单倍型异基因造血干细胞移植治疗儿童难治性或复发白血病30例

目的 探讨单倍型异基因造血干细胞移植(allo-HSCT)治疗儿童难治性或复发白血病的疗效和安全性.方法 2007年6月至2011年6月间难治性或复发白血病患儿30例接受亲缘单倍型相合allo-HSCT.患儿的原发病为急性髓系白血病(AML) 14例,急性淋巴细胞白血病(ALL) 16例.30例中,首次复发11例,2次或以上复发16例,原发难治性3例.获取供者骨髓+外周血干细胞用于移植.预处理药物采用阿糖胞苷、白消安(Bu)、氟达拉滨及全身照射等.联合使用环孢素A(CsA)+短程甲氨蝶呤(MTX)+吗替麦考酚酯(MMF)+抗人胸腺细胞球蛋白(ATG)等预防移植物抗宿生病(GVHD).结果 30例均获造血重建,中性粒细胞≥0.5×109/L及血小板≥20×109/L的平均时间分别为18.5d及24.2 d,均为完全供者植入.患儿随访时间中位数为22.5个月,随访期间共12例发生急性GVHD,6例发生慢性GVHD.因GVHD死亡4例,感染死亡3例,复发死亡6例,其余1 7例患儿仍无病存活,2年无病存活率为55％.结论 单倍型allo-HSCT治疗儿童难治性或复发白血病安全、可行.     

供者型CIK细胞输注治疗异基因造血干细胞移植后白血病复发

目的 采用受者体内供者型或供者来源的细胞因子诱导杀伤细胞(CIK细胞)过继性免疫治疗异基因造血干细胞移植(allo-HSCT)后白血病复发的效果.方法 回顾性分析2例allo-HSCT后白血病复发患者输注供者型CIK细胞成功开展过继性免疫治疗的临床资料.例1在移植后986 d出现白血病复发,经化疗取得短暂部分缓解,采集受者外周血完全供者型单个核细胞扩增CIK细胞,先后给予受者5个周期的CIK细胞治疗.例2在亲缘allo-HSCT后158 d出现白血病复发,采集亲缘供者外周血单个核细胞扩增CIK细胞,于移植后204 d和294 d给予2个周期的CIK细胞输注治疗.结果 例1经化疗降低白血病细胞负荷后,经过1个周期的CIK细胞输注治疗,获得完全缓解,之后再次给予4个周期CIK细胞治疗,随访7个月取得持续完全缓解.例2复发后停用免疫抑制剂,并行化疗及输注供者干细胞采集物,于移植后187 d出现急性移植物抗宿主病及髓外浸润情况,移植后204 d输注1个周期的CIK细胞后,症状明显减轻.移植后294 d给予第2个周期的CIK细胞治疗,骨痛缓解,现骨髓细胞学持续完全缓解,髓外病灶消失.结论 受者体内供者型或供者来源的CIK细胞可用于allo-HSCT后白血病复发的治疗,效果良好,耐受性好.     

非亲缘脐血造血干细胞移植治疗儿童非霍奇金淋巴瘤1例报道

目的观察非亲缘异基因脐血造血干细胞移植治疗儿童非霍奇金淋巴瘤的临床效果。方法 1例5岁非霍奇金淋巴瘤（Ⅳ期）患儿接受了高剂量放化疗联合非亲缘异基因脐血造血干细胞移植的治疗。结果静脉输注脐血后无异常反应。白细胞植入时间为移植后17d,血小板植入时间为移植后25d。移植后出现Ⅰ度急性移植物抗宿主病（GVHD）,分别于24d、40d采集患者外周血,经短串联重复序列GeneScan方法分析判定供者造血干细胞在患者体内存活。患儿移植后43d出院,随访至2010年6月,已无病存活67个月,至今状况良好,无复发、无并发症、无慢性GVHD发生。结论大剂量化疗联合非亲缘异基因脐血造血干细胞移植治疗非霍奇金淋巴瘤儿童患者的移植效果较好,并发症较少。     

3例造血干细胞移植术后并发重度肠道移植物抗宿主病患者的护理

对2例慢性髓性白血病和1例急性髓性白血病患者行异因因造血干细胞移植(allo-HSCT).干细胞分别来自血缘HLA相合、非血缘HLA相合及血缘HLA 1个位点不合的供者.3例患者于移植后60、105、116 d并发重度肠道移植物抗宿主病(GVHD),予以免疫抑制剂治疗及相应的护理措施,结果1例因肺部结核杆菌及白色念珠菌感染死亡,2例得到有效控制.提示allo-HSCT后并发重度肠道GVHD进展快、症状重,密切观察病情,加强消化道护理、心理护理、保护性隔离及用药护理对移植患者的预后至关重要.     

