异基因骨髓移植的国内外现状和展望

异基因骨髓移植的国内外现状和展望陆道培，郭乃榄中国的骨髓移植登记组为隶属于中华医学会器官移植学会与血液学会的一个学术团体，象国际骨髓移植登记组（ＩＢＭＴＲ）一样，它的登记病例为同基因骨髓移植（Ｓｙｎ－ＢＭＴ）与异基因骨髓移植（Ａｌｌｏ－ＢＭＴ）。自中...     

亲缘异基因骨髓移植供者的护理

20 0 0年 7月至 2 0 0 1年 7月 ,我科对 10例白血病病人行亲缘异基因骨髓移植术 (Ａｌｌｏｇｅｎｅｉｃｂｏｎｅｍａｒｒｏｗｔｒａｎｓｐｌａｎｔａｔｉｏｎ ,Ａｌｌｏ ＢＭＴ) ,治疗效果理想。现将移植供者的护理报告如下。1　临床资料一般资料 :10例供者中 ,男 8例、女 2例 ,年龄2 2～ 4 6岁 ,中位年龄 36岁。小学文化程度 1例 ,初中 3例 ,高中 6例 ;其中已婚 9例 ,未婚 1例。供髓前健康体检 (包括心、肺、肝、肾功能检查及常规病毒学检查 )均无异常。方法 :供者骨髓的采集在受者预处理结束后 ,输注骨髓的当日在手术室无菌条件下完成。采…     

异基因骨髓移植后白血病复发的过继性免疫治疗

观察异基因骨髓移植（Ａｌｌｏ－ＢＭＴ）后白血病复的患者共６例。其中遗传学复发与脑膜白血病复发各２例；骨髓复发与髓外浸润各１例。复发后先进行全身或中化疗，之后输注取自同一供者，用ＣＳ３０００血细胞分离机分离的白细胞，有核细胞总数（０．６８－１４．７６）×１０＾８／ｋｇ，此后不再进行局部或全身化疗。结果４例诱发出不同和蔼的移植物抗宿主病（ＧＶＨＤ），随之病情得以控制，但１例死于间质性肺炎。其余２例虽未     

小儿异基因骨髓移植六例报告

对４例重症β地中海贫血患儿及２例重症再生障碍性贫血患儿进行异基因骨髓移植，患者年龄１１个月至１０岁。供受者ＨＬＡ全相合１例，亲子之间半相合或１个位点不相合５例。３例术后查得植活证据，持久性植活，１例长期无病生存。对影响植入的因素，如ＨＬＡ匹配程度、预处理方案、移植物抗宿主病及感染的防治措施及小儿骨髓移植中的一些问题进行了讨论。     

异基因骨髓移植174例报告

异基因骨髓移植１７４例报告北京医科大学人民医院血液病研究所（１０００４４）郭乃榄，陆道培，郑缓，范蕴明，黄晓军，张耀臣，卢锡京，史琪，吴彤，许兰萍，邓星明，陈欢异基因骨髓移植（Ａｌｌｏ－ＢＭＴ）在医学中的地位已被公认，但某些严重合并症如移植物抗宿主病...     

齐墩果酸对小鼠异基因骨髓移植免疫重建的影响

用去ＴＸ划基因骨髓成功地重建了致死量照射小鼠的免疫功能，但移植后受体免疫功能恢复缓慢。给齐墩果酸（ＯＬＡ）后，受体鼠淋巴细胞增殖反应及空斑形成细胞（ＰＦＣ）反应增强，明显促进白细胞介素２的产生，迟生性超敏反应（ＤＴＨ）也有增加趋势，受体鼠脾细胞培养上清游人液有明显的非特异性免疫抑制作用，去Ｔ细胞后抑制作用消失，给ＯＬＡ后，这一抑制作用有减弱的趋势。     

