减低预处理剂量异基因造血干细胞移植后的白血病复发

目的：减低预处理剂量异基因造血干细胞移植预处理方案剂量强度弱于清髓性移植且又强于真正的非清髓移植，期望在降低毒副反应的同时能够减少复发。评价减低预处理剂量的异基因造血干细胞移植后白血病的复发情况及主要影响因素。 方法：①对象：选取2003—03／2005—06厦门大学附属中山医院血液科收治的23例白血病患者，急性粒细胞白血病6例，急性淋巴细胞白血病7例，慢性粒细胞白血病10例。供者同胞HLA全相合10例，同胞或亲缘供者不全相合12例，非血缘1例。供受者对治疗均签署知情同意书，实验经医院医学伦理委员会批准。②实验方法：23例白血病患者均采用减低预处理剂量方案，马利兰4mg/（kg·d），2-3d；环磷酰胺50mg／（kg·d），2d。其中19例患者在上述方案的基础上加用氟达拉滨30mg／（m^2·d），3-5d；10例患者同时加用阿糖胞苷（1．0～2．0）g／（m^2·d），1～3d。供受者HLA位点不合时用兔抗胸腺细胞球蛋白（3．0～5．0）mg/（kg·d），3-5d。异基因造血干细胞移植前行供者外周血干细胞动员，4-5d后连续采集2次，23例白血病患者输入CD34^＋细胞中位数为4．02×10^6／kg。采用骁悉＋环孢素＋短程甲氨喋呤方案预防移植物抗宿主病。③实验评估：采用STR—PCR方法检测异基因造血干细胞植入证据。 结果：①造血功能重建检测：23例患者均顺利完成造血功能重建，无一例发生预处理相关死亡。经预处理后外周血白细胞最低值为（0．01～0．30）×10^9L^-1，血小板最低值为（5～20）×10^9L^-1；中性粒细胞恢复到0．5×10^9L^-1的中位时间为术后11d，血小板恢复到30×10^9L^-1的中位时间为术后12d。术后30d经STR—PCR检测22例患者为完全供者型，骨髓象均完全缓解，剩余1例复发患者未行STR—PCR检测。②移植物抗宿主病发生情况：23例患者中，9例（39．1     

减低强度预处理异基因造血干细胞移植治疗多发性骨髓瘤的临床研究

本研究探讨减低强度预处理异基因造血干细胞移植(allo-HSCT)治疗多发性骨髓瘤(MM)的疗效和安全性。采用减低强度预处理的allo-HSCT治疗北京军区总医院2011年1月至2012年1月收治的3例多发性骨髓瘤患者,供者全部为HLA全相合亲缘性同胞,供者接受粒细胞集落刺激因子(G-CSF)动员,采用骨髓加外周血干细胞联合移植,预处理方案为降低预处理强度的氟达拉滨联合马法兰及抗人胸腺细胞球蛋白等,移植物抗宿主病(GVHD)预防采用经典的环孢菌素A(CsA)联合氨甲蝶呤(MTX),移植后3个月进行预防性供者外周血干细胞输注,输注单个核细胞数(MNC)为0.2×108/kg,移植后观察患者毒副反应、GVHD和无病生存等情况。结果显示:3例患者均获造血重建,中性粒细胞数≥0.5×109/L及血小板数≥20×109/L的平均时间分别14.3 d及15.3 d,植入证据检测为100%完全供者造血,随访至2013年1月,中位随访时间13个月(12-15个月),无1例合并GVHD、感染等严重并发症,全部患者目前仍处于完全缓解状态,最长无病生存时间已达15个月。结论:减低强度预处理的allo-HSCT对MM是一个有效方法,该方案安全系数大、疗效确切,早期进行移植完全缓解率高,患者有可能长期生存。该方案可作为MM治疗的关键技术在临床广泛开展。     

