非亲缘异基因造血干细胞移植治疗白血病患者疗效观察

目的探讨非亲缘异基因造血干细胞移植(URD-HSCT)治疗白血病的效果。方法 10例白血病患者(急性髓细胞白血病第1次缓解期3例,急性淋巴细胞白血病第1次缓解期3例、第2次缓解期1例,慢性髓细胞白血病慢性期3例)接受URD-HSCT治疗。所有患者均采用经典的或改良的白消安联合环磷酰胺预处理方案。4例采用环孢素+短程甲氨蝶呤+吗替麦考酚酯预防移植物抗宿主病(GVHD),另6例患者加用抗胸腺细胞免疫球蛋白。输注供者有核细胞中位数为5.6×108/kg,CD34+细胞中位数为3.3×106/kg。结果除1例在移植后早期死亡不能评估外,其余9例均证实植活。发生急性GVHDⅠ度3例和Ⅱ度、Ⅲ度、Ⅳ度各1例,局限性慢性GVHD7例;发生真菌感染4例、CMV血症3例、出血性膀胱炎3例。10例患者目前无病存活7例,生存期为3个月～10年。结论 URD-HSCT安全而耐受性好,移植相关并发症仍是影响URD-HSCT效果的主要问题。     

肾移植联合造血干细胞移植诱导治疗七例

目的 探讨肾移植联合造血干细胞移植诱导治疗的安全性和有效性,并总结其经验.方法 2009年实施7例亲属活体肾移植联合造血干细胞移植,其中1例为供受者HLA抗原全相合,其余为半相合.肾移植前5d使用粒细胞集落刺激因子动员供者造血干细胞,术前1d采集供者造血干细胞.肾移植前3d受者开始接受全身淋巴照射,连续3d,肾移植术中给予受者抗胸腺细胞球蛋白50 mg,术后第2、4、6天输注供者造血干细胞.术后常规采用三联免疫抑制方案,监测受者血常规、淋巴细胞亚型变化及移植肾功能等情况.结果 全身淋巴照射后受者淋巴细胞数进行性降低,以B淋巴细胞(CD19+)的比例下降幅度最大,其他血细胞数量变化不大.HLA全相合受者诱导出30％～50％的嵌合体,其余受者仅诱导出1％～5％的嵌合体.术后随访3年,7例受者移植肾功能稳定,均未出现骨髓抑制和移植物抗宿主病,未增加感染风险.经移植肾活检证实,1例受者出现轻度急性排斥反应,其余6例受者未发生排斥发生.7例受者中,有3例减少了免疫抑制剂的用量.结论 肾移植联合造血干细胞移植诱导治疗的方案安全、有效.     

输注供者自然杀伤细胞对小鼠单倍型相合造血干细胞移植的影响

目的 探讨输注供者自然杀伤(NK)细胞对小鼠单倍型相合造血干细胞移植的影响.方法 选取C57BL/6(H-2b)雄性小鼠为供者、CB6F1(H-2d/b)雌性小鼠为受者.移植前制备供者的骨髓细胞(BMC)、脾细胞(SC)及脾NK细胞,NK细胞经体外培养扩增和激活;所有受者均接受直线加速器X线全身照射(TBI)预处理.TBI后将受者分为4组(每组10只),分别进行单倍型相合造血干细胞移植.单纯TBI组:TBI后不输注细胞,仅作为对照;单纯BMC输注组:输注5×106个BMC;诱发GVHD组:输注5×106个BMC+1.5×107个SC;NK细胞输注组:输注5 x 106个BMC+1.5×107个SC+1×107个NK细胞,并腹腔注射100 ng重组人白细胞介素2(rhIL-2)和1μg rhIL-15,持续7 d.移植后观察各组受者GVHD的发生情况,并对各组受者进行组织病理学、供者细胞嵌合度和免疫功能重建等检测.另取TBI后受者20只,设白血病复发组和白血病治疗组,每组10只.白血病复发组:输注5×106个BMC+1×107个SC+2×106个白血病细胞株EL9611;白血病治疗组:在白血病复发组的基础上再输注1 x 107个NK细胞,并腹腔注射100 ng rhIL-2和1μg rhIL-15,持续7 d.观察两组受者白血病复发情况和移植后100 d的存活率.结果 单纯BMC输注组受者无GVHD发生,NK细胞输注组受者GVHD的评分和组织病理学改变均较诱发GVHD组轻(P<0.05)f诱发GVHD组的免疫功能重建较NK细胞输注组延迟.白血病复发组和白血病治疗组移植后100 d的存活率分别为20%和90%,两组比较,差异有统计学意义(P<0.01).结论 输注激活的供者NK细胞可以减轻小鼠单倍型相合造血干细胞移植后的GVHD,减少白血病复发,促进免疫功能重建.     