HLA不相合异基因骨髓移植后早期造血功能障碍一例

我们曾遇到 1例接受异基因骨髓移植 (ａｌｌｏ ＢＭＴ)的慢性粒细胞性白血病患者在移植物植活、造血功能重建后早期出现造血功能障碍 ,经加大环孢素Ａ(ＣｓＡ)的用量 ,并联合应用糖皮质激素和粒细胞刺激因子 (Ｇ ＣＳＦ)治愈 ,随访至今已 2年 ,患者带慢性局限型移植物抗宿主病 (ＧＶＨＤ)存活 ,现将本例报道如下。一、病例报告1.一般资料 :患者为男性 ,2 0岁 ,1997年 12月确诊为慢性粒细胞性白血病 (ＣＭＬ)慢性期。经用羟基脲治疗 2个月 ,ＭＡ(米托恩醌 ,阿糖胞苷 )及ＨＯＡＰ(三尖杉酯碱 ,长春新碱 ,阿糖胞苷 ,泼尼松 )方案一疗程 ,血象及…     

异基因骨髓移植后合并感染30例临床分析

目的：分析异基因骨髓移植（allo-BMT）后感染的发生情况.方法：回顾性分析2008年6月-2009年6月30例allo-BMT患者的临床资料.患者均经过移植前预处理、移植物抗宿主病（GVHD）和感染的预防性治疗.移植后感染患者经验性给予抗细菌、抗真菌、抗病毒及抗结核治疗.结果：30例患者发生感染并发症33例次.由一种病原菌引起的感染21例次,其中细菌性感染10例次,间质性肺炎2例次,真菌感染5例次,肺结核1例次,带状疱疹3例次;≥2种病原所致的感染并发症12例次.患者均伴有不同程度的GVHD.3例GVHDⅢ～Ⅳ级患者因肺部混合感染导致死亡,其余治疗后好转.结论：混合感染仍是骨髓移植最常见的并发症,并与GVHD的发生相关.     

内皮祖细胞抑制小鼠异基因骨髓移植后肝小静脉血栓形成的作用

目的 探讨内皮祖细胞(EPC)抑制异基因骨髓移植后肝小静脉血栓形成的作用.方法 采用随机数字表法将Balb/c小鼠分为3组,单纯骨髓移植组的小鼠在全身照射后经尾静脉输注C57BL/6小鼠的骨髓单个核细胞5×106/只 ;联合EPC移植组则在单纯骨髓移植的基础上同时输注C57BL/6小鼠的EPC 5×105/只 ;正常对照组的小鼠不作任何处理.分别于移植后第0、5、10、15和20天时,计算各组小鼠的肝脏指数,光镜下观察肝小静脉血栓形成情况以及肝细胞及血管内皮损伤情况,电镜下观察肝小静脉、肝血窦内皮、肝细胞损伤及血小板黏附情况,检测外周血活化血小板的比例及肿瘤坏死因子α(TNF-α)浓度的变化.结果 移植后第0、5、10、15和20天时,单纯骨髓移植和联合EPC移植组的活化血小板比例、肝脏指数和外周血TNF-α浓度均呈现上升趋势,至第15天时达到高峰,随后下降,但仍明显高于正常对照组(P＜0.05) ;各时间点联合EPC移植组的上述指标均明显低于单纯骨髓移植组,差异均有统计学意义(P＜0.05).与单纯骨髓移植组比较,联合EPC移植组的血小板黏附减少,肝小静脉血栓形成较少,肝细胞水肿和坏死程度均较轻,且肝脏损伤修复较快.结论 小鼠骨髓移植时联合输注EPC能显著抑制肝小静脉血栓形成,明显减轻肝脏损伤.     

Bronchiolitis obliterans organizing pneumonia (BOOP) with suspected liver graft-versus-host disease after allogeneic bone marrow transplantation

We report on a patient with chronic myelogenous leukemia who developed bronchiolitis obliterans organizing pneumonia (BOOP) after allogeneic bone marrow transplantation (BMT). A 19-year-old Japanese male complained of dry cough and dyspnea 7 months after BMT. The chest X-ray and computed tomography revealed patchy infiltrates bilaterally. Lung function test, lung biopsy and bronchoalveolar lavage were consistent with the diagnosis of BOOP. The patient also suffered from suspected graft-versus-host disease (GVHD) of the liver, after discontinuation of cyclosporine. Furthermore, prednisolone proved effective against the BOOP and the liver dysfunction. These findings indicate that BOOP is a possible pulmonary manifestation of chronic GVHD, and that immunological mechanisms may have effected the onset of BOOP after BMT in this case. Received: 18 May 2000 Revised: 30 October 2000 Accepted: 23 May 2001     

