非清髓性异基因造血干细胞移植在实体瘤治疗中的应用

异基因干细胞移植用于实体瘤的治疗有很大的潜力。传统的清髓性造血干细胞移植采用大剂量化疗药物对受者进行预处理,虽然起到一定的杀伤肿瘤细胞作用,但增加了移植相关死亡率（transplant-related mortality,TRM）。随着对非清髓性预处理的深入研究,人们将非清髓性造血干细胞移植用于实体瘤的治疗。与清髓性干细胞移植比较,非清髓性移植减轻了TRM,且拓宽了移植适应证。移植物抗宿主病（graft versus host disease,GVHD）是异基因移植后出现的毒性反应,甚至成为致命性的并发症。移植物抗肿瘤（graft versus tumor,GVT）效应是异基因移植治疗实体瘤的关键,而GVT效应常伴随GVHD的出现。因此,如何在保留GVT效应的同时降低GVHD是我们所面临挑战。目前,通过改变预处理方案、加强对移植物的处理、改变免疫抑制疗法等3种策略使用于GVHD的防治,取得了一定效果,为异基因造血干细胞移植治疗实体瘤带来了广阔前景。     

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     

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。     

急性髓系白血病患者异基因骨髓移植后复发行同一供者二次移植一例

 目的　探索血缘HLA全相合骨髓造血干细胞移植（HSCT）后复发病例进行同一供者外周血造血干细胞二次移植（HSCT2）的可行性。方法　1例急性髓系白血病（M4）患者接受血缘HLA全相合供者骨髓移植后18个月复发,染色体检查提示为受者复发型。给予CY-TBI预处理后输注同一供者外周血HSCT2,同时降低预防移植物抗宿主病（GVHD）强度。结果　患者HSCT2后获得稳定植入,患者并发急性GVHD（肠道Ⅳ级,皮肤Ⅲ级）,完全缓解至+8月。结论　对于血缘造血干细胞供者移植后复发的患者,HSCT2同一供者HSCT是可行的。     

家族相关的HLA部分不合的异基因骨髓移植

目的 :为了扩大异体造血干细胞移植供者造血干细胞的来源 ,探索 HL A部分不完全相合的家属供者的异体外周血干细胞移植治疗白血病的方法和效果 ,以克服家庭缩小 ,家族性 HL A相合供者不足的困难。方法 :对两例无 HL A相合家族供者的白血病患者进行 HL A一个位点不合的家族供者的异体外周血造血干细胞移植 ,给予抗淋巴细胞球蛋白和 FK5 0 6,以防治 GVHD。结果 :2例病人均移植成功 ,1例 HL A- A位点不合的病人顺利植入 ,未发生 GVHD。 1例 HL A- B位点不合的病人发生了 度 GVHD,经治疗后缓解。随访 >6个月均显示供者在染色体改变 ,无白血病表现。结论 :以 HL A不完全相合的家族供者进行异体造血干细胞移植治疗白血病是可行的有效方法 ,抗淋巴细胞球蛋白及 FK 5 0 6是防治 GVHD的有效方法     

7例格列卫联合非清髓造血干细胞移植治疗加速期、急变期CML的临床观察

目的探讨非清髓造血干细胞移植联合格列卫在治疗慢性粒细胞性白血病(CML)中的作用.方法7例CML患者(4例为AP,3例为BP),移植前、后口服格列卫(400～1 500mg/d)治疗,预处理方案为福达华氟达拉宾、环磷酰胺和阿糖胞苷联合ATG和(或)CD3单抗.供者HLA配型2例完全相合,2例一个位点不相合,1例3个位点不相合的同胞及2例半匹配的母亲供者,干细胞来源为G-CSF动员的外周血造血干细胞(PBSC),GVHD预防以环孢菌素A和骁悉为主,部分病例加用MTX、CD3单抗及CD25单抗(塞尼派).结果7例患者均获得不同程度的嵌合状态,3例获得完全嵌合(FC＞95%),4例获得44%～95%的混合嵌合,经调整免疫抑制剂、供者淋巴细胞/PBSC输注,格列卫治疗后,2例患者在移植后1.5～10个月转变为完全嵌合.移植后中性粒细胞＞0.5×109/L天数,16d(范围10～21d);血小板大于20×109/L天数,10d(范围4～15d).移植期间1例患者移植后45天因肠道感染,颅内出血死亡.另1例患者移植后27天因多脏器衰竭死亡.5例患者随访7～23个月,3例发生Ⅰ～ⅡGVHD,2例发生Ⅲ～ⅣGVHD,1例因cGVHD死于感染,余4例仍生存,平均无病生存12.2个月(7～17个月),Bcr/abl转阴时间33～130天,巡访期间无1例复发.结论非清髓造血干细胞移植前、后联合格列卫治疗CML,具有降低移植前白血病细胞负荷,抑制残留白血病细胞增殖,促进供者完全嵌合状态的转变,增强GVL效应的作用,是一种安全有效的治疗方法,值得进一步临床研究.     

