分期及FISH检测结果为基础的最新IMWG 预后标准分为高危组17例,中危组24例,低危组26例。另选取同时期67例接受化疗作为巩固治疗的骨髓瘤患者进行年龄、危险分层配对,比较移植组与化疗组的PFS 和OS差异。所有患者前期均接受硼替佐米和/或沙利度胺为主的诱导治疗。结果：所有患者诱导治疗后均达到部分缓解（partial remissive disease ,PR）以上疗效,移植组与化疗组vs . 接近完全缓解率（nCR/CR）差异无统计学意义（44.8% vs. 37.3% ,P=0.380）。 巩固治疗后,高、中、低危移植组患者中位nCR/CR率分别由47.1% ,37.5% ,50.0% 增加为62.9% ,62.5% ,61.5% 。高危患者移植巩固后中位PFS（30.5 个月vs. 11.2 月,P<0.001）和OS（85.5 vs. 34个月,P=0.015）均明显延长;中危移植组和化疗组中位PFS 和OS无统计学差异（P>0.05）;低危移植组患者与化疗组相比,中位PFS 延长（34.8 vs. 17.6 个月,P=0.012）,OS差异无统计学意义（P>0.05）。 结论：在硼替佐米和/或沙利度胺为基础的新药诱导治疗后,高危骨髓瘤患者更能从自体造血干细胞移植巩固治疗中获益,进而延长生存。     

成人急性淋巴细胞白血病自体造血干细胞移植后的维持治疗

目的 探讨成人急性淋巴细胞白血病(ALL)自体造血干细胞移植(ASCT)后维持治疗的可行性。方法 第1次完全缓解期(CRl)进行ASCT成人ALL患者38例,预处理方案为全身照射 环磷酰胺(TBICy)方案或者TBICy联合其他化疗药物,ASCT后19例患者接受VP／MM方案维持化疗,13例间断IL-2治疗,其中8例联合IL-2和维持化疗。结果 随访中位时间991(18～4914)d。复发11例,复发率28．9％,复发中位时间212(79～1008)d,其中8例在1年内复发。3年累积复发风险43．8％(95％可信限：35．1％～52．5％)。移植相关死亡(TRM)5例,TRM中位时间42(18～120)d,其中ASCT后接受维持治疗的24例患者仅2例发生TRM。3年和5年无白血病生存率均为55．7％(95％可信限：47．3％～64．1％)。结论 成人ALL患者ASCT后标准方案维持化疗和免疫治疗安全有效,能够减低移植后复发风险,提高ASCT的疗效。     

大剂量BEAC方案联合自体外周血干细胞移植治疗非霍奇金淋巴瘤临床分析

目的:观察BEAC方案作为预处理方案联合自体干细胞移植(autologous stem cell transplantation,ASCT)治疗非霍奇金淋巴瘤(non-Hodgkin’s lymphoma,NHL)的疗效。方法:选取2000-01-2011-12新疆医科大学附属肿瘤医院收治的NHL患者共45例,采用BEAC方案联合ASCT治疗,动员方案为依托泊苷(Vp-16)联合粒细胞集落刺激因子(G-CSF)。41例患者采用BEAC联合ASCT方案作为巩固治疗,4例采用BEAC联合ASCT方案作为挽救治疗。结果:45例患者均移植成功,重建造血功能。不良反应均可耐受,无移植相关死亡。移植前CR 53.3%(24/45),PR 46.7%(21/45),移植后CR 73.3%(33/45),PR 26.7%(11/45)。中位随访时间为41个月(8~139个月),至随访截止日期6例因疾病进展死亡,1例因第二原发肿瘤死亡。5年生存率为83.3%。结论:BEAC预处理方案联合ASCT方案治疗NHL安全性高,疗效较好。     