单倍体造血干细胞移植治疗急性淋巴细胞白血病植入失败的二次移植策略

目的探讨急性T淋巴细胞白血病患者初次单倍体造血干细胞移植后植入失败并发生致命性并发症的二次移植策略。方法 1例男性患者诊断为急性T淋巴细胞白血病,2015年11月接受供者为其胞妹的首次单倍体造血干细胞移植后植入失败,并发生大肠杆菌败血症、血清病、肝静脉闭塞症和多器官功能衰竭。首次移植后32 d行供者为其父亲的挽救性二次单倍体造血干细胞移植,二次移植前未进行预处理化学药物治疗(化疗),采用移植后环磷酰胺(PTCy)方案为基础的移植物抗宿主病(GVHD)预防方案。结果造血干细胞移植术后12 d白细胞植入,术后67 d血小板植入。血清病、败血症及肝静脉闭塞症治愈,器官功能改善。但移植后第18个月,即2017年6月,患者死于白血病复发。结论植入失败患者二次移植前不进行预处理化疗,采用PTCy预防GVHD有望获得成功植入。     

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.     

3例造血干细胞移植术后并发重度肠道移植物抗宿主病患者的护理

对2例慢性髓性白血病和1例急性髓性白血病患者行异因因造血干细胞移植（allo-HSCT）。干细胞分别来自血缘HLA相合、非血缘HLA相合及血缘HLA1个位点不合的供者。3例患者于移植后60、105、116d并发重度肠道移植物抗宿主病（GVHD），予以免疫抑制剂治疗及相应的护理措施，结果1例因肺部结核杆菌及白色念珠菌感染死亡．2例得到有效控制。提示allo-HSCT后并发重度肠道GVHD进展快、症状重，密切观察病情。加强消化道护理、心理护理、保护性隔离及用药护理对移植患者的预后至关重要。     

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.     

减低强度预处理异基因造血干细胞移植治疗高危骨髓增生异常综合征的效果

目的 探讨减低强度预处理异基因造血干细胞移植(allo-HSCT)治疗高危骨髓增生异常综合征(MDS)的疗效和安全性.方法 应用减低强度预处理allo-HSCT治疗2012年1月至2014年1月我科收治的10例高危骨髓增生异常综合征患者,其中男6例,女4例,平均年龄30.3岁,确诊至移植的中位时间为4.5个月,7例为HLA配型全相合,3例为HLA配型不合,供者接受粒细胞集落刺激因子动员,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氟达拉滨(FLU)、环磷酰胺(CTX)及抗人淋巴细胞免疫球蛋白(ATG),移植物抗宿主病(GVHD)预防采用联合免疫抑制剂(包括环孢素A、氨甲蝶呤等).移植后观察全部患者毒副反应、GVHD和无病生存等情况.结果 全组患者均获造血重建,中性粒细胞≥0.5×109/L及血小板≥20×109/L的平均时间分别为分别19.7d及23.8d,植入证据检测为100％完全供者造血.随访至2014年10月,中位随访时间20.5个月(8～32个月).2例患者死于复发,并发症死亡1例,其他患者目前仍处于完全缓解状态,无病生存率达到70％,最长无病生存时间已达32个月.结论 Allo-HSCT是治疗高危MDS的可行方法,疗效好、安全系数大,可在临床广泛开展.     

亲缘异基因造血干细胞移植治疗慢性髓细胞白血病的护理

对30例慢性髓细胞白血病患者行亲缘异基因造血干细胞移植.27例患者预处理采用经典或改良BuCy2方案,3例患者用非清髓方案;预防移植物抗宿主病(GVHD)采用短程甲氨蝶呤联合环孢素A方案;在常规护理的基础上针对感染、GVHD及心理问题实施重点护理.结果 所有患者均获造血功能重建;移植后100 d内发生Ⅱ～Ⅳ度急性GVHD 7例(23.3%),经对症处理好转出院.随访3～88个月,移植相关死亡7例,疾病复发死亡1例,22例移植成功.提出移植相关并发症及移植后感染的护理是保证疗效的关键.     