ABO血型不合对同胞异基因外周血干细胞移植的影响

目的探讨HLA配型相合但ABO血型不合的同胞异基因外周血干细胞移植(allo- PBSCT)治疗血液恶性肿瘤的疗效。方法对2001年6月至2005年9月的68例HLA配型相合的血液恶性肿瘤患者进行同胞allo-PBSCT,其中ABO血型不合30例(血型不合组),ABO血型相合38例(血型相合组)。急性髓细胞白血病(AML)、骨髓增生异常综合征(MDS)和慢性粒细胞白血病(CML)患者采用马利兰(BU)/环磷酰胺(CY)预处理方案；急性淋巴细胞白血病(ALL)和非霍奇金氏淋巴瘤(NHL)患者采用全身照射(TBI)/CY方案；多发性骨髓瘤(MM)患者采用TBI/CY/马法兰方案。移植物抗宿主病(GVHD)的预防采用霉酚酸酯(MMF)、环孢素A(CsA)和短程甲氨喋呤(MTX)三联方案。结果(1)除1例植入失败外,其余67例患者全部造血重建。中性粒细胞绝对值≥0．5×10~9/L和血小板数≥20×10~9/L的平均时间为移植后+12(+9～+15)d和+21(+15～+40)d,血型不合组与血型相合组植入的时间差异无统计学意义(P＞0．05)。(2)血型不合组均未出现急性溶血反应,但与血型相合组比较,红系造血延迟,在供/受者血型为A/O的7例患者中有3例(42．9%)发生纯红细胞再生障碍性贫血(PRCA)。血型不合组于移植后60d(24～153 d)血型成功转变为供者型。(3)随访至2005年9月30日,血型不合组急性GVHD发生率(20．0%)比血型相合组(2．6%)高(P=0．019),但慢性GVHD发生率、肝静脉栓塞综合征(VOD)发生率、巨细胞病毒(CMV)感染发生率、出血性膀胱炎(HC)发生率、疾病复发率及死亡率与血型相合组比较,差异无统计学意义(P＞0．05)。(4)用Kaplan-Meier生存分析发现,血型相合组和血型不合组患者之间预期4年的生存率差异无统计学意义(P＞0．05)。结论ABO血型不合可以进行allo-PBSCT,并且不影响干细胞移植的植活,虽然急性GVHD的发生率较血型相合组高,但其对复发率、死亡率及生存率无显著影响。     

高危造血干细胞移植患者应用氟达拉滨替代环磷酰胺行预处理12例

目的 探讨氟达拉滨(Flu)替代环磷酰胺(Cy)的预处理方案在异基因造血干细胞移植(allo-HSCT)的安全性和疗效.方法 接受allo-HSCT治疗的高龄(≥55岁)和(或)合并脏器功能损害的恶性血液病患者12例,其中急性髓系白血病6例,急性淋巴细胞自血病1例,慢性粒细胞白血病2例,骨髓增生异常综合征3例.预处理时,HLA相合供者移植的9例采用改良白消安-氟达拉滨(BuFlu)方案,其中Flu为50 mg/d,用5 d;行HLA不相合移植的2例采用改良BuFlu联合兔抗人胸腺细胞球蛋白(ATG)方案;行二次移植的1例采用全身放疗(TBI)-Flu方案.采用环孢素A、吗替麦考酚酯及短程甲氨蝶呤预防移植物抗宿主病(GVHD).结果 患者输注单个核细胞的中位数为6.68× 10~8/kg,输注CD34~+细胞的中位数为1.502 × 10~6/kg.allo-HSCT后所有患者均达到白细胞植入,植入时间中位数为17.5 d;除1例外,其余11例患者均达到血小板植入,植入时间中位数为14 d;HSCT后30 d,11例患者为完全供者型,仅1例为供受者嵌合状态.患者对预处理方案的耐受性良好,未发生严重预处理相关并发症.12例中,6例出现Ⅰ度以上急性GVHD,其中Ⅰ度2例,Ⅱ度3例,Ⅲ度1例;10例存活100 d以上的患者中,8例发生慢性GVHD;无GVHD相关死亡.随访62～554 d,10例无原发病复发存活,存活时间中位数为424 d,2例患者死亡,其中1例死于原发病未缓解,另1例死于移植后淋巴系统增殖性疾病.结论 高龄和(或)脏器功能损害的患者对应用Flu替代Cy的预处理方案的耐受性较好,且异体造血干细胞的植入顺利,原发病复发率未见明显升高.     