Induction of transplantation tolerance by intraportal injection of allogeneic bone marrow cells: Possible implications for intrauterine bone marrow transplantation across major histocompatibility barriers

Abstract. Intraportal inoculation of C57BL/6 marrow cells into sublethally (400 rad) irradiated BALB/c recipients resulted in durable chimerism and the permanent acceptance of C57BL/6 skin allografts. Sublethally irradiated recipients of a similar number of marrow cells inoculated systemically did not develop chimerism or any significant prolongation of the survival of C57BL/6 skin allografts. Consequently, lethal graft-versus-host disease developed only in recipients of intraportal marrow allografts (80%). The intraportal injection of allogeneic C57BL/6 marrow cells into nonirradiated recipients resulted in significant, although not permanent, prolongation of skin allograft survival without durable chimerism, suggesting that the introduction of alloantigens intraportally may favor the induction of nonresponsiveness to alloantigens even across strong major histocompatibility barriers. The relevance of these findings is discussed regarding the intraportal inoculation of allogeneic bone marrow cells for the treatment of genetic disorders in utero through the induction of neonatal tolerance.     

Repetitive DNA polymorphisms in following chimerism after allogeneic bone marrow transplantation

Information about the chimeric status of patients is of great importance in comparison of different conditioning and prophylactic regimens as well as for the post-bone marrow transplantation (BMT) therapies. In some cases, mixed chimerism (MC) can also be predictive of relapse. Analysis of the short tandem repeats (STR) loci by polymerase chain reaction (PCR) is a choice method for this purpose. In this study, we monitored 15 patients after BMT. Twelve of them underwent classical-conditioning regimen while the remaining three patients were subjected to non-myeloablative conditioning (minitransplantation). Evaluation of chimerism was performed using five STR and one variable number of tandem repeats (VNTR) locus. Four additional loci were PCR-amplified in cases of minitransplantation. Samples were analyzed by electrophoresis in an ALFexpress sequencer. MC was detected in seven cases of which it was predictive of relapse for two patients, who suffered from acute lymphocytic leukemia (ALL). The PCR-STR method proved to be a fast and relatively simple method, while the tested STR loci showed a high level of informativeness.     

利用脊柱骨来源骨髓细胞建立急性移植物抗宿主病模型

目的探讨利用脊柱骨来源骨髓细胞建立小鼠异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,Allo-HSCT)急性移植物抗宿主病(aGVHD)模型的可行性。方法选择C57BL/6(H-2b)雄性小鼠为供体鼠,BALB/c(H-2d)雌性小鼠为受体鼠。制备供体鼠的脾细胞和脊柱骨来源骨髓细胞悬液。受体鼠采用药物加小剂量辐照的预处理方式,于移植前8d～移植前4d腹腔注射氟达拉滨(200mg/kg),接着移植前3d～移植前1d腹腔注射环磷酰胺(60mg/kg),最后在移植前进行全身照射(total-body irradiation,TBI),照射剂量为4Gy(戈瑞)。18只受体鼠经预处理后随机分为3组,每组6只:(1)骨髓移植组,只输入1×107个脊柱骨来源骨髓细胞;(2)aGVHD组,输注1×107个脊柱骨来源骨髓细胞和5×106个脾细胞,建立aGVHD模型;(3)空白对照组,不输入任何细胞。观察3组小鼠生存状态及存活率,取aGVHD组与骨髓移植组存活21d的受体鼠进行病理学检查,取aGVHD组移植后21～28d存活的小鼠的脾脏进行流式细胞术检测骨髓细胞嵌合度。结果骨髓移植组小鼠全部存活,可重建造血,单纯输注骨髓细胞不会诱发aGVHD。aGVHD组小鼠出现aGVHD表现,100%发生aGVHD相关死亡,中位生存期为18d;病理检查结果显示符合aGVHD病理表现,移植后21～28d存活的小鼠诊断为供受体混合嵌合状态,符合aGVHD诊断标准。结论用脊柱骨来源骨髓建立的aGVHD模型完全符合标准,且更加经济,适合大规模建模。     