自体造血干细胞移植治疗多发性骨髓瘤

 自体造血干细胞移植（ASCT）治疗多发性骨髓瘤进展较大。与常规方案相比，ASCT提高了患者的完全缓解（CR）、无事件生存（EFS）和总生存率（OS）。高龄、肾衰竭并非ASCT的禁忌证。双次ASCT可提高CR率，对长期EFS率、OS率影响仍需观察。改进预处理方案、选择移植时机、改进移植后巩固治疗可以提高疗效。     

来那度胺治疗复发难治弥漫大B细胞淋巴瘤效果观察

目的探讨来那度胺联合二线免疫化疗作为挽救方案治疗复发难治弥漫大B细胞淋巴瘤(DLBCL)患者的临床疗效。方法回顾性分析中国科学技术大学附属第一医院2016年1月至2020年12月收治的37例自体造血干细胞移植后复发或不符合移植条件或无移植意愿、接受来那度胺联合二线免疫化疗方案治疗的复发难治DLBCL患者临床资料。其中6例为原发性中枢神经系统淋巴瘤, 3例为继发性中枢神经系统淋巴瘤。评估治疗结束后的近期疗效。采用Kaplan-Meier法分析患者总生存(OS)和无进展生存(PFS), 亚组间比较采用log-rank检验。结果 37例患者中位随访时间为20.4个月(2.7～37.0个月)。治疗结束时, 所有患者的总有效率(ORR)为64.9%(24/37), 完全缓解(CR)率为45.9% (17/37), 24例对治疗有反应患者的中位反应持续时间(DOR)为17.7个月(3.6～33.6个月)。所有患者的中位PFS时间为11.2个月, 1年PFS率为48.6%(95%CI 32.5%～64.7%)。所有患者的中位OS时间未达到, 1年OS率为67.6%(95%CI 52.5%～82.7%...     

Efficacy of up-front treatment with a double stem cell transplantation in multiple myeloma

BACKGROUND: We report the outcome of 53 patients with multiple myeloma (MM), who received autologous stem cell transplantation (ASCT) from April 1996 to September 2004 at our institution and who survived for more than 3 months after the transplant. METHODS: Following the first ASCT, 36 patients underwent an up-front second SCT, which consisted of either an ASCT (n = 24) or a reduced-intensity conditioning allogeneic stem cell transplant (RIST) (n = 12). Seventeen patients were given maintenance treatment. RESULTS: Seventy-seven percent of the patients (n = 41) showed an objective response to the initial therapy prior to the first ASCT. Overall, 60.4% (32 out of 53) and 32.1% (17 out of 53) of the patients had a complete response (CR) and partial response (PR) after the first ASCT, respectively. At the time of analysis, 34 patients (64.2%) were still alive. With a median follow-up of 32 months (range 9-98), the estimated progression-free survival (PFS) and overall survival (OS) at 5 years were 17.0 and 34.9%, respectively. Multivariate analysis revealed that the second SCT, normal hemoglobin and <50% marrow plasma cells were associated with an improved PFS. A second SCT, CR to the first SCT, female gender and an absence of advanced bone lesions were associated with a better OS. CONCLUSIONS: A second SCT is the most significant factor for an improved PFS and OS after the first ASCT (P < 0.001, respectively). Up-front double SCT is needed to improve the OS and PFS in patients with MM.     

Autologous stem cell transplantation for elderly patients with newly diagnosed multiple myeloma in the era of novel agents