异基因造血干细胞移植后白血病髓外复发的临床分析

目的 探讨异基因造血干细胞移植(allo-HSCT)后髓外复发的发病机理、危险因素、治疗方法及临床转归.方法 回顾分析164例allo-HSCT受者的临床资料,选择受者性别、年龄、原发病、移植前疾病状态、是否有髓外浸润、预处理方案、供者类型、HLA相合程度、术后移植物抗宿主病(GVHD)发生情况等10个临床参数做单因素分析,对P＜0.1的单因素进行多因素分析.髓外复发的治疗方法包括局部放疗、单纯手术切除,全身化疗、供者淋巴细胞输注和二次移植.结果 164例受者均顺利重建造血功能.术后发生白血病髓外复发9例(5.5%),髓外复发的中位时间为7.5个月(2.3～42.6个月);术后发生急性GVHD 94例次(57.3%),慢性GVHD 83例次(50.6%).复发后有4例受者死亡.单因素分析表明,受者性别、移植前疾病进展期、移植前髓外浸润、供者类型及术后发生慢性GVHD等因素与白血病髓外复发显著相关(P＜0.1).经Cox回归多因素分析发现,移植前疾病处于进展期(P＜0.05)、白血病髓外浸润(P＜0.01)及术后发生慢性GVHD(P＜0.01)为alloHSCT后白血病髓外复发的独立危险因素.结论 多种因素参与了髓外复发的发病机理,免疫逃逸可能在其中起主要作用.疾病进展期、移植前伴髓外浸润和慢性GVHD是白血病髓外复发的独立危险因素.白血病髓外复发常伴随骨髓复发,预后较差,因此预防白血病细胞由髓外向髓内扩散对长期存活非常重要.     

达利珠单抗在未去T淋巴细胞单倍体相合的骨髓移植中的应用

目的探讨达利珠单抗预防未去T淋巴细胞单倍体相合骨髓移植后移植物抗宿主病(GVHD)的效果。方法9例白血病患者接受单倍体相合的骨髓移植，HLA有2～3个抗原错配，移植骨髓未去除T淋巴细胞，对受者除采取环孢素A、甲氨蝶呤、抗胸腺细胞球蛋白和霉酚酸酯联合应用等综合措施外，还分别在移植前2h和移植后第4d加用达利珠单抗预防GVHD。结果9例均获造血重建，骨髓植活直接证据证实为完全供者造血，无一例发生Ⅱ度以上急性GVHD，除1例因巨细胞病毒感染于移植后3个月死亡外，其余患者存活均超过1年，8例均发生局限性慢性GVHD，现无病存活者7例，1例在移植后14个月因原发病复发死亡。结论达利珠单抗联合其它免疫抑制措施对单倍体相合骨髓移植后的GVHD有较好的抑制作用。     

子-母微量嵌合体基础上同胞间非T淋巴细胞去除HLA半相合造血干细胞移植一例

目的为扩大供者来源,探讨在子-母微量嵌合体基础上同胞间非T淋巴细胞去除(Non-TCD)HLA半相合造血干细胞移植的可行性。方法受者的原发病为慢性粒细胞白血病(CML)急性淋巴细胞病变,供者为其胞弟,供、受者HLA有3个抗原不同,经套式序列特异引物聚合酶链反应技术检测,供者微量嵌合体阳性。采用全身照射、司莫司汀、阿糖胞苷、环磷酰胺及兔源抗胸腺细胞球蛋白等对受者进行预处理;采用环孢素A、霉酚酸酯及甲氨蝶呤预防移植物抗宿主病(GVHD)。结果移植后受者的外周血中性粒细胞>0.5×109/L和血小板>20×109/L的时间分别为11、18d,骨髓检查显示增生活跃,粒细胞系、红细胞系形态和比例正常;1、2、3、6个月和1年时完全供者型嵌合>90%。术后发生Ⅱ度急性GVHD及慢性局限性GVHD,经调整免疫抑制治疗方案后缓解。受者现基本恢复正常生活。结论子-母微嵌合体阳性的HLA半相合同胞可作为Non-TCD造血干细胞移植的供者。     