非清髓性异基因骨髓移植治疗白血病的动物实验研究

[目的]探讨非清髓性异基因骨髓移植及加供者淋巴细胞输注治疗小鼠白血病的疗效.[方法]荷L7212白血病的615(H-2K)小鼠,于接种白血病细胞后第2天接受60Co-γ射线全身照射(TBI 8.5Gy或5Gy)分为若干组,照射当天移植供鼠BALB/C(H-2d)小鼠的骨髓细胞(5×106)和脾细胞(1.5×107),移植后第2天腹腔注射环磷酰胺(200mg/kg);供者淋巴细胞输注组分别于移植后第7天、14天、21天再次输注供鼠脾细胞5×106、1×107、2×107,观察受鼠的移植物植入、移植物抗宿主病(GVHD)、受鼠生存时间及移植相关并发症等.[结果]非清髓性预处理能保证移植物的稳定植入,非清髓性异基因骨髓移植组小鼠生存时间为22.3±4.8天,与非清髓空白组14.7±3.4天和传统移植组18.3±3.2天比较均有显著性差异(P＜0.05),供者淋巴细胞输注(DLI)组小鼠平均生存时间明显延长,为34.3±2.5天,与非清髓移植组比较均有显著性差异(P＜0.05),且无明显GVHD表现和病理学改变,移植相关并发症减少.[结论]非清髓性异基因骨髓移植能在减轻GVHD的同时保留一定的移植物抗白血病(GVL)效应,移植后行DLI可在减轻移植相关并发症的基础上进一步增强GVL效应.     

人白细胞抗原不合异基因造血干细胞移植治疗难治性重型再生障碍性贫血的临床研究

目的 探讨人白细胞抗原(HLA)不合供者异基因造血干细胞移植治疗难治性重型再生障碍性贫血(SAA)的可行性.方法 2008年5月至2009年9月,对7例SAA患者进行了8次移植,其中女3例,男4例,中位年龄14.5岁(1.4～29.0岁);从确诊至移植的中位时间为13个月(5.5 ～87.0个月);移植前均接受过1种以上的免疫抑制剂[抗胸腺细胞球蛋白(ATG)、环孢素(CsA)等]治疗3个月以上无效,完全依赖输血生存.移植前仅有2例无感染并发症,其余5例均有1个以上感染部位.预处理方案:第1例首次非血缘移植时采用环磷酰胺(CTX)加200 cGy的全身放疗,另有1例非血缘患者及1例半相合患者均采用CTX+ATG的预处理方案,其他5例(次)患者均采用CTX+氟达拉滨(Flu)+ ATG方案.造血干细胞来源:非血缘全合外周血供者2例,HLA8/10相合供者1例,均来自中华骨髓库;HLA半相合供者5例(来自母亲供者3例、父亲及胞兄各1例),均为3/6位点相合.移植物抗宿主病(GVHD)预防:自预处理开始即加用CsA及吗替麦考酚酯(MMF);移植后短暂应用甲氨蝶呤(MTX).结果 3例非血缘移植的患者中,1例稳定植入,2例被完全排斥,其中1例在排斥后半个月(+50天)再次由其母亲提供髓血混合干细胞进行移植,稳定植入,已随访11个月余,血象完全恢复正常,嵌合体检查100％供者型造血.半相合移植母供子患者中,1例白细胞和血小板稳定植入,但于+52天死于颅内真菌感染,另有1例+3天死于肺部感染.父供子的患者+11天死于败血症.胞兄供妹的患者到+30天时血象无改进,2次骨髓穿刺检查均无植入倾向,家长选择放弃治疗.GVHD发生情况:植入成功者均有Ⅰ～Ⅱ度皮肤排异,但都得到有效控制.结论 对无理想供者、免疫抑制治疗失败的SAA患者,采用CTX+Flu+ATG预处理方案行HLA不合的异基因造血干细胞移植是一种选择,值得进一步探索.     

