血液辐照预防输血相关性移植物抗宿主病的发生

输血相关性移植物抗宿主病（TA-GVHD）,是指细胞免疫功能缺陷或受损的患者在接受输血过程中,输入了供者具有免疫活性的淋巴细胞,且不被受血者免疫系统所识别和排斥,使其在受者体内植活、增殖并攻击破坏受者体内的组织器官及造血系统,而引起的一系列病理症候群,是一种致命性的输血并发症。TA-GVHD虽然发病率低（0．01％～0．10％）,但死亡率极高（90％）,而且容易漏诊,     

警惕输血相关性移植物抗宿主病

警惕输血相关性移植物抗宿主病陈志哲临床医生熟知异基因骨髓移植并发的移植物抗宿主病，但对输血而引起的移植物抗宿主病相对地了解较少，这种输血相关性移植物抗宿主病（ＴＡ－ＧＶＨＤ）发病急、病死率高，而且容易漏诊。由于输血疗法（包括成分输血）在临床上的应用很...     

血制品照射预防免疫功能低下血液病患者的输血后移植物抗宿主病

目的 :比较在免疫功能低下人群输入照射及未照射血制品后输血相关移植物抗宿主病 (AT- GVHD)发生率。方法 :采用回顾性分析方法 ,照射组病例中所有血制品均需经射线照射处理 ,总剂量 2 0 0 0 c Gy,剂量率2 0 0 c Gy/ min。结果 :未照射组 2 0 0例免疫功能低下患者中 ,发现 4例患有 TA- GVHD,发生率 2 .0 % ;照射组 197例免疫功能低下患者中无 1例发生 TA- GVHD。结论 :在免疫功能低下人群输注含淋巴细胞血制品时应去除和灭活淋巴细胞 ,照射可减少 TA- GVHD的发生率。     

同种异基因骨髓移植中控制移植物抗宿主病和保留移植物抗白血病的新策略

同种异基因骨髓移植(allo-BMT)对白血病的治疗效果已得到广泛承认，然而移植物抗宿主病(GVHD)和白血病复发是移植成功的两个主要障碍。积累的研究已证明异基因骨髓移植物中的T淋巴细胞是GVHD重要效应细胞，同时具有移植物抗白血病(GVL)、抗感染和预防宿主抗移植物效     

血制品照射预防免疫功能低下血液病患者的输血后移植物抗宿 …

目的：比较在免疫功能低下人群输入照射及未照射血制品后输血相关移植物抗宿主病（ＡＴ－ＧＶＨＤ）发生率。方法：采用回顾性分析方法,照射组病例中所有血制品均需经射线照射处理,总剂量２０００ｃＧｙ,剂量率２００ｃＧｙ／ｍｉｎ。结果：未照射组２００例免疫功能低下患者中,发现４例患有ＴＡ－ＧＶＨＤ,发生率２．０％;照射组１９７例免疫功能低下患者中无１例发生ＴＡ－ＧＶＨＤ。结论：在免疫功能低下人群输注含淋巴细胞     

肝移植移植物抗宿主病的嵌合体检测及意义

肝移植移植物抗宿主病（GVHD）是一罕见并发症，发病率约占1％。1994-2002年行原位肝移植（OLT）的23452例患者中19例发生GVHD。GVHD通常发生在肝移植术后2～8周，病程急、病情凶险。典型临床表现为发热、皮疹、腹泻、全血细胞减少。但也有例外，Kuball等报道1例50岁女性原发性胆汁性肝硬化患者，接受32岁HLA纯合型儿子的肝脏，术后114d发生GVHD。2003年全球发生4例慢性GVHD。[第一段]     

非清髓性造血干细胞移植治疗白血病的初步临床疗效观察

目的:了解非清髓性造血干细胞移植(NST)的植入和初步临床疗效。方法:NST治疗恶性血液病18例,清髓性外周血干细胞移植(PBSCT)治疗24例。预处理方案:NST组主要包括单用马利兰(Bu)16mg/kg或Bu12mg/kg加阿糖胞苷(Arac)/高三尖杉酯碱(HHT)或一般联合化疗;清髓性PBSCT组包括环磷酰胺(Cy)120mg/kg加单次全身照射(STBI)9～10Gy或Bu16mg/kg/马法兰(Mel)140～160mg/m2加Arac。结果:NST组18例全部重建造血,移植相关死亡3例(16.67%);3年无病生存率(DFS)72.22%±10.56%,中位随访时间为2062(90～2730)d。清髓性PBSCT组造血重建23例,移植相关死亡4例(16.67%);3年DFS70.83%±9.28%,中位随访时间为1936(19～2700)d,两组差异无统计学意义(P>0.05)。NST组外周血象受抑程度明显减轻,WBC最低为0.3(0.2～0.9)×109/L,而清髓性PBSCT组16/24WBC降至0。NST组发生急性移植物抗宿主病(aGVHD)15(83.33%)例、可评估慢性移植物抗宿主病(cGVHD)16例(88.89%),均明显高于清髓性PBSCT组的6例(25%)与cGVHD13例(54.17%)。NST组发热13例(72.22%)而清髓性PBSCT组24例均有发热(100%),感染发生率和持续时间前者明显少于后者(P<0.05)。结论:NST与清髓性PBSCT疗效相当,造血重建快,且其外周血象受抑程度低,治疗安全、有效。     