ABO血型主要不合异基因造血干细胞移植后纯红细胞再生障碍的临床分析

目的探讨ABO血型主要不合者异基因造血干细胞移植（allo-HSCT）后并发纯红细胞再生障碍（PRCA）的危险因素、临床转归以及PRCA的治疗和预防。方法42例行allo-HSCT，其中供、受者AN）血型主要不合者33例，主次双向不合者9例，27例受者血型为O型。预处理后，13例行骨髓移植，25例行外周血干细胞移植，4例行脐血移植。6例移植前行供者型血浆置换。移植后采用环孢素A（CsA）及短程甲氨蝶呤（MTX）联用预防移植物抗宿主病（GVHD）。结果42例均获得供者细胞植入，11例移植后并发PRCA（26．2％），11例的血型均为O型，其供者9例为A型，2例为B型；移植前行供者型血浆置换的O型受者，移植后均未发生PRCA。并发PRCA的11例中，8例经红细胞输注后自然缓解，2例行供者型血浆置换，其凝集素滴度下降后缓解，1例予利妥昔单抗治疗后缓解。单因素分析表明，O型受者、A型供者以及A型供给O型者与PRCA的发生相关，多因素分析表明，A型供给0型者是发生PRCA的独立危险因素（RR为10．999，95％可信区间为1．975-61．258，P〈0．05）。结论A型供给O型者与PRCA的发生密切相关；移植前行供者型血浆置换可预防PRCA的发生；供者型血浆置换和利妥昔单抗可有效治疗PRCA。     

不同动员方案对异基因造血干细胞移植临床疗效的影响

目的 探讨异基因造血干细胞移植中不同动员方案的临床效果.方法 回顾性分析71例异基因外周血造血干细胞移植的临床资料,根据供者采用动员剂的不同分为G-CSF动员组(G组,有24例受者)和G-CSF联合GM-CSF动员组(G+M组,有47例受者).比较两组供者的动员效果及移植物细胞成分,观察受者术后造血功能重建的情况和GVHD的发生情况,观察供者应用动员剂后的不良反应.结果 动员4 d后,G组供者的外周血白细胞计数为(49.6±19.5)×109/L,明显高于G+M组供者的(25.4±10.4)×109/L(P＜0.05).两组间CD34+细胞占单个核细胞比例的差异无统计学意义(P＞0.05),但G+M组CD34+CD38-细胞占CD34+细胞的比例为(37.7±5.7)%,明显高于G组的(31.4±4.5)%(P＜0.05).两组供者经过1～3次采集均能获取足够的CD34+细胞,两组采集的供者淋巴细胞计数及其亚群分布的差异均无统计学意义(P＞0.05).两组受者间CD34+细胞、CD34+CD38-细胞及T淋巴细胞亚群输入量的差异均无统计学意义(P＞0.05).术后所有受者的造血功能均顺利重建.术后对受者进行2～55个月的随访,无论是急性还是慢性GVHD,其发病率和严重程度在两组间的差异均无统计学意义(P＞0.05).术后共有17例受者死于原发病复发,10例死于GVHD和感染等移植相关并发症,G组和G+M组分别有14例(58.3%)和31例(66.0%)受者存活.在使用动员剂后,供者出现的主要不良反应为骨骼肌酸痛和发热,多发生在用药后36 h,给予解热镇痛药后缓解.结论 单用G-CSF与联合应用G-CSF和M-CSF进行动员的临床效果相当,但后者对CD34+CD38-细胞的选择性较强,而在异基因造血干细胞移植输入较多的CD34+细胞和CD34+CD38-细胞有利于受者造血功能的快速重建.     