减低剂量预处理的异基因造血干细胞移植治疗难治性白血病20例分析

目的 观察减低剂量预处理的异基因造血干细胞移植(allo-HSCT)对难治性白血病未缓解期的疗效.方法 20例未缓解期难治性白血病患者,采用以氟达拉滨(Flud)联合小到中等剂量的全身照射(TBI)治疗为基础的减低剂量的预处理方案行allo-HSCT.采用环孢素A加霉酚酸酯或短程甲氨蝶呤,或三种药物联合应用预防移植物抗宿主病(GVHD),部分患者还加用了CD52单抗、CD25单抗或抗胸腺细胞球蛋白.结果 17例患者造血细胞成功植入,中性粒细胞＞0.5 × 109 /L的中位时间为13(11～17)d,血小板＞50×109 /L的中位时间为19(11～42)d.外周血T细胞短串联重复序列PCR检测,16例达到完全供者嵌合,中位时间为14(7～42)d.急性GVHD发生率为47.1%(17例中8例),慢性GVHD的发生率为38.5%(13例中5例).移植相关死亡率25.0%(20例中5例),死亡原因主要为植入失败、颅内出血和严重感染.7例血液学复发,目前无病存活9例,Kaplan-Meier法分析全组患者2年总体生存率为(35.3±14.2)%;而其巾急性非淋巴细胞白血病患者2年总体生存率为(52.5±18.6)%.结论 以Flud联合TBI为基础的减低剂量的allo-HSCT预处理方案,耐受性好,移植相关死亡率低,能够用于治疗难治性白血病,并有可能通过降低移植相关死亡率提高总体生存率,急性非淋巴细胞白血病预后优于急性淋巴细胞白血病患者.     

异基因造血干细胞移植治疗白血病9例

重庆医科大学附属第一医院血液内科2007-01/2008-04应用异基因造血干细胞移植治疗白血病患者9例,6例急性髓细胞性白血病,3例慢性髓系白血病;供者中6例为HLA完全相合的同胞,2例为HLA9/10相合的无关供者,1例为半相合供者;预处理采用经典的BU/CY方案或GIAC方案;移植物抗宿主病的预防采用环孢菌素A＋吗替麦考酚酯＋甲氨喋呤方案或环孢菌素A＋吗替麦考酚酯＋甲氨喋呤＋抗胸腺细胞球蛋白方案。结果全部患者均获得造血重建,中性粒细胞≥0.5×10^9L^-1、血小板〉20×10^9L^-1的中位时间分别是11,15d;无急性移植物抗宿主病发生,1例发生慢性移植物抗宿主病;随访3-16个月无病生存率为77.8%。死亡2例。     

减低强度预处理的异基因造血干细胞移植治疗复发ETO阳性急性髓系白血病的临床研究

本研究旨在探讨减低强度预处理的异基因造血干细胞移植（allo-HSCT）治疗复发ETO阳性急性髓系白血病（AML）的疗效和安全性.采用减低强度预处理的allo-HSCT治疗2010年1月至2013年1月在北京军区总医院收治的15例复发ETO阳性急性髓系白血病患者,全部为复发或难治性高危类型,其中男10例,女5例,年龄16-48岁,平均年龄32.5岁;移植前6例为缓解状态,9例为未缓解状态,10例为HLA配型全相合,5例为HLA配型半相合.全部病例均采用外周血干细胞移植,供者接受粒细胞集落刺激因子动员.预处理方案为降低预处理强度的氟达拉滨联合白舒非、阿糖胞苷及环磷酰胺.移植物抗宿主病（GVHD）预防采用免疫抑制剂,包括环孢素A、氨甲蝶呤、他克莫司等,移植后3个月进行预防性供者外周血干细胞输注,观察全部患者毒副反应、GVHD和无病生存等情况.结果表明：全部患者均获造血重建,中性粒细胞≥0.5×109/L及血小板≥20×109/L的平均时间分别为15.5 d及16.8 d,植入证据检测证实为100％为完全供者造血.随访至2014年6月,中位随访27.5个月（18-54个月）;全部病例中发生GVHD8例,因并发症死亡1例,复发死亡4例,其余10例患者仍无病存活,2年的无病生存率为66.7％,最长无病生存时间已达54个月.结论：减低强度预处理的allo-HSCT挽救性治疗复发ETO阳性急性髓系白血病具有良好疗效,安全系数大,可作为关键技术在临床广泛开展.     