BackgroundHigh-dose therapy (HDT) with autologous stem cell transplantation (ASCT) is considered the standard of care for multiple myeloma (MM) patients <65 years. Safety and outcome of ASCT for patients >65 years is currently uncertain, especially since the introduction of novel agents for induction and maintenance therapy. Furthermore, there are no conclusive data available on risk assessment in elderly patients treated with HDT.Patients and methodsWe retrospectively analyzed 202 patients ≥60 years with newly diagnosed MM who underwent ASCT at our institution. Patients were stratified by age into three groups (60–64, 65–69 and 70–75 years). For safety assessment, we compared data about hospitalization, hematopoetic reconstitution and early mortality. Remission before and after ASCT was analyzed according to age and application of novel agents. Event-free (EFS) and overall survival (OS) were analyzed to identify impact of age, remission before/after ASCT and maintenance therapy as well as ISS score and cytogenetic aberrations on outcome in elderly patients.ResultsThe assessment of safety, remission before/after ASCT as well as EFS and OS showed no significant differences between the three groups (median EFS: 60–64 years: 27 months; 65–69 years: 23 months; 70–75 years: 23 months; median OS: not reached). Patients receiving novel agents as part of induction therapy achieved significantly higher nCR + CR rates than patients treated without novel agents. In Cox regression analysis, ISS and cytogenetics as well as remission after ASCT had the highest prognostic impact on EFS and OS. Maintenance therapy was associated with longer EFS in uni- and multivariate analyses.ConclusionASCT is feasible for selected patients >65 and >70 years without increased mortality. Age at transplantation has no prognostic significance on outcome after ASCT. Novel agents during induction therapy and maintenance therapy improves outcome of older patients eligible for ASCT. ISS and cytogenetic analysis should be carried out routinely for risk assessment.     

新药时代造血干细胞移植治疗多发性骨髓瘤研究进展

造血干细胞移植(HSCT)已成为多发性骨髓瘤(MM)的一线治疗方案.早期进行自体造血干细胞移植(ASCT)已成为年轻初发MM患者的标准治疗方法.在新药时代,新型制剂在HSCT前及HSCT后的巩固维持治疗中可提高HSCT疗效.对于治疗复发难治性MM,新药对HSCT的地位构成挑战.文章将总结近期HSCT在新药时代的临床研究,旨在明确新药时代HSCT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疗效及预后影响因素分析

目的:探讨自体造血干细胞移植治疗多发性骨髓瘤（MM）的疗效和影响MM患者预后的因素。方法:回顾性分析我院2012年01月至2019年12月37例接受自体造血干细胞移植的MM患者的临床资料,中位随访时间为55（1～91）个月。对37例患者的反应深度、无进展生存时间（PFS）、总生存时间（OS）和影响预后的相关因素进行分析。结果:移植后3月内疗效达到完全缓解率和深度缓解率均优于移植前（P＜0.01,P＜0.05）,移植前后总有效率（ORR）比较无统计学意义（P＞0.05）。患者3年、5年OS率为97.0%、81.4%;3年、5年PFS率为62.7%、51.0%;中位PFS和OS均未获得。单因素分析结果表明移植后3月内疗效获得深度缓解较未获得患者无论是OS 还是PFS均较优 (P均＜0.01);诱导化疗后获得深度缓解可明显延长OS（P＜0.05）;DS分期Ⅰ-Ⅱ期、mSMART3.0危险分层标危患者相比DS分期Ⅲ期、高危患者PFS均有明显优势(P＜0.05)。Cox 多因素回归分析显示,移植后3月内疗效达深度缓解是PFS和OS的独立预后因素,mSMART3.0危险分层也是PFS的独立预后因素。结论:自体造血干细胞移植可以提高 MM 患者的反应深度。移植前后疗效、DS分期和mSMART3.0危险分层均可影响MM患者生存率。移植后3月内疗效达深度缓解是PFS 和OS的独立预后因素,mSMART3.0危险分层也是PFS的独立预后因素。     

Comparison between autologous and allogeneic stem cell transplantation as salvage therapy for multiple myeloma relapsing/progressing after autologous stem cell transplantation

