非清髓性造血干细胞移植治疗老年恶性肿瘤

老年恶性肿瘤患者常无法耐受传统大剂量放化疗预处理，非清髓性造血干细胞移植(NST)以免疫抑制为主，降低了放化疗强度，为不适合做传统移植的患者带来希望。     

非清髓性异基因造血干细胞移植治疗恶性肿瘤

非清髓性异基因造血干细胞移植 ,主要是通过移植物抗肿瘤效应来根除恶性肿瘤细胞 ,与经典的清髓性异基因造血干细胞移植相比 ,其移植相关并发症和病死率降低 ,对年龄较大、体质差的患者是一种较为安全可靠的治疗手段     

非清髓性异基因造血干细胞移植治疗恶性肿瘤

非清髓性异基因造血干细胞移植,主要是通过移植物抗肿瘤效应来根除恶性肿瘤细胞,与经典的清髓性异基因造血干细胞移植相比,其移植相关并发症和病死率降低,对年龄较大、体质差的患者是一种较为安全可靠的治疗手段.     

非清髓性异基因造血干细胞移植治疗多发性骨髓瘤一例

患者男 ,4 2岁。因反复腰痛 8个月 ,于 2 0 0 0年 5月 2 4日入院。经骨髓、Ｘ线、血清Ｍ蛋白等检查 ,诊断为多发性骨髓瘤ⅢＡ期。用ＶＢＡＰ方案 (ＶＣＲ、ＢＣＮＵ、ＡＤＲ、Ｐｒｅｄ)化疗 1个疗程 ,骨髓象浆细胞由 2 2 .5 %上升到 39%。随后改用大剂量环磷酰胺 (ＣＴＸ)治疗 ,共 2个疗程 ,骨髓象浆细胞降至3.5 % ,血浆Ｍ蛋白由 35 .8%降至 2 5 .8%。随后即以非清髓性预处理策略行异基因外周血造血干细胞移植 (ａｌｌｏ ＰＢ ＳＣＴ)。供者为其胞姐 ,ＨＬＡ配型全相合 ,ＡＢＯ血型供者为Ｏ型 ,受者为Ｂ型 ,属次要不合 ,供者每天用ｒｈＧ Ｓ…     

非清髓性同种造血干细胞移植治疗恶性实体瘤13例

目的:探讨非清髓性同种外周血造血干细胞移植治疗复发及难治性实体瘤的疗效及安全性,并研究移植物抗肿瘤效应(GVT)产生的抗肿瘤免疫效果.方法:13例患者.其中原发不明癌5例,其他经手术,放、化疗治疗后复发及多部位转移,难治性实体瘤8例.年龄17～69岁,中位年龄45岁.ECOG分级:0级5例,1级6例,2、3级各1例.全部患者给予非清髓性预处理方案进行同种外周血造血干细胞移植.供者为HLA完全相合者10例,非血缘关系者3例.ABO血型相合9例,不相合者4例.采集CD34~+数为1.4～6.6×10~4/kg,平均为3.46×10~6/kg.预处理方案三种:供者为同胞的患者采用环磷酰胺+氟达拉宾方案;非血缘供者患者采用氟达拉宾+马法兰方案.移植物抗宿主病(GVHD)防治采用环孢素A或加用甲氨蝶呤.疗效判定以治疗前后肿瘤大小做为移植物抗肿瘤(GVT)效果判定.同时观察同种造血干细胞移植的副作用.结果:全部患者均获造血重建,移植后中性粒细胞>0.5×10~9/L平均时间11.9天,血小板>20×10~9/L平均时间14.9天,不良反应主要表现为胃肠道、皮肤黏膜及神经系统.急性GVHD9例,经治疗后好转.慢性GVHD8例,均为广泛型.GVT效应:1例GVT+++,肿瘤完全消失,无瘤生存887天.3例GVT++,无瘤生存334天.5例GVT+,无瘤生存117～203天.移植效果:以持续3个月以上统计,CRI例,PR2例,SD4例,PD5例,移植相关死亡1例.总有效率为53.8%.不良反应:主要为急性GVHD,表现为胃肠道反应如腹泻,感染等,肝静脉血栓及脑病少见,经对症治疗好转.结论:对复发及难治性实体瘤,特别是原发不明癌采用非清髓性同种外周血造血干细胞移植可提高疗效,并通过移植物抗肿瘤效应使瘤体减小,延长患者生存期.本疗法具有较好的安全性.     