关于急性白血病异基因造血干细胞移植后复发的防治

随着异基因造血干细胞移植（allo—HCT）技术的不断成熟与提高，allo—HCT已成为治愈急性白血病（AL）的主要乃至唯一选择。然而移植后约25％～30％的患者仍然复发，特别是高危型AL患者移植后复发率可高达40％或以上，占移植后死亡原因的首位。因此针对移植后复发的防治策略的研究是提高allo—HCT疗效的迫切需要。     

异基因造血干细胞移植后白血病复发伴活动性移植物抗宿主病患者的临床研究

目的 探讨异基因造血干细胞移植(allo-HSCT)后白血病复发伴活动性移植物抗宿主病(GVHD)患者GVHD与GVL效应的分离.方法 分析11例接受allo-HSCT后在白血病复发时存在活动性GVHD的患者其原发病、疾病状态、复发时GVHD类型、供者淋巴细胞输注(DLI)疗效及转归等对GVL效应的影响.结果 11例患者包括急性淋巴细胞白血病5例,急性髓系白血病6例,其中5例曾行预防性DLI,复发时伴有活动性DLI后GVHD,包括2例Ⅱ度急性GVHD(aGVHD),1例原局限型慢性GVHD(cGVHD)加重+新发Ⅱ度aGVHD,2例广泛型cGVHD;这5例患者复发后,2例行化疗+治疗性DLI,DLI后在广泛型cGVHD反复加重情况下,1例达完全缓解(CR)后再次复发,1例未达CR.另6例患者复发前未行预防性DLI,白血病复发时亦均存在活动性GVHD,包括3例广泛型cGVHD、1例Ⅰ度aGVHD及2例Ⅲ～Ⅳ度aGVHD,复发后行化疗+治疗性DLI,之后2例达CR后再次复发,4例未达CR.结论 allo-HSCT后活动性GVHD不一定伴随可抑制白血病复发的有效GVL效应.     

减低剂量预处理方案在亲缘HLA单倍体相合造血干细胞移植中的应用

背景:近年来减低剂量预处理异基因造血干细胞移植已被证明是安全有效的治疗手段,在同胞全相合和无关供者中应用逐年增多,它特别适合老年人或年轻人合并器官功能障碍的患者,然而由于找到HLA配型相合供体的概率不高,使得同胞全相合和无关供者减低剂量预处理异基因造血干细胞移植开展受限,而HLA不相合/单倍体供体则可以迅速找到,但减低剂量预处理的单倍体造血干细胞移植应用的报道还较少,国内尚未见报道,因此对减低剂量预处理的单倍体造血干细胞移植的开展情况进行综述非常重要。目的:综述减低剂量预处理在亲缘HLA单倍体造血干细胞移植中的应用现状。方法:以"减低剂量预处理方案、非清髓性预处理方案、HLA单倍体相合、造血干细胞移植和No-nmyeloablative conditioning,Reduced-intensity conditioning,HLA-haploidentical,Hematopoietic stem cell transplantation"为检索词,应用计算机检索1997至2014年万方数据库、CNKI和PubM ed数据库、外文医学信息资源检索平台检索关于减低剂量预处理在亲缘HLA单倍体造血干细胞移植中应用的相关文献,根据纳入标准和排除标准,最终选取25篇文献进行分析,全部为英文。结果与结论:减低剂量预处理异基因造血干细胞移植在HLA同胞全相合及无关供者中开展的较多且效果愈来愈好。减低剂量预处理的单倍体造血干细胞移植开展的较晚且报道较少,其植入、感染、移植相关死亡、移植物抗宿主病、长期无病生存率和总生存率等各个研究的结果差异较大,早期结果稍差,而近期总体情况有明显改善。目前看减低剂量预处理的单倍体造血干细胞移植是可行的,尤其对于找不到同胞相合及无关全相合供者的患者来说,HLA单倍体相合的血缘关系亲属成为最有潜力的干细胞来源。减低剂量预处理的单倍体造血干细胞移植保留较强的移植物抗白血病效应,且寻找供者容易,有足够的细胞后续治疗如供者淋巴细胞输注,同时通过发挥移植物抗白血病效应,可有效清除患者体内的肿瘤细胞,为处在疾病进展期或经历多次治疗失败的患者,尤其是老年患者、合并器官功能障碍及并发症患者,提供有效的挽救治疗手段。但由于开展的时间较短,今后在应用中该如何选择最佳方案、最佳时机以及减低移植物抗宿主病、移植相关死亡率及复发率等尚需进一步深入的研究。     