Allogeneic stem cell transplantation (allo‐SCT) offers a clinical option to young patients with multiple myeloma (MM) relapsing/progressing after autologous SCT (ASCT); however, this claim remains debatable. Thus, in this retrospective study, we analyzed 526 patients with MM who underwent SCT for MM relapsing/progressing after the prior ASCT using the registry data of the Japan Society for Hematopoietic Cell Transplantation (2001‐2015) and compared overall survival (OS) between allo‐SCT (n = 192) and autologous stem cell retransplantation groups (ReASCT; n = 334) based on risk factor points. Significant adverse factors for OS in all patients were (1) male sex, (2) less than partial response to SCT, (3) performance status of 2 to 4, and (4) short duration from the prior ASCT. We scored factor 2 as 1 point, factor 3 as 2 points, and factor 4 as 0, 1, or 2 points for more than 30, 9 to 30, or less than 9 months, respectively. We categorized patients into three risk subgroups based on their total points (0, 1‐3, and 4‐5 points), indicating the usefulness of this scoring system for prognosis prediction and treatment selection. Subgroup comparison revealed OS after ReASCT to be higher than that after allo‐SCT in the intermediate‐risk subgroup comprising the largest population (28.2% vs 21.5%, P < .004). We observed no significant advantages of allo‐SCT over ReASCT in the low‐ and high‐risk subgroups. These findings suggest that ReASCT is more advantageous than allo‐SCT in many patients with MM relapsing/progressing after the prior ASCT. However, long‐term survival patients were noted only in the allo‐SCT group, and allo‐SCT could exhibit clinical efficacy, particularly in the low‐risk group. While further examination is warranted, allo‐SCT could be a potential tool for a specific population with MM relapsing/progressing after the prior ASCT.     

造血干细胞移植治疗多发性骨髓瘤

 自体造血干细胞移植（auto-HSCT）显著提高了65岁以下多发性骨髓瘤（MM）患者的疗效,早期进行auto-HSCT已成为年轻初发MM患者的标准治疗方法。美法仑200 mg／m2目前仍被认为是最佳的预处理方案。对于首次自体移植后未达到非常好的部分缓解（VGPR）及以上疗效的患者,推荐采用序贯双次auto-HSCT以进一步提高疗效。新的治疗MM药物在auto-HSCT前和预处理中的应用可提高自体干细胞移植（ASCT）疗效。异基因造血干细胞移植（allo-HSCT）虽然 完全缓解（CR）率较高,但因具有较高的移植相关毒性,患者的长期生存率并不比ASCT高。减低剂量的allo-HSCT由于预处理毒性小,移植相关死亡率低,将可能成为一种安全有效的治疗方法。ASCT结合非清髓的allo-HSCT的疗效目前还需大样本的研究来证实。     

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.     

Autologous Stem Cell Transplantation for Multiple Myeloma: Identification of Prognostic Factors

IntroductionThe purpose of this study was to evaluate the effect of prognostic factors on the outcome of patients with MM after ASCT.Patients and MethodsWe analyzed results of 170 consecutive patients (121 male and 49 female) of MM who underwent ASCT. Patients' median age was 52 years (range, 26-68 years). High dose melphalan (200 mg/m²) was used for conditioning. One hundred thirty-two patients (77.6%) had evidence of chemosensitive disease before transplant. Response was assessed using European Group for Blood and Bone Marrow Transplantation criteria.ResultsPost ASCT 44.7% of patients achieved CR, 24.7% had very good partial response (VGPR), and 21.2% had partial response (PR). Presence of pretransplant chemosensitive disease (CR, VGPR, and PR) and transplant within 12 months of diagnosis for years before 2006 were associated with higher response rates on multivariate analysis. At a median follow-up of 84 months, median overall (OS) and event-free survival (EFS) is 85.5 and 41 months, respectively. Estimated OS and EFS at 60 months is 62 ± 0.04% and 41 ± 0.04%, respectively. Patients who responded to transplant (CR, VGPR, and PR) had a longer OS (P < .001) and EFS (P < .001). Additionally, patients who achieved CR post transplant had a longer OS (P < .001) and EFS (P < .001). Patients who received novel agents for induction pretransplant had a longer OS (P < .001) and EFS (P < .002).ConclusionOutcome after ASCT is better for myeloma patients with pretransplant chemosensitive disease and those who achieve CR after transplant.     

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。