非清髓性造血干细胞移植后并发移植物抗宿主病的相关因素分析

目的 探讨和分析非清髓性造血干细胞移植(NST)后并发移植物抗宿主病(GVHD)的相关因素.方法 选择34例血液病患者,其中重型再生障碍性贫血(SAA)15例,重型β-地中海贫血(TM)1例,肿瘤性血液病18例;进行无关供者脐带血造血干细胞移植(UCBT)11例,同胞供者骨髓联合外周血干细胞移植7例,外周血造血干细胞移植(PBSCT)16例.移植前采用以抗胸腺细胞球蛋白(ATG)、抗淋巴细胞球蛋白(ALG)或者氟达拉滨强效免疫抑制为基础的非清髓性预处理方案.GVHD的预防采用短程的甲氨蝶呤(MTX)联合环孢素A(CsA).观察非清髓性造血干细胞移植后的临床特点以及急、慢性移植物抗宿主病的发生情况;分析发生慢性移植物抗宿主病(cGVHD)的相关因素.结果 NST的植入率为91.2%.移植后7例肿瘤性血液病患者形成了供、受者造血细胞混合嵌合体(MC),给予供者淋巴细胞输注(DLI)2～9次后,例由MC转变为供者造血细胞完全嵌合体(FDC).随访12(3～96)个月,共发生Ⅰ～Ⅱ度急性移植物抗宿主病(aGVHD)5例,GVHD 15例.经统计学分析,发现年龄大的肿瘤性血液病患者经以ATG为基础的NST后,再给予DLI,其cGVHD的发生率高,且合并感染,对治疗的反应差;而以氟达拉滨为基础的NST患者发生cGVHD后治疗反应较好.移植100 d前后患者分别死亡3例和5例,其中3例死于广泛性cGVHD.结论 患者的年龄大、有合并症、以ATG为基础的预处理方案、肿瘤性血液病是NST后患者并发cGVHD的危险因素.     

非清髓性造血干细胞移植后移植物抗宿主病的临床观察

目的 观察非清髓性造血干细胞移植（NST）后移植物抗宿主病（GVHD）的发生情况。方法 将18例患者分为3组：A组为6例重型再生障碍性贫血（SAA）成人患者，行无关供者脐血造血干细胞移植；B组为5例SAA患者，行同胞供者骨髓联合外周血造血干细胞移植；C组为7例肿瘤性血液病患者，其中3例行同胞供者骨髓移植，4例行外周血造血干细胞移植。均采用以抗胸腺细胞球蛋白或抗淋巴细胞球蛋白为基础的预处理方案。A组和B组应用环孢素A（CsA）和甲泼尼龙预防GVHD，C组应用CsA和甲氨蝶呤预防GVHD。C组形成混合性嵌合体后行供者淋巴细胞输注（DLI）。结果 A组有4例形成并维持混合性嵌合体状态，1例死于真菌性败血症，1例自动出院。移植后早期，B组有3例供者型嵌合体占94％以上，并在短期内转变并维持完全供者嵌合体状态，获得无病存活，其中1例在移植后8个月发生慢性GVHD；另2例行供者千细胞输注后，1例6个月后死于继发性纵隔淋巴瘤，1例造血功能恢复。C组患者早期均形成混合性嵌合体，获得血液学部分缓解，患者DLI前无急性GVHD发生，1例于2次DLI后死于严重感染，1例失访；另5例分别经过4、3、7、5、4次DLI，全部转为完全供者型嵌合体，并获得血液学完全缓解，4例并发慢性GVHD，2例并发急性GVHD。结论 对于SAA患者，NST的临床效果较好，GVHD的发生率较低；而对于肿瘤性血液病，NST后患者的早期死亡率低，急性GVHD发生率下降，但慢性GVHD和感染的发生率较高。     

Medical research council trial of antilymphocyte globulin in renal transplantation. A multicenter randomized double-blind placebo controlled clinical investigation

A total of 173 patients who received live donor or cadaveric primary or secondary renal transplants at five British hospitals were entered into a randomized double-blind controlled clinical trial of equine antilymphocyte globulin (ALG) administered prophylactically to prevent rejection. The ALG was prepared in the early 1970s and used cultured human lymphoblasts as antigen. Following transplantation all patients were treated with a standard immunosuppressant regimen of steroids and azathioprine and, in addition, were given either 30 mg/kg ALG or placebo daily for 10 days by intravenous infusion. In comparison with more recently produced materials, the ALG employed in this study was of moderate potency in prolonging skin graft survival in monkeys. Primary graft failure occurred in 27 patients (15/86 ALG and 12/87 placebo). At three to five years after transplantation 50 of the remaining patients had died, almost all from diseases relating to their renal condition, and 25 more had suffered complete graft failure. No significant differences were found between patients treated with ALG and placebo in the numbers with functioning grafts during the 3 years following transplantation, in the time between transplantation and the first rejection episode, or in the number of episodes during the first six months after transplantation. This applied whether live or cadaveric grafts were employed. Within the first 6 months of operation, infection was given as a major contributory cause of death in 12 patients treated with ALG and in 5 who received placebo (P greater than 0.1). Infections were also slightly more common during the two weeks following transplantation in those receiving ALG (13/86 ALG, 10/87 placebo). As expected, graft survival was significantly better in patients who received live donor grafts (P = 0.001) and in patients with the least donor-recipient histocompatibility mismatches (P = 0.008). The results of this multicenter trial show no therapeutic benefit to renal graft recipients from the administration of ALG, and suggest that the risks of fatal infection may have been aggravated. Use of such equine ALG in similar dose regimens is therefore, not, justified in renal transplantation, especially if some part of the apparent effects on fatal infections is real. It is stressed that these findings are relevant only to the equine ALG used in this study, which was raised with cultured human lymphoblasts as the antigen, and to ALG prepared in a similar way and of similar potency. It should not be inferred that these results are applicable to ALG prepared in other ways.     