第二次移植治疗异基因造血干细胞移植后复发白血病的临床研究

目的　评价第二次异基因造血干细胞移植 (allo HSCT)治疗allo HSCT后复发白血病的疗效。方法　回顾分析因allo HSCT后复发而进行第二次allo HSCT的 1 0例白血病患者临床资料。其中急性髓系白血病 5例 ,急性淋巴细胞白血病 4例 ,慢性髓系白血病 1例。第一次HSCT后中位复发时间 1 4 1d(34～ 5 4 5d)。第二次HSCT时预处理方案包括 :以中剂量阿糖胞苷 (Ara C)为主的联合化疗 5例 ;以白消安为主的联合化疗 3例 ;含常规剂量Ara C的联合化疗 1例 ;氟达拉宾 /马法兰 1例。移植物抗宿主病 (GVHD)预防方案 :单用环孢菌素 (CsA) 2例 ,CsA 短疗程甲氨蝶呤 1例 ,短疗程他克莫司 1例 ,6例未预防。输注外周血单个核细胞中位数 6 .1× 1 0 8/kg[(1 .9～ 1 1 .8)× 1 0 8/kg]。 结果　可评价的 8例患者均造血重建 ,达中性粒细胞绝对值 >0 .5× 1 0 9/L、血小板 >2 0× 1 0 9/L中位时间分别为移植后 1 1d(3～ 1 7d)、1 2d(9～ 2 3d)。发生Ⅰ度急性GVHD 4例 ,Ⅱ度急性GVHD 3例。可评价的 6例中 5例发生局限型慢性GVHD。 2例无病生存 986d和 1 91 3d。移植相关死亡 5例。复发 3例 ,均死亡。 2年实际无病生存率、移植相关死亡率、复发率分别为 2 0 %、5 0 %和 30 %。结论　第二次allo HSCT是治疗allo HSCT后复发白血病的有效     

异基因造血干细胞移植后白血病复发的治疗

异基因造血于细胞移植（allo—HSCT）是治疗急、慢性白血病的有效手段，近年来，随着HLA配型技术的进步，新型免疫抑制剂的采用，减低移植预处理剂量／非清髓移植等预处理方法的改进，以及对各类感染等并发症防治手段的增加，移植相关并发症和移植相关死亡率（TRM）明显下降，急性白血病缓解期行allo—HSCT后和3～5年生存率达到50％～70％，慢性髓细胞白血病（CML）移植后的3～5年生存率达到60％～85％，但移植后原发病的复发仍然是影响治疗成功的最主要的因素。根据国际外周血和骨髓移植登记研究中心（CIBMTR）的资料，1998年～2002年间所进行的自体移植患者死亡原因中，复发占75％，而HLA相合同胞供体（MSD）移植和非血缘关系供体（MUD）移植后死亡原因中，复发分别占38％和32％，均居各类致死因素之首。因此，如何预防和治疗移植后的复发，仍然是提高造血干细胞移植疗效的最重要的课题之一。     

Severe fludarabine neurotoxicity after reduced intensity conditioning regimen to allogeneic hematopoietic stem cell transplantation: a case report

We present a case of severe, irreversible neurotoxicity in a 55‐year‐old‐patient with myelofibrosis undergoing hematopoietic stem cell transplantation following a reduced intensity conditioning including fludarabine. The patient developed progressive sensory‐motor, visual and consciousness disturbances, eventually leading to death. MRI imaging pattern was unique and attributable to fludarabine neurotoxicity.     

异基因造血干细胞移植后发生阻塞性肺病的临床特征

目的:分析异基因造血干细胞移植后阻塞性肺病的临床特点和发病因素。方法:厦门大学附属中山医院血液科于2002-12/2005-04对27例血液病患者进行了异基因造血干细胞移植。移植前均无肺部疾患史,胸部X射线检查肺功能均正常。随诊截止时间为2006-04-30。预处理均采用以马利兰 环磷酰胺为基础的方案,预防移植物抗宿主病采用骁悉、环孢素及短程甲氨喋呤方案,移植前给予更昔洛韦预防巨细胞病毒感染。阻塞性肺疾病诊断标准:有呼吸道症状(干咳、呼吸困难)但无严重感染证据,肺功能指标:1s用力呼气量小于预计值的80%及1s用力呼气量/用力肺活量小于80%,胸部X线片显示可正常或过度通气,高分辨CT可表现为弥漫性肺泡实变,支气管、细支气管扩张。分析患有阻塞性肺病患者的造血功能重建情况、移植物抗宿主病发生情况、阻塞性肺病的发生情况、治疗及预后情况。结果:27例患者均进入结果分析。①根据临床诊断标准,7例患者患有阻塞性肺病,发生率为26%,中位发病时间为移植后300d(110～390d),均伴有慢性移植物抗宿主病。②主要表现为干嗽(57%),呼吸困难、双肺呼吸音弱(100%),胸片未见异常,胸部高分辨CT分别显示正常、下肺少量较淡的模糊小片状影及支气管扩张;肺功能均显示重度混合性通气功能障碍。③抗生素治疗无效,免疫抑制剂及激素治疗有效,但于减量或停药后症状可加重,3例死于呼吸衰竭,4例症状好转,但肺功能无改善。结论:阻塞性肺病是移植后严重并发症之一,部分为进行性发展,死亡率较高,定期的肺功能检查有助于早期诊断;其原因可能主要为非感染性因素所致。     

Reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation

Chemotherapy and radiotherapy administered in preparation for allogeneic hematopoietic progenitor cell transplantation serve the dual role of providing antitumor activity as well as immunosuppression to prevent graft rejection. Conditioning regimens were initially designed to provide dose-intense therapy in order to overcome tumor resistance. These forms of transplants, referred to as ablative regimens, often result in significant extramedullary toxicity, limiting its applicability to younger, fitter patients. Reduced-intensity conditioning (RIC) transplants are a direct result of an understanding of the immunotherapeutic potential of the donated hematopoietic stem cells. These forms of transplants administer chemoradiotherapy with the intent of allowing for donor cell engraftment with less of an emphasis on dose intensity. In so doing, treatment-related mortality has been reduced, and older-aged patients and those with co-morbidities are now frequently offered this therapy. In the decade since its creation, RIC transplantation has changed the spectrum of patients with malignancies who may benefit from this therapy. For the first time, transplant patients are becoming more representative of the populations most at risk for diseases requiring this therapy. This article reviews the science behind RIC transplants and provides a concise summary of the current body of evidence for the major indications for which it is most commonly employed. The data presented will demonstrate that age should no longer be the sole deciding factor for referral for allogeneic transplant.     

Decreased RBCTs after reduced intensity conditioning allogeneic stem cell transplantation: predictive value of prior Hb level

BACKGROUND: RBCT (RBCT) requirements of stem cell transplant (SCT) recipients are often substantial and may be related to transplant type. STUDY DESIGN AND METHODS: An analysis was done of RBCT requirements and Hb recovery kinetic in the first 60 days after HLA-identical sibling allogeneic SCT in a series of 110 consecutive patients treated for various malignant diagnoses. Patients were prepared with either an antithymocyte globulin (ATG) and reduced intensity chemotherapy-based conditioning (RIC) (n=64) or a myeloablative conditioning regimens (MAC; n=46). Patients received marrow (n=64) or PBPCs (n=46). RESULTS: Overall, intensity of conditioning regimen (RIC vs. MAC; p=0.0005) and graft source (PBPC vs. marrow; p<0.0001) independently predicted RBCT requirements. Hb recovery was accelerated after RIC when compared to MAC allo-SCT (p=0.02). In RIC patients, RBCTs were inversely correlated to Hb level before conditioning (p<0.0001) and the dose of ATG (p=0.009). Moreover, Hb level before allo-SCT significantly influenced Hb recovery kinetic after RIC but had no impact on RBCT requirements and Hb recovery after MAC. CONCLUSION: Thus, RIC conditioning creates a different pattern of erythropoiesis recovery as compared to a MAC regimen and suggest a need for studies aimed at further reducing RBCT and accelerating Hb recovery.     

Unrelated donor transplantation after reduced intensity conditioning as an approach for patients lacking related donors for allogeneic stem cell transplantation