减低强度预处理异基因造血干细胞移植治疗老年人复发难治性急性髓系白血病的临床研究

目的 探讨减低强度预处理异基因造血干细胞移植（allo-HSCT）治疗老年人复发难治性急性髓系白血病（AML）的疗效和安全性.方法 采用减低强度预处理的allo-HSCT治疗北京军区总医院2012年1月至2014年1月收治的6例老年人复发难治性AML,其中男5例,女1例,年龄61～68岁,平均年龄64.6岁,供者接受粒细胞集落刺激因子动员,均采用外周血干细胞移植,预处理方案为降低预处理强度的氟达拉滨联合白消安注射液（商品名：白舒非）、阿糖胞苷及环磷酰胺等,移植物抗宿主病（GVHD）预防采用联合免疫抑制剂,移植后3个月进行预防性供者外周血干细胞输注,观察全部患者不良反应、GVHD和无病生存等情况.结果 全部患者获造血重建,中性粒细胞≥0.5×109/L及血小板计数≥20×109/L的平均时间分别为21.5 d及24.2 d,植入证据检测证实为100％为完全供者造血.中位随访18.5个月（5～30个月）,共3例发生GVHD,GVHD死亡1例,复发死亡2例,复发时间为11.5个月（5～ 18个月）,其余3例患者仍无病生存,2年的无病生存率为50％,最长无病生存时间已达30个月.结论 减低强度预处理的allo-HSCT是复发老年人AML挽救性治疗的可行方法.     

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.     

异基因造血干细胞移植治疗血液肿瘤5例

目的；探讨基因造血干细胞移植对血液肿瘤的疗效。方法：采用异基因造血干细胞移植治疗血液肿瘤５例，包括２例第一次完全缓解（ＣＲ１）急性粒细胞白血病，１例ＣＲ１急性淋巴细胞白血病，１例急性粒细胞白血产现任昨发和１例非霍奇金氏淋巴瘤Ⅳ期ＣＲ１。其中异基因骨髓移植４例，异基因外周血造血干细胞移植１例。所有病例均采用ＴＢＩ＋ＣＹ＋ＣＣＮＵ作预处理。结果：所有病例均移植成功。２例发生急性移植抗宿主病，２例发生慢     

异基因造血干细胞移植治疗成人Ph染色体阳性急性淋巴细胞白血病的临床疗效

目的:回顾性分析异基因造血干细胞移植（allo-HSCT）治疗成人Ph染色体阳性的急性淋巴细胞白血病（Ph+ALL）的疗效。方法:收集本院自2011年9月至2018年12月行allo-HSCT的Ph+ALL成人患者29例。移植前处于CR1 23例;CR2 3例;CR3 1例;未缓解（UR）2例。无关供者相合1例,同胞全相合5例,亲缘单倍体23例。骨髓+外周血造血干细胞移植14例,外周血造血干细胞移植15例。预处理方案:白消安/环磷酰胺（Bu/Cy）者1例,TBI/Cy者13例,TBI/Flu者7例,FBA者5例,CBA者3例。21例患者移植后使用TKI维持治疗至MRD阴性后1年。结果:26例获得完全造血重建,另3例患者获得ANC重建,未获得PLT重建。中位随访时间为 13（3~54）个月,死亡10例（34.5%）,死于疾病复发者6例,死于治疗相关并发症者4例（感染2例,严重肝脏GVHD 1例,TA-TMA 1例）。复发患者中均有相关高危因素（移植前未缓解及MRD阳性）。总生存率为65.5%。预期2年DFS 60%,预期2年OS 66%。移植后使用TKI维持组及不维持组预期2年DFS分别为78% vs 46%。结论:allo-HSCT是治疗急性淋巴细胞白血病患者的有效方法,移植后使用TKI维持治疗可提高移植疗效。     