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.     

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.     

伊马替尼联合供者淋巴细胞输注治疗造血干细胞移植后慢性粒细胞白血病复发

目的 探讨伊马替尼联合供者淋巴细胞输注(DLI)治疗异基因造血干细胞移植后慢性粒细胞白血病(CML)复发的效果.方法 3例CML(慢性期)患者,在接受预处理后,例1接受其胞妹外周血造血干细胞移植,例2接受其胞兄的骨髓移植,例3接受其胞弟的骨髓与外周血造血干细胞联合移植.例1移植后采用环孢素A(CsA)和霉酚酸酯(MMF)预防移植物抗宿主病(GVHD),例2采用CsA、短程甲氨蝶呤(MTX)、抗胸腺细胞球蛋白及抗CD25单克隆抗体预防GVHD,例3应用CsA、MTX和MMF预防GVHD.采用细胞遗传学及荧光原位杂交技术动态监测治疗效果.移植后发生血液学复发时,给予伊马替尼口服,并行DLI.结果 例1移植后30 d行DLI,输注CD3+T淋巴细胞0.5×107 /kg,移植后50 d和70 d,再次行DLI,分别输注CD3+ T淋巴细胞1.0 × 107 /kg和2.0×107 /kg,短串联重复序列(STR)检测提示为完全供者嵌合(DC).移植后120 d,疾病进展,给予伊马替尼400 mg/d,同时输注供者CD3+ T淋巴细胞2.5 × 107/kg.移植后180 d,STR检查提示仍为DC.患者最终于移植后17个月因髓外复发死亡.例2的染色体核型于移植后35 d转变为46,XY,XY为100%,BCR-ABL融合基因阴性.移植后100 d,原发病复发.停用免疫抑制剂,输入供者CD3+ T淋巴细胞3.9×107 /kg,同时口服伊马替尼500 mg/d.DLI联合伊马替尼治疗后30 d,患者的染色体核型为46,XY,XY为100%,BCR-ABL融合基因阴性,患者至今无病存活53个月.例3移植后5 d造血功能获得重建,移植后60 d,染色体核型为46,XY.移植后120 d,确诊CML复发,遂给予伊马替尼400 mg/d,并行DLI,共输注供者CD3+ T淋巴细胞8×107 /kg,1个月后,患者的染色体核型再次转为46,XY,患者至今无病存活50个月.结论 伊马替尼联合DLI对造血干细胞移植后CML复发具有一定的治疗效果.     

A prospective analysis of immune recovery in children following allogeneic transplantation of t-cell-depleted or non-T-cell-depleted hematopoietic cells from HLA-disparate family donors

Transplantation of HLA-disparate hematopoietic stem cells from related donors is an alternative for the treatment of patients lacking an HLA-matched family or unrelated donor. In the cases of a single HLA antigen disparity, extensive T-cell depletion (TCD) is not required, yet antithymocyte globulin (ATG) must be administered to prevent GvHD or graft rejection. The major concern after HLA-mismatched transplants remains immune reconstitution. Therefore, we prospectively studied the recovery of lymphocyte subsets among 22 children transplanted from partially HLA-matched family donors. We compared two groups of patients: (1) the TCD group included children (n = 1.3) who received grafts after TCD (MACS) due to an HLA disparity for more than one antigen; (2) The non-TCD group included children with either one HLA-mismatched antigen, n = 7; or more than one disparate antigen (n = 2) who received T-cell-repleted grafts and ATG. The study demonstrated rapid NK cell reconstitution among the TCD group. TCD compromised T-cell reconstitution, thus preventing GvHD, but resulting in a higher incidence of severe infectious complications, graft rejection, and disease relapse. Increasing mixed chimerism required the application of donor T-cell addbacks, thus potentiating the risk of GvHD. Primary graft rejection occurred in eight children, who required further transplants. In the non-TCD group faster T-cell reconstitution (predominantly CD3+CD8+ cells) resulted in a lower rate of relapse and infection, yet a higher rate of GvHD, including two fatal cases. Due to improved immune reconstitution, in spite of an increased risk of GvHD, non-TCD transplants from single HLA-mismatched family donors remain a valuable option for children without matched donors.     