非清髓异基因外周造血干细胞移植治疗难治性恶性血液病

目的:观察非清髓异基因外周造血干细胞移植(NAST)对难治性恶性血液病的疗效。方法:采用NAST治疗 3例慢性粒细胞白血病加速期(CML -AP)、1例骨髓增生异常综合征(MDS-RAEB T)患者。非清髓预处理方案:氟达拉宾 (Flud)30mg·m-2·d-1×6d,白消安(Bu)4mg·kg-1·d-1×2d,环磷酰胺(CTX)600mg·d-1×2d,3例CML- AP患者在此基 础上加用阿糖胞苷(Ara c)。结果:4例患者造血均顺利恢复,ANC>0.5×109/L平均为12天,BPC>20×109/L平均为11天。 +30天时经短串联重复序列(STR)- PCR检测3例患者为完全嵌合体(CC),1例慢粒患者为混合嵌合体(MC),+90天时全部 患者均处于CC。分别随访4月～16月,均无病存活。结论:非清髓异基因外周造血干细胞移植是治疗CML- AP、MDS -RAEB T 等难治性恶性血液病的有效手段。     

非清髓性异基因造血干细胞移植的创新与展望

非清髓性异基因造血干细胞移植(NST)是在传统异基因造血干细胞移植的基础上发展起来的新移植领域,它减轻了预处理强度并加强了移植前后的免疫处理.因其并发症轻、危险性小而有广泛的应用前景,也有许多未知领域有待继续探讨.     

非清髓异基因外周造血干细胞移植治疗老年重型再障报告

目的 :探讨非清髓异基因外周造血干细胞移植 (NAST)治疗老年重型再生障碍性贫血 (SAA)的方法及疗效。方法 :采用非清髓预处理的异基因外周造血干细胞移植治疗老年 SAA患者1例。供受者 HL A配型及红细胞 ABO血型完全相合。预处理方案主要由环胞霉素 A(Cs A)、抗淋巴细胞球蛋白 (ATG)和环磷酰胺组成。用环胞霉素 A和霉酚双酯 (MMF)预防移植物抗宿主病(GVHD)。采用 STR- PCR定量方法检测供者细胞植入情况。结果 :该例老年 SAA患者顺利度过移植后造血抑制期 ,于移植后第 8天外周血 WBC升至 0 .8× 10 9/ L,第 14天血象三系恢复 ,于移植后第 14天、30天、90天及 180天时检测供者细胞植入率均为完全植入。患者未出现移植物抗宿主病 ,现己无病存活 31个月。结论 :非清髓异基因外周造血干细胞移植简便安全 ,并发症少 ,疗效好 ,为老年 SAA的治疗提供了新手段     

重视非清髓性异基因造血干细胞移植治疗白血病的研究

近年来,白血病化疗的进展不断深入,但临床疗效的提高尚不显著.大组病例观察证实,初诊急性非淋巴细胞白血病(ANLL)(除外急性早幼粒细胞性白血病,M3)及成人急性淋巴细胞白血病(ALL)的缓解率基本保持在55%～70%和68%～80%左右.     

非清髓性异基因造血干细胞移植研究进展

1 异基因外周血造血干细胞移植概况 异基因外周血造血干细胞移植（allogeneic peropheral biood stem cell trans[lantation allo-PBSCT)是目前治疗血液病     

Second solid cancers after allogeneic hematopoietic stem cell transplantation

BACKGROUND: The objective of this study was to establish the incidence and risk factors for the development of second solid cancers after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The authors reviewed the case files of 926 consecutive patients who underwent allo-HSCT at their institution between 1985 and 2003. RESULTS: Twenty-eight patients developed 30 solid malignancies at a median of 6.8 years after allo-HSCT (range, 0.12-17.3 years) for a 10-year cumulative incidence of 3.1% (95% confidence interval [95% CI], 2-5%; all solid tumors) and 2.3% (95% CI 1-4%; excluding basal cell carcinoma and carcinoma in situ). The risk ratio of developing a second solid malignancy after allografting, compared with the general population of British Columbia adjusted for age and sex, was 1.85 (95% CI, 1.04-3.06; P = .019). In multivariate analysis, recipient age at allo-HSCT >40 years (P = .005) and having a woman donor (P = .0008) were associated with a greater risk of developing a second solid cancer. CONCLUSIONS: The authors concluded that patients undergoing allografting are at increased risk of developing a second solid cancer compared with the general population, particularly those of advanced age at the time of allograft. It is noteworthy that patients who had women as graft donors had an increased risk for developing a second solid cancer. This unexpected finding is a new observation and has not been reported previously. Extended follow-up will be needed to assess more fully the incidence and risk factors for the development of solid cancers, because the latency can be prolonged.     

造血干细胞移植治疗实体瘤研究进展

目前实体瘤的治疗以放化疗为主,传统放化疗因存在耐药和不良反应而有一定局限性.造血干细胞移植支持下的大剂量放化疗可以减少耐药及不良反应,提高疗效,但目前仍存在移植后复发率高、生存期短的问题,如何加强后续治疗值得进一步研究.综述造血 F细胞移植治疗实体瘤的可行性、治疗时机、疗效.     

Targets of tumor immunity after allogeneic hematopoietic stem cell transplantation

The effectiveness of allogeneic hematopoietic stem cell transplantation for hematologic malignancies results from the donor immunity to antigens expressed in leukemia cells in the recipient. Similar immune responses have now been identified in patients with renal cell cancer with tumor regression after allogeneic hematopoietic stem cell transplantation. Further studies to identify relevant antigens and mechanisms of resistance may improve the effectiveness of this approach in patients with solid tumors.     