A phase I-II study evaluating the murine anti-IL-2 receptor antibody 2A3 for treatment of acute graft-versus-host disease

A murine IgG1 antibody specific for the IL-2-binding site on the human lymphocyte IL-2 receptor beta chain (CD25) was evaluated in 11 patients who developed acute graft-versus-host disease following allogeneic marrow transplantation. All patients had received cyclosporine and methotrexate for prophylaxis of GVHD, either alone (4 cases), or in combination with antithymocyte globulin (4 cases) or with prednisone (3 cases). Patients had developed GVHD at 7-53 days (median 12) after transplantation and had failed treatment with corticosteroids for 3-44 days (median 19). Residual GVHD was of grade II severity in 4 patients, grade III in 5 patients, and grade IV in 2 patients. Sequential patients received monoclonal antibody in escalating doses from 0.1 mg/kg/day to 1.0 mg/kg/day for 7 days. Side effects were fever, respiratory distress, hypertension, hypotension, and chills occurring in 11 of 72 (14%) antibody infusions. Trough antibody levels greater than 6 micrograms/ml were achieved in patients treated with 0.5 or 1.0 mg/kg/day. Four of eight evaluable patients had an IgM antibody response, and one had an IgG response to the murine immunoglobulin. Clinical response of GVHD was evaluated in 10 patients who received the entire course of the antibody treatment. Among 7 patients treated within 40 days from transplantation, one patient had a complete response in the skin as the only involved organ, and 3 patients had a partial response, 2 in the skin and one in the gastrointestinal tract. No responses were achieved with liver disease at anytime or in any organ in patients treated beyond 40 days after transplantation. Since administration of this antibody was well tolerated and some efficacy was observed in patients with acute GVHD treated early after transplantation, there is a rationale for testing this antibody as an agent for prophylaxis of GVHD.     

Improved efficacy of basiliximab over antilymphocyte globulin induction therapy in paediatric renal transplantation.

BACKGROUND: Basiliximab is a chimeric human/mouse monoclonal antibody directed against the alpha chain of the IL-2 receptor, CD25, which has been reported as successfully reducing rejection in adult renal transplant recipients. Reported clinical experience of basiliximab in paediatric renal transplantation is limited. METHODS: Using two intravenous doses on day 0 (pre-operatively) and day 4 with prednisolone and cyclosporin A (dual) maintenance immunosuppression in 42 children undergoing renal transplantation in our unit (SIM group), we have compared patient and graft outcome, rejection rates in the first 6 months, renal function and the incidence of Cytomegalovirus (CMV) infection with 42 consecutive children who previously received antilymphocyte globulin immunoprophylaxis with prednisolone, cyclosporin A and azathioprine (triple) maintenance immunosuppression (ALG group). The two groups were similar, including HLA mismatching, apart from age and size at transplantation (SIM=10.3+/-5.4 years vs ALG=12.4+/-4.2 years, P<0.05). RESULTS: One patient in the SIM group died from food inhalation with a functioning kidney and one patient in the ALG group from Pneumocystis pneumonia and post-transplant lymphoproliferative disorders with a rejecting graft. Both 1- and 2-year actuarial graft survivals were 93% for the SIM group and 86% for the ALG group (NS). Three grafts were lost in the SIM group-none from rejection (thrombosis 2, death 1)-and seven in the ALG group-three from rejection. Occurrence of biopsy documented rejection in the first 6 months after transplantation was 0.15+/-0.22 for the SIM group and 0.35+/-0.51 episodes per pt-month at risk for ALG treatment (P<0.04). Early rejection within 30 post-operative days occurred in only four SIM patients, three of whom had undergone retransplantation. Forty-seven per cent of rejection episodes occurred between days 30 and 44 in SIM treated patients. Switching to tacrolimus was similar in both groups; 24% of the SIM groups were prescribed triple therapy. Estimated glomerular filtration rate was 46.0 and 46.2 ml/min for SIM and ALG groups, respectively, six months after transplantation. Ten per cent of SIM and 19% of ALG treated patients developed clinically significant CMV infection (NS) but none of 16 (R(+)) SIM children had CMV infection compared with 8 out of 15 (R(+)) ALG patients (P<0.01). CONCLUSIONS: Basiliximab immunoprophylaxis and dual therapy reduces rejection episodes in the first six months and maintains graft survival and function after paediatric renal transplantation. Seventy-six per cent of children receiving basiliximab immunoprophylaxis were successfully maintained on long-term dual immunosuppression. This immunosuppressive protocol reduces CMV disease in CMV(+) recipients compared with ALG induction and triple therapy.     