HSCT联合伊马替尼治疗费城染色体阳性急性淋巴细胞白血病

目的 观察造血干细胞移植(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)患者的疗效,分析影响预后的因素.方法 Ph+ALL患者32例,全部患者移植前均达血液学完全缓解,其中第1次缓解(CR1)期27例,CR2期5例.19例患者移植前达到分子生物学缓解(MR).32例中,自体移植4例,异基因移植28例.采用全身照射(TBI)+环磷酰胺(Cy)+氟达拉滨(Flu)+阿糖胞苷(Ara-C)的预处理方案.患者输注单个核细胞的中位数为5.6×108/kg,输注CD34+细胞中位数为2.94×106/kg.31例患者于HSCT前应用伊马替尼,口服,400～600 mg/d;16例患者于HSCT后应用伊马替尼,包括预防性治疗7例,剂量为300～400mg/d,治疗9例,剂量为400～600 mg/d.结果 32例患者移植后均获得造血重建.全部患者预期3年总体存活率为(62.1±8.6)%,无白血病存活率为(59.2±8.7)%,复发率为(17.7±7.2)%,移植相关死亡率为(26.2±8.0)%.4例自体移植患者均存活,其中3例已持续缓解14、18和67个月.对异基因移植进行单因素分析显示,行HLA匹配亲缘HSCT者的总体存活率为76.5%,高于行无关供者或HLA半相合亲缘HSCT者(27.3%,P＜0.05),前者无白血病存活率也高于后者(分别为70.6%和27.3%,P＜0.05).移植前获得MR者的复发率为5.6%,低于未缓解者(40.0%,P＜0.05),移植前处于CR1期者的复发率为12.5%,低于CR2期者(50.0%,P＜0.05).结论 伊马替尼联合HSCT可用于治疗Ph+ALL患者,移植前获得MR或于CR1期进行移植者的预后更佳.

Abstract：

Objective To analyze the outcomes and the prognostic factors of hematopoietic stem cell transplantation (HSCT) in combination with imatinib for Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Methods All 32 patients with Ph+ ALL achieved hematologic complete remission (CR) at time of transplantation, including 27 cases in the first CR (CR1) and 5 in CR2. Nineteen patients achieved molecular remission (MR). Among 32 patients, 4 received autologous HSCT (AHSCT), and 28 allogeneic HSCT (allo-HSCT). The conditioning regimens comprised of total body irradiation (TBI), cyclophosphamide, fludarabine and cytarabine. The median number of transfused mononuclear cells was 5. 6 × 108/kg, and that of CD34+ cells was 2. 94 × 106 /kg. Thirty-one patients were administrated imatinib orally before transplantion, at a dose of 400～600 mg/day, and 16 patients after transplantation, including 7 for prevention at a dose of 300～400 mg/day and 9 for salvage treatment at a dose of 400 ～ 600 mg/day. Results Hematopoietic reconstitution was achieved in all 32 patients. Three-year estimate of overall survival (OS) was (62. 1±8. 6)%, leukemia-free survival (LFS) (59. 2 ± 8. 7)%, relapse rate (RR) (17. 7 ± 7. 2)% and transplant-related mortality (26. 2 ± 8. 0) %. All 4 undergoing AHSCT were alive, and 3 out of them were in continuous CR with durations of 14, 18 and 67 months respectively. The univariate analysis for prognosis in allo-HSCT showed that the OS of HLA-matched sibling donors group was 76. 5 %,higher than that of unrelated or haploidentical donors group (27. 3 %, P＜0. 05), and so was LFS (70. 6 % vs 27. 3 %, P＜0. 05). RR in patients achieving MR at time of transplantation was 5. 6 %,lower than that in those not achieving MR (40. 0 %, P＜0. 05). RR in patients in CR1 at time of transplantation was 12. 5 %, lower than that in those in CR2 (50 %, P ＜0. 05). Conclusion Imatinib improved the outcomes of HSCT for Ph+ ALL, especially to patients achieving MR at time of transplantation and transplantation in early stage (CR1).     