Spinal epidural lipomatosis following haploidentical allogeneic bone marrow transplantation for non-Hodgkin lymphoma

OBJECTIVES: Spinal epidural lipomatosis, is a very rare condition, usually seen as an uncommon complication of Cushing's syndrome secondary to chronic steroid therapy leading to increased fat deposits in the epidural space. CASE REPORT: We report the first documented case of acute symptomatic spinal epidural lipomatosis in a patient with relapsed non-Hodgkin lymphoma. The patient underwent an allogeneic bone marrow transplantation (BMT) and a month of steroid treatment for acute graft vs. host disease (GvHD). He presented with a mild to moderate Cushing's syndrome and minimal obesity. He progressed rapidly to paraparesis, sensory deficit, urinary incontinence and finally respiratory arrest complicated with staphylococcal sepsis. CONCLUSION: Epidural lipomatosis, with subacute thecal sac compression, is a possible life-threatening complication of relatively short-term systemic glucocorticoid therapy for GvHD in BMT setting.     

Pure red cell aplasia after major ABO-incompatible bone marrow transplantation: two case reports of treatment with recombinant human erythropoietin

A 34-year-old man with acute myelocytic leukemia (AML: MO) and a 32-year-old woman with AML: M2 developed pure red cell aplasia (PRCA) after receiving a major ABO-incompatible bone marrow transplant (BMT). The first patient responded to recombinant human erythropoietin (rhEPO) therapy, while the second did not. The second patient also received methylprednisolone (m-PSL) but developed reticulocytosis and hemolysis after the administration of m-PSL. Plasmapheresis was then performed and the patient promptly recovered from hemolysis and PRCA. We conclude that close attention must be paid when treating PRCA following major ABO-in-compatible BMT with rhEPO and m-PSL, as there is always the potential for massive hemolysis.     

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目的总结肝移植术后严重骨髓抑制并发症的临床特点,探讨其发生原因及预防措施。方法回顾性分析2002-2006年天津市第一中心医院收治的肝移植术后并发严重骨髓抑制6例病人的临床资料。结果所有病例均因终末期肝病进行肝脏移植,术后应用标准的免疫抑制剂方案:FK506 骁悉 激素,术后2周常规静脉用更昔洛韦预防巨细胞病毒感染。严重骨髓抑制(白细胞计数<1.0×109/L)发生于术后19~78d,临床表现包括发热伴有或不伴有皮疹、消化道症状、感染以致发生严重的败血症。5例肝功能在治疗过程中始终是正常的。所有病例均死于严重败血症及多脏器功能衰竭。结论肝移植术后严重骨髓抑制的发生可能与免疫反应、药物毒性及严重感染有关,其发生率及确切的发生机制尚不清楚。肝移植术后严重骨髓抑制一旦发生,预后极差,应根据可能的诱发因素采取积极的预防措施。     

异体骨预制骨皮瓣的实验研究

目的 探讨异体骨异位埋置预制骨皮瓣的可行性. 方法 从2010年11月至2011年7月,用广西巴马小型猪为实验动物,先制作深低温冷冻异体骨备用;异体骨经复温后置于旋髂浅动脉供养的皮瓣组织内,按植入部位不同分3组:皮下组(A组)、深筋膜下组(B组)、肌内组(C组),术后培养观察.指标:异体骨ECT显像(分别于术后第4周、第8周、第12周),血管造影检查、异体骨病理学检查(术后第12周). 结果 3组预制骨皮瓣术后ECT扫描显示:第8周和第12周异体骨植入部位放射性较4周时增高,差异有统计学意义(P＜0.05);血管造影显示在皮下组织、筋膜下组织、肌肉组织内的异体骨均有血管化,并与相应区域旋髂浅动脉建立血管联系;病理检查可见异体骨在筋膜下组织和肌肉组织内血管化作用和诱导新骨形成较明显. 结论 可以用异体骨异位埋置预制骨皮瓣.