Epstein-Barr virus associated lymphoproliferative diseases (B cell lymphoma) after transplantation

We report 12 cases of lymphomas which occurred among 1670 patients with kidney or combined renal and pancreatic transplantation. Group 1 comprised nine patients presenting with the diffuse form of the disease where immunoblasts or mature plasma cells massively infiltrated all organs. The first symptom was a viral syndrome, associated with a restriction of heterogeneity of immunoglobulins; oligoclonal to monoclonal peaks of immunoglobulins appeared about 50 days after transplantation. All patients received antilymphocyte globulins (ALG), and seven were treated with cyclosporin. EBV infection could be demonstrated in almost all patients; three EBV lymphoblastoid cell lines were established, their HLA phenotype being the same as the recipient of the graft. All patients finally died with renal and hepatic failure. Group 2 comprises three patients who presented solid B cell tumours of tonsils, lungs, and spleen at onset, extending to liver, kidney graft, lymph nodes, and brain. All received cyclosporin; two patients were treated with ALG, and one with OKT3. Immunoglobulins were polyclonal, oligoclonal, or decreased. Cell surface immunoglobulins were monoclonal on two tumours. EBV-DNA was positive within two tumours. Two patients presented EBV and CMV primary infection. CD4+T lymphocytes subsets were diminished at onset, and increased after cessation of immunosuppressive therapy. One patient died because of brain involvement; the two others are alive, one with perfect graft function. Therapy consisted of stopping immunosuppressive treatment, Acyclovir, and in two patients of group 2, monoclonal antibodies to pan-B and EBV receptor antigens.     

Haploidentical Stem Cell Transplantation for Acute Leukemia Patients Who Experienced Early Relapse Within One Year After the First Transplantation

To assess the safety and efficacy of allogeneic stem cell transplantation from haploidentical related donors (haplo-SCT) as 2nd transplantation for patients with early relapsed disease, we retrospectively evaluated 7 consecutive patients (median age, 42 years; range, 29–63 years) who experienced relapse within 1 year of the 1st transplantation and received haplo-SCT as a 2nd transplantation. Among the 7 patients who received haplo-SCT, 2 who were in morphologically complete remission (CR) at transplantation were conditioned with a reduced-intensity regimen, and the 5 non-CR patients were conditioned with a myeloablative regimen. Both conditioning regimens included antithymocyte globulin. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and methylprednisolone. Sustained neutrophil engraftment was achieved in all 7 patients. One patient developed severe acute GVHD. Notably, only 1 patient experienced relapse, and each patient achieved longer CR duration than after the 1st transplantation. Three of the 7 patients died from treatment-related causes: acute GVHD, post-transplantation lymphoproliferative disorder, and bacterial pneumonia. At the time of analysis, the 2-year overall survival rate of these 7 patients was 42.9%. This suggests that use of haploidentical related donors is a viable alternative for 2nd transplantation and should be confirmed in larger cohorts.     