Advances in allogeneic stem cell transplantation: directing graft-versus-leukemia at solid tumors

Allogeneic stem cell transplantation was originally developed as a method to rescue hematopoietic function following high dose "myeloablative" therapy in the treatment of hematological malignancies. In the first two decades of its use, dose-intensive chemotherapy alone was credited with curing those patients who achieved sustained remission following this procedure. However, more recently investigators have come to recognize that antineoplastic effects mediated by immunocompetent donor T-cells transplanted with the stem cell allograft can be induced against hematological malignancies. Indeed, this graft-vs-leukemia (GVL) or graft-vs-tumor (GVT) effect is now felt to represent the principal modality required to sustain durable remissions of hematological malignancies following this approach. The powerful and potentially curative nature of the GVT effect in hematological cancers has recently lured oncologists into exploring the therapeutic potential of allogeneic stem cell transplantation as an investigational approach for treatment-refractory solid tumors. We review here the development and early clinical results of allogeneic stem cell transplantation as potential immunotherapy for solid tumors.     

Graft-vs.-lymphoma effect in various histologies of non-Hodgkin's lymphoma

Generally, there is a significantly lower risk of lymphoma relapse following allogeneic than after autologous stem cell transplant. Factors contributing to this lower risk of relapse include an absence of the use of ablative conditioning, with a tumor-free graft, and the generation of a graft-vs.-tumor (GVT) immune response. Allogeneic transplantation, however, has the possibility of graft-vs.-host disease (GVHD). The use of autologous and conventional allogeneic hematopoietic stem cell transplantation (HSCT) in follicular lymphoma, diffuse large cell lymphoma, chronic lymphocytic leukemia and multiple myeloma is discussed. Due to a 1-year transplant-related mortality of 30-40% and complications caused by GVHD, conventional, myeloablative, allogeneic transplantation is a high-risk option for low-grade lymphoproliferative disorders. Novel applications of allogeneic HSCT are described that take advantage of a GVT effect while reducing the risk of GVHD. Minimally myelotoxic pretransplant conditioning regimens allow host antigen-presenting cells to persist, enabling presentation of host minor histocompatibility antigens to donor T cells, causing a GVT response. Although complications may arise due to GVHD, non-myeloablative HSCT can be offered to patients previously ineligible for conventional high-dose treatment. A protocol developed in Seattle using a low-dose total body irradiation (TBI)-based conditioning regimen with immunosuppression using mycophenolate mofetil in combination with cyclosporin has been used in a multicenter trial. To overcome the problem of graft rejection fludarabine was later added to the protocol. A second protocol from a smaller trial used a preparative, conventional-dose regimen of fludarabine, given with cyclophosphamide. Rituximab was also given to provide synergistic action with the chemotherapy to enhance tumor control in the early post-transplant period to allow time for the establishment of the GVT effect. Following transplantation, GVHD prophylaxis was given using tacrolimus with methotrexate. A trial of a further variation of allogeneic HSCT, tandem auto/allo transplants, is described. First, high-dose therapy with autologous PBSC rescue was used to cytoreduce the disease. This was followed by a reduced-intensity or non-myeloablative allogeneic graft. This procedure was devised to take advantage of high-dose therapy and allogeneic HSCT. Results for non-myeloablative allogeneic HSCT are particularly promising in low-grade NHL and the GVT effect may augment response and delay or prevent relapse. However, for aggressive disease, non-myeloablative regimens are only indicated for patients with minimal disease, as the non-myeloablative regimens are unable to control the tumor before the generation of a GVT effect, and/or lack the ability to control rapidly proliferating disease. Patients with relapsed disease may require a higher-dose regimen or tandem transplant approach.     