Allogeneic stem cell transplantation (SCT) after reduced intensity conditioning (RIC) provides a new curative treatment option for patients usually not eligible for allogeneic SCT. Because the majority of patients lack HLA-identical sibling donors (SD), unrelated donor (UD) transplantation is performed increasingly. In this retrospective analysis, we have reviewed our experience with reduced-intensity conditioning regimens, comparing related and unrelated donors. From November, 1997, to February, 2002, 51 patients with hematological malignancies received allogeneic SCT after various RIC regimens. A total of 31 had a related donor, and the remaining 20 had an unrelated donor (UD). Both groups were comparable with respect to age and gender. We observed a trend toward higher rate of graft failure in the unrelated donor group with 11% compared to 3% in the related donor group (p = 0.55). The rate of acute graft-versus-host disease (GVHD) II-IV was 36% in the RD group versus 44% for the UD group; severe GVHD III-IV occurred in 26% and 22%, respectively. There were more serious infections in the unrelated donor group with 25% compared to 16%. Transplant-related mortality was 13% (RD group) versus 30% (UD group). At 21 months, progression-free survival was 30% in both groups. The Kaplan Meier estimate of overall survival was 40% (RD) and 30% (UD group). In summary, we found no statistically significant difference regarding progression free and overall survival, despite a trend for more graft failure and increased transplant-related complications associated with the use of stem cells from unrelated donors.     

Impact of ABO incompatibility on allogeneic peripheral blood progenitor cell transplantation after reduced intensity conditioning

BACKGROUND: Most studies indicate that ABO incompatibility has no effect on the clinical outcome after allogeneic peripheral blood progenitor cell (PBPC) transplantation (allo-PBPCT). However, it carries additional risks of hemolytic reactions, delayed red blood cell (RBC) engraftment, and pure red cell aplasia (PRCA). Data on these events after reduced intensity conditioning (RIC) regimens are limited, but recent studies have suggested a higher transplant-related mortality (TRM) and morbidity in this setting. STUDY DESIGN AND METHODS: We investigated the impact of ABO-matching on the outcome of 77 patients included in a prospective RIC allo-PBPCT protocol, focusing on engraftment, transfusion requirements, graft-versus-host disease, TRM, and survival. RESULTS: There were 17 (22%) minor and 8 (10%) major ABO-incompatible transplants. No graft failures were observed. After major ABO-incompatible grafts, RBC engraftment was delayed, longer thrombocytopenia periods were documented, and transfusion requirements increased. A transient mild hemolysis occurred in 10 patients, 7 (41%) minor and 3 (37%) major ABO-mismatched. A PRCA was observed in a O+ patient with a pretransplant anti-Jka, grafted from an A + Jka+ donor. Graft-versus-host disease, disease progression, and TRM were not affected by ABO matching. CONCLUSION: ABO incompatibility was not associated with clinically relevant hemolysis after the RIC protocol used and did not impair the clinical outcome. PRCA was only observed in one patient, with a non-ABO RBC allo-antibody.     

改良马利兰-环磷酰胺2预处理方案在异基因造血干细胞移植中的应用

目的探讨改良马利兰-环磷酰胺2(Bu-CTX2)预处理方案在异基因造血干细胞移植(allo-HSCT)治疗恶性血液病的疗效。方法采用阿糖胞苷(Ara-c)、Bu或白消安针剂(白舒非)、CTX、甲基环己亚硝脲(Me-CCNU)及抗胸腺细胞球蛋白(ATG)联合作为改良Bu-CTX2预处理方案行allo-HSCT治疗恶性血液病15例。结果全部患者均顺利植入干细胞,白细胞>1.0×109/L的中位时间16.3天(+12～+20天),血小板>20×109/L的中位时间28.3天(+20～+51天);15例患者中出现全身急性移植物抗宿主病(aGVHD)Ⅳ度1例,aGVHDⅡ度2例,无Ⅲ度aGVHD发生,aGVHDⅡ～Ⅳ度的发生率20.0%,Ⅲ～Ⅳ度的发生率6.7%,随访中位时间为30.7(4～65)个月;无预处理相关死亡,无复发。结论采用改良Bu-CTX2预处理方案行allo-HSCT治疗恶性血液病是安全有效的方法 。     

Clinical developments in reduced intensity haematopoietic stem cell transplantation

Reduced intensity conditioning regimens prior to allogeneic haematopoietic stem cell transplantation (HSCT) were first described in the 1970s, and have developed rapidly over the past few years to become an important consideration as immunological therapy for patients with haematological and selected solid organ malignancies. This is especially the case for patients considered ineligible for conventional allogeneic HSCT due to age or medical contraindications. With the development of minimally toxic conditioning regimens, additional potential applications include the provision of normal haematopoietic repopulating cells to patients who have an inherited gene defect such as an haemoglobinopathy or an inborn error of metabolism. Intensive investigation in stem cell research promises to provide dramatic new insights into human biology, paving the way for new therapeutic approaches to malignant and inherited disorders.