Long-term follow-up of peripheral blood stem cell transplantation from mismatched related and unrelated donors

Allogeneic stem cell transplantation (SCT) is best performed with an HLA-identical sibling donor (matched related donor, MRD) to reduce the risk of early complications such as acute graft-vs.-host disease (aGvHD). However, as only about 30% of recipients have an MRD for this potentially curative approach, the use of family donors with one or two mismatches in the HLA-antigens (mismatch related donor, MMRD) or fully matched unrelated donors (MUD) ('alternative donors') has been introduced in the allogeneic SCT setting in recent years. To evaluate the feasibility of allogeneic SCT from alternative donors by using peripheral blood stem cells (PBSC) we initiated a prospective, phase II study in 1996. From April 1996 to July 1998, 18 patients with various hematological malignancies underwent allogeneic SCT from alternative donors (two patients with MUD and 16 patients with MMRD). All patients received stable engraftment and none of the patients had graft rejection. The rate of aGvHD (grades II-IV) and the relapse rate at last follow-up (seven to nine yr after SCT) were with 40% and 24%, respectively, comparable with those found in patients receiving allogeneic SCT from MRD. However, five yr after allogeneic SCT only 17% were alive, which was mainly due to the treatment-related mortality (TRM) rate of 59%. We conclude that allogeneic PBSC transplantation by using alternative donors is associated with an unsatisfying long-term TRM rate. The significance of TRM and particular late deaths has to be evaluated further in this transplantation setting.     

非清髓性外周血干细胞移植后白血病复发的防治

目的探讨非清髓性造血干细胞移植后白血病复发的防治。方法7例合并有其它系统疾病的白血病患者接受非清髓性外周血干细胞移植,移植后采用环孢素A及短程甲氨蝶呤预防移植物抗宿主病(GVHD),造血细胞植入后,动态检测骨髓单个核细胞嵌合体的变化,根据嵌合体状态,采用供者淋巴细胞输注(DLI),并配合环孢素A用量的调整来防治白血病复发。结果7例患者移植后造血功能得到恢复,3例移植前合并的疾病有所加重,经处理缓解,移植早期相关并发症少而轻。移植后有3例嵌合体由混合嵌合体(MC)转为完全供者型嵌合体(CC),再转为MC,伴Ph染色体阳性,DLI5~6次后Ph染色体转为阴性,嵌合体状态又转为CC,其中2例发生广泛皮肤慢性GVHD;3例的嵌合体持续为CC,无复发,其中2例接受了1次DLI,此2例在环孢素A减量过程中发生GVHD;1例的嵌合体持续为MC,虽经3次DLI,但无效,患者死于白血病复发。结论非清髓性造血干细胞移植后应动态监测嵌合体状态,采用供者淋巴细胞输注,并配合环孢素A用量的调整,对白血病的复发有一定的效果。     

Induction of immune alterations and successful renal transplantation with a simplified method of donor-specific blood transfusion

We developed a new and simplified donor-specific blood transfusion (DSBT) protocol for prospective kidney transplant recipients from one-haplotype-mismatched related donors. Prospective kidney donors gave 450 ml of blood in a quad-pack unit, and the blood was stored in a blood bank. Twenty-five patients were transfused with 100 ml of the respective donor's whole blood at 1, 8, and 15 days after its storage. After DSBT, only three (12%) developed donor-specific lymphocytotoxic antibodies. Following DSBT, donor-specific mixed lymphocyte culture (MLC) was significantly suppressed, without any accelerated (secondary-type) response in early MLC. In addition, sera obtained after DSBT also suppressed donor-specific MLC significantly. Sixteen recipients subsequently received a kidney transplant from the donor, and all had functioning grafts at three months, but one lost the graft thereafter (graft survival rate: 94% at 12 months). This study indicates that (1) 100 ml of stored whole-blood DSBT three times at weekly intervals is a practical, less immunizing, and effective approach to enhance graft survival in recipients of a one-haplotype-mismatched graft; and (2) immune consequences of DSBT include induction of donor-specific cellular and humoral adaptive responses that might be conducive to successful graft outcome.     

Azacitidine for Relapse After Allogeneic Stem Cell Transplantation—Single-Center Study

Background

Relapse is the leading cause of treatment failure for myeloid malignancies treated with allogeneic hematopoietic stem cell transplantation. Treatment options are very limited and use of azacitidine is one of the available options.