异基因免疫治疗促进移植物抗肿瘤效应的探讨

 造血干细胞移植后细胞免疫缺陷是疾病复发的一个重要原因,同时异基因造血干细胞移植也可以认为是一种过继性免疫治疗,能克服受者细胞免疫缺陷和促进移植物抗肿瘤（GVT）效应,清除微小残留病和预防疾病复发。如何提高GVT效应仍需要进一步明确,重点介绍2011年美国血液学会（ASH）年会上相关的新进展。     

Allogeneic blood stem cell transplantation after a reduced-intensity,preparative regimen: a pilot study in patients with refractory malignancies

BACKGROUND: The immune-mediated graft-versus-tumor (GVT) effect plays a therapeutic role in the treatment of patients with hematologic malignancies who undergo allogeneic hematopoietic stem cell transplantation (HSCT). More recently, it was reported that a GVT effect also occurred in patients who underwent transplantation for metastatic renal carcinoma. The authors carried out a pilot trial of allogeneic transplantation after a reduced-intensity, preparative regimen in patients with refractory malignancies, including solid tumors. The objectives of the current study were to evaluate the feasibility of this approach in terms of toxicity and engraftment and to document evidence of GVT effects. METHODS: Seventeen patients with Stage IV malignancies (7 patients with renal cell carcinoma, 3 patients with sarcoma, 2 patients with breast carcinoma, 2 patients with Hodgkin disease, 1 patient with ovarian carcinoma, 1 patient with melanoma, and 1 patient with both melanoma and renal cell carcinoma) that were not amenable to further conventional treatment were enrolled. The median patient age was 43 years (range, 10-60 years). The Eastern Cooperative Oncology Group performance status (PS) was 0-1 in 11 patients and 2-3 in 6 patients. Preparative treatment consisted of reduced-intensity chemotherapy with fludarabine (30 mg/m(2) per day for 4 consecutive days) and cyclophosphamide (30 mg/Kg per day for 2 consecutive days) prior to allogeneic HSCT from a human leukocyte antigen-identical sibling. The median number of CD34+ cells infused was 6.06 x 10(6)/kg (range, 1.5-14.0 x 10(6)/kg). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin-A and short-term methotrexate. RESULTS: Patients who had a PS of 2-3 prior to undergoing HSCT experienced Grade 4 hematologic toxicities and Grade > or = 3 organ toxicities and died of either treatment-related complications or disease progression within 100 days from transplantation. By contrast, 10 of 11 patients who had a PS of 0-1 prior to undergoing HSCT experienced only short-lasting, Grade < or = 3 neutropenia and thrombocytopenia and no organ toxicity; 1 of 10 patients died of graft failure on Day +29 after undergoing HSCT. By Day +90, 100% donor chimerism was documented in all patients with a past history of heavy chemotherapy, whereas mixed donor chimerism was observed in the 4 patients with a past history of only 1 line of chemotherapy and/or immunotherapy prior to entering the HSCT program. Grade 2-3 acute GVHD occurred in 5 patients. Among patients with a follow-up > 100 days, 2 complete responses and 3 transitory partial responses were recorded. CONCLUSIONS: With this conditioning regimen, full donor chimerism was achieved rapidly only in patients who had received previous intensive chemotherapy. In a proportion of patients with refractory malignancies, allogeneic transplantation resulted in tumor regression. This novel therapeutic strategy may provide little benefit in patients with poor PS and rapidly progressing disease.     

造血干细胞移植治疗中高度恶性非霍奇金淋巴瘤5例

造血干细胞移植治疗非霍奇淋巴瘤５例,包括４例第 完全缓中,高度恶性ＮＨＬ;１例高度恶性ＮＨＬ合并淋巴瘤白血病。其中自体骨髓移植４例,异基因外周血干细胞移植１例。所有病例的移植成功。４例ＡＢＭＴ患者已无病生存５０,４８,３９和３个月,１例ａｌｌｏ－ＰＢＳＣＴ发生慢性移植物抗宿主病,移植后１２人月死于白血病复发。结果显示ＡＢＭＴ是治疗中,高度恶性ＮＨＬ有效手段。     