Reduced-intensity allogeneic hematopoietic stem cell transplantation (mini-transplantation) for solid tumors

There are accumulating evidence of immunological therapeutic effect induced by reduced-intensity allogeneic hematopoietic stem cell transplantation (mini-transplantation) for solid malignancies. The reduced toxicity of a mild preconditioning regimen in mini-transplantation has facilitated its application to patients with various solid tumors. The so-called graft-versus-tumor (GVT) effect usually appears when graft-versus-host disease develops. Therefore, it is suggested that the fundamental mechanism of the GVT effect is a reaction by T-lymphocytes against various tumor-associated alloantigens of the tumor cells. Although mini-transplantation appears effective in some patients with renal cell carcinoma or breast cancer, it is still unclear whether the therapeutic mechanism could work on other solid tumors. Well-designed prospective clinical trials are warranted in order to determine the role of mini-transplant in the therapeutic strategy for solid tumors.     

Imatinib combined with myeloablative allogeneic hematopoietic stem cell transplantation for advanced phases of chronic myeloid leukemia

To evaluat the efficacy and safety of myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) combined with imatinib for advanced chronic myeloid leukemia (CML), 15 patients with accelerated phase (n = 6) or blast crisis (n = 9) were enrolled in this study. All the patients were conditioned with cyclophosphamide and busulfan, and treated with cyclosporin (CsA)/methotrexate (MTX)/mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis. Eleven of these 15 patients (73.3%) achieved complete hematologic response to pre-transplant imatinib, and six (40%) achieved a cytogenetic response. No engraftment failure was observed and the early transplant-related mortality was only 6.7%. Grade 3/4 acute GVHD occurred in 13.3% of patients. Chronic GVHD was observed in 61.5%, including 23.1% suffered from extensive disease. The 5-year estimated rates of relapse, transplant-related mortality and overall survival were 21.0 ± 10.8% 13.7 ± 10.8% and 66.0 ± 12.4%, respectively. Ten (66.7%) of 15 patients are alive with complete molecular remission, even after a median follow-up of 25 months after withdrawal of imatinib. In conclusion, even CML in advanced phases may have a satisfactory outcome after myeloablative allo-HSCT combined with imatinib, which may provide good remission prior to transplantation and reduce relapse risk, with low toxicity.     

Nonablative allogeneic hematopoietic stem cell transplantation

During the past few years there has been an explosion of knowledge in nonablative allogeneic stem cell transplantation. This approach to transplantation relies more on the creation of "immunologic space" for engraftment rather than the more traditional approach of creating "physical space" by the application of either intensive radiation or chemical therapy. Nonablative allogeneic stem cell transplantation holds the promise of allowing powerful alloimmune responses to eradicate disease processes while minimizing the initial treatment-related morbidity and mortality, and it appears to be the necessary enabling platform by which to apply allogeneic cellular therapy. Intuitively, this approach should broaden the eligibility for potentially curative allogeneic transplantation in various disease categories, reduce initial hospitalization costs, and at the same time have a positive impact on quality of life. We review the current published data relating to this approach including the underlying principles, the preparative regimen, disease indications, preliminary results in hematologic and solid malignancies, and certain correlative immunologic evaluations.     

异基因造血干细胞移植相关研究进展

近年来移植技术的不断改进使异基因造血干细胞移植(allo-HSCT)的适应证不断扩展,单倍型供者数量的增加使人类白细胞抗体阳性患者的处理备受关注,解决allo-HSCT患者的复发问题仍是国内外学者研究的热点.文章结合第59届美国血液学会(ASH)年会的报道,对allo-HSCT的相关研究进展进行综述.     

异基因造血干细胞移植相关研究进展

近年来,单倍体相合造血干细胞移植的发展使“人人都有移植供者”成为现实.因此,选择合适的供者以及解决移植相关并发症,如促进植入、降低移植后移植物抗宿主病的发生率和复发率成为改善移植预后的关键问题.文章介绍了异基因造血干细胞移植的相关研究进展.     

非清髓性异体外周造血干细胞移植治疗晚期实体肿瘤的研究进展

目的:总结非清髓性异体外周造血干细胞移植(Allo-PBSCT)治疗实体肿瘤的研究现状,探讨其治疗作用及关键技术。方法:应用Medline、PubMed全文数据库检索系统,以"异基因造血干细胞移植,限制剂量强度,移植物抗肿瘤效应,实体肿瘤"等为关键词,检索1995-2010年的相关文献,以非清髓性异体外周造血干细胞输注此项技术用于晚期实体肿瘤的临床治疗为纳入标准,分析文献30篇。结果:Allo-PBSCT可用于晚期难治性恶性肿瘤患者的治疗,它能够提高患者的生存时间和生活质量,是治疗晚期难治性恶性肿瘤的有效手段之一。但是,此项治疗技术亦存在问题,大多数晚期肿瘤患者体质弱,建立起适合我国晚期癌症患者的限制剂量强度的预处理方案尚需进一步探索;移植相关并发症导致患者死亡是限制此项技术临床应用的瓶颈。结论:Allo-PBSCT治疗晚期难治性恶性肿瘤的临床研究结果令人鼓舞,但是如何降低移植物抗宿主病(GVHD)效应的同时增强移植物抗肿瘤效应(GVT)效应是此项技术能否成功的关键,值得临床进一步深入研究。