异基因造血干细胞移植后早期深部真菌感染风险因素分析

目的提高对异基因造血干细胞移植后早期深部真菌感染风险的认识。方法分析22例异基因造血干细胞移植患者的移植方式、病程、白细胞植入时间、移植后白细胞计数与早期深部真菌感染的相关性。结果6例患者异基因造血干细胞移植后早期发生深部真菌感染。采用半相合和无关供者的造血干细胞移植的患者深部真菌感染发生率明显高于全相合亲缘供者的造血干细胞移植,使用过兔抗人胸腺淋巴细胞球蛋白(ATG)或猪抗人淋巴细胞球蛋白(ALG)的患者,深部真菌感染发生率明显高于未使用者。在全相合的亲缘供者的造血干细胞移植中,真菌感染与非感染患者移植后0和14d白细胞计数存在显著性差异,而两组患者移植前病程和移植后7、21 d的白细胞计数差异无显著性。结论移植方式、使用ATG或ALG、移植后0和14 d白细胞数是移植后早期深部真菌感染发生的危险因素。     

肝移植术后巨细胞病毒感染(附31例临床分析)

目的 探讨肝移植术后巨细胞病毒感染的诊断和防治。方法 回顾分析１９９３年４月至１９９９年６月我科所进行的３１例肝移植病人临床资料,并结合文献进行讨论。结果 共有５例病人发生活动巨细胞病毒感染,发生率为１６．１％,其中１例发生巨细胞病毒性肺炎,其余４例为无临床症状的活动性巨细胞病毒感染。４例治愈,１例死亡。与巨细胞病毒感染相关的病死率为３．２％。结论 外周血巨细胞病毒抗原血症测试是诊断巨细胞病毒感染     

强化预处理allo-HSCT联合伊马替尼治疗费城染色体阳性ALL八例

目的 总结强化预处理异基因造血干细胞移植(allo-HSCT)联合伊马替尼治疗费城染色体阳性(Ph+)急性淋巴细胞白血病(ALL)的经验.方法 接受同胞allo-HSCT的Ph+ALL患者8例,移植前均达完全缓解(CR),其中5例在移植前后使用伊马替尼,3例未使用.8例中,7例采用以白消安+环磷酰胺(BuCy2)为基础的增强预处理方案,1例采用全身放疗(TBI)+Cy的增强预处理方案.患者输注单个核细胞的中位数为6.02×108/kg,输注的CD34+细胞的中位数为3.14×106/kg.术后采用环孢素A(CsA)及甲氨蝶呤(MTX)预防移植物抗宿主病(GVHD).结果 allo-HSCT后所有患者均达到白细胞植入和血小板植入,白细胞植入时间中位数为15.5 d,血小板植入时间中位数为19d;allo-HSCT后30 d,8例患者经检测均为完全供者型.患者对预处理方案的耐受性良好,未发生严重预处理相关并发症.8例患者中,4例患者发生急性GVHD,其中Ⅰ度2例,Ⅱ度1例,Ⅳ度1例.7例存活100 d以上的患者中,3例发生慢性GVHD.随访结束时共6例患者存活,其中3例无白血病存活,3例复发.死亡2例,1例死于原发病复发,1例死于急性GVHD.结论 强化预处理allo-HSCT联合伊马替尼是治疗Ph+ALL的有效方法,但在应用过程中应注意伊马替尼的抗慢性GVHD作用.

Abstract：

Objective To evaluate the outcome of combination of intensive preconditioning regimen allo-HSCT with imatinib for treatment of Ph chromosome positive acute lymphocyte leukemia (ALL). Methods Between 2009 and 2010, 8 patients diagnosed as Ph+ ALL received allo-HSCT from HLA identical sibling during complete remission. Imatinib was added into the therapies of 5 patients.Seven patients received the intensive preconditioning regimen based on BuCy2, one patient received the regimen of TBI-Cy. A median of 6. 02 × 108/kg mononuclear cells and 3. 14 × 106/kg CD34+ cells were transfused. GVHD prophylaxis included cyclosporine A and methotrexate. Results All patients were well tolerant to the regimen without serious regimen-related toxicity. The median time of ANC≥0. 5 × 109/L was 15. 5 days, and that of PLT≥20 × 109/L was 19 days. Thirty days after allo-HSCT, all patients got donor engraftment successfully. Among 8 cases, 4 cases presented acute GVHD, 2 developed degree Ⅰ , one developed degree Ⅱ , and one developed degree Ⅳ. Seven patients were alive 100 days after allo-HSCT, 3 of whom presented chronic GVHD. At the end of following-up period, 6 patients were alive, among them, 3 patients were alive without relapse; 3 patients relapsed; Two patients died, one from acute GVHD, and one from leukemia relapse. Conclusion Combined intensive preconditioning regimen allo-HSCT with Imatinib was an effective treatment for Ph+ ALL, but the effect of anti-chronic GVHD of imatinib should arouse certain attention.