伊达比星加强预处理异基因造血干细胞移植治疗难治性急性髓系白血病的临床研究

 　目的　探讨预处理方案中加伊达比星增强预处理的异基因造血干细胞移植（allo-HSCT）治疗难治性急性髓系白血病的疗效和安全性。方法　选择北京军区总医院血液科2010年8月至2012年12月在预处理方案中增加伊达比星的allo-HSCT治疗的27例难治性急性髓系白血病患者,其中男13例,女14例,年龄2～53岁,平均年龄24.6岁;FAB分型包括M1型1例,M2型10例,M3型1例,M4型1例,M5型11例,M6型3例;移植时复发未缓解18例,复发后取得2次或者3次缓解9例;22例采用骨髓加外周血干细胞联合移植,5例仅采用外周血干细胞移植;预处理方案为在以氟达拉滨替代环磷酰胺的改良白消安＋环磷酰胺方案基础上,加用伊达比星（15 mg／m2,连续用3 d）,移植后观察患者不良反应、并发症和无病生存等情况。结果　全部患者均获重建造血,能较好耐受此预处理方案,无因预处理相关不良反应而早期死亡者,未发生心脏毒性事件,移植后粒细胞植活平均时间为15 d（11～23 d）,植入证据示均为完全供者造血。随访至2013年5月,中位随访时间12个月（5～33个月）,13例发生急性GVHD,11例发生慢性GVHD,因急性GVHD死亡2例,发生严重感染的13例中死亡1例,复发的7例中死亡5例;共死亡8例,其余19例患者生存。全组患者治疗相关死亡率、复发相关死亡率和总体生存率分别为11.1 %（3／27）、18.5 %（5／27）和70.4 %（19／27）。结论　allo-HSCT预处理方案中加入伊达比星的增强方案安全可行,患者耐受良好,可降低难治性白血病的复发率,提高长期生存率,移植后并发症并未增加。     

The allogeneic effect in non-Hodgkin's lymphoma

Allogeneic hematopoietic stem cell transplantation (HSCT) has been restricted to medically fit patients under the age of 55 years due to adverse effects of the intensive conditioning regimens. Autologous HSCT has not proven to be a particularly effective treatment for patients with low-grade non-Hodgkin's lymphoma (NHL). Much of the benefit of allogeneic HSCT appears to be mediated by a graft-vs.-tumor (GVT) effect. Reduced-intensity regimens in allogeneic HSCT have been developed to minimize conditioning regimen-related toxicities and to control the malignancy until a GVT effect is established. A number of studies investigating reduced-intensity allogeneic HSCT are discussed. Results from these studies suggest that indications for allogeneic transplant include patients with low-grade NHL with a sibling or matched donor who are under 60 years of age; young patients with mantle cell lymphoma who are in first remission and have a sibling or matched donor; patients with high-grade NHL who have already failed an autograft but have chemosensitive disease, and those under 30 years of age who have poor-risk disease and are in first remission. It is concluded that reduction in treatment-related mortality with reduced-intensity HSCT and the presence of GVT effects increases the applicability of allogeneic transplantation for NHL. However, treatment will be improved by optimizating conditioning regimens and a better understanding of patient selection criteria and the immune processes involved in graft-vs.-host disease and GVT.     

Nonmyeloablative allogeneic hematopoietic stem cell transplantation for metastatic breast cancer

Previously, there was very little interest in investigating allogeneic hematopoietic stem cell transplantation (alloHSCT) in breast cancer because of the significant morbidity and mortality associated with this procedure, as well as the disappointing results observed in clinical trials with high-dose chemotherapy and autologous hematopoietic stem cell transplantation in advanced breast cancer. However, the development of nonmyeloablative (reduced-intensity) conditioning regimens, which have less treatment-related mortality but preserve the T cell-mediated graft-versus-tumor (GVT) effect, has led to the investigation of nonmyeloablative alloHSCT in diseases that had not previously been considered for conventional alloHSCT, including metastatic breast cancer. Laboratory data demonstrate that T cell-mediated responses to breast cancer that inhibit tumor growth are possible and provide the rationale to pursue allogeneic adoptive cellular therapy as a strategy to eliminate breast cancer. Early reports of nonmyeloablative alloHSCT indicate that a clinical GVT effect against breast cancer does exist. The responses appear to be dependent on the development of complete donor lymphoid chimerism, and responses may be delayed. The results from these initial trials must be interpreted cautiously. It is unlikely that nonmyeloablative alloHSCT by itself will result in complete eradication of metastatic breast cancer; however, it may serve as a therapeutic platform to enhance the effects of currently available immunotherapies (eg, trastuzumab administration) and complement existing cytotoxic therapies. Well-designed studies will be necessary to determine the clinical efficacy of nonmyeloablative alloHSCT as adoptive cellular therapy in metastatic breast cancer.