骨髓移植术后急性肠道移植物抗宿主病内镜及病理学诊断研究

目的评价内镜和病理学诊断在急性肠道移植物抗宿主病(GVHD)中的作用。方法回顾性总结和分析2001—2005年北京大学人民医院血液病学研究所临床已确诊的23例急性肠道GVHD患者的内镜及病理学资料。结果内镜下表现可分为:黏膜大致正常、血管纹理模糊或消失、弥漫性黏膜充血、水肿和脆性增加,重者出现糜烂、溃疡,甚至黏膜脱落或出血;病理学表现提示:隐窝上皮细胞凋亡、缺失,隐窝结构破坏,上皮和黏膜固有层不同程度的淋巴细胞浸润。结论内镜和病理学检查可以用于急性肠道GVHD的诊断,尤其是内镜在急性肠道GVHD的早期诊断方面具有重要作用,同时结合病理学检查最终确立诊断。     

单倍体相合造血干细胞移植在难治高度恶性淋巴瘤中的应用

目的 :探讨应用单倍体相合骨髓移植对难治高度恶性非霍奇金淋巴瘤 (NHL)治疗的可行性。方法 :6例难治高度恶性NHL伴有骨髓浸润患者接受人白细胞抗原 (HLA) 2～ 3个位点不合的单倍体相合移植 ,供者用粒细胞集落刺激因子 (G CSF)促进后采髓 ,急性移植物抗宿主病 (GVHD)预防例 1采用环孢菌素A(CSA)、短程甲氨蝶呤 (MTX)、霉酚酸酯 (MMF)和抗胸腺细胞球蛋白 ,余 5例除上述药物外 ,还加用CD2 5单克隆抗体。结果 :6例移植后均获造血重建 ,粒细胞绝对数 >0 .5× 10 9/L中位天数是 17d ,血小板 >2 0× 10 9/L的中位天数是 2 2d ,骨髓植活直接证据检测证实为完全供者造血。 1例于移植后 2 0d时发生急性Ⅳ度肠道GVHD ,可评价慢性GVHD病例4例 ,均发生慢性GVHD ,其中 1例广泛性慢性GVHD ,口服泼尼松和CSA病情控制。中位随访 2 0 (7～ 4 2 )个月 ,1例重度GVHD于移植后 2个月死亡 ,1例在移植后 4个月并发真菌感染死亡 ,无病存活 4例 ,Karnofshy生存质量评价为 10 0 %。结论 :研究表明单倍体相合未经体外去T细胞骨髓移植对难治高度恶性NHL具有一定治疗价值 ,能够降低急性重症aGVHD发生和减少移植相关死亡。     

脐血移植治疗恶性血液病的临床研究

目的 :研究脐血移植 (CBT)在恶性血液病长期造血重建和移植物抗宿主病 (GVHD)及其他移植相关并发症发生情况。方法 :用CBT治疗恶性血液病 11例。供者均为患儿同胞 ,并于产前HLA配型 ,其中 9例完全相合 ,2例 4个位点相合。预处理选用Bu/Cy方案。仅用环孢素A(CsA)预防GVHD。脐血平均采集量 14 1(76～ 2 0 8)ml,输入有核细胞 (NCs)中位数 3.5 (1.5～ 10 .0 )× 10 7/kg。 结果 :9例造血重建 ,ANC >0 .5× 10 9/L的中位时间为 17(13～ 4 2 )d ,>1.0× 10 9/L中位时间为 2 1(16～ 5 0 )d ,PLT >2 0× 10 9/L中位时间为 2 6 (2 1～ 4 8)d ,>5 0× 10 9/L的中位时间为 4 5 (31～ 80 )d。DNA微卫星位点检测 ,2 8～ 90d呈现完全嵌合。其中 3例发生Ⅰ～Ⅱ度急性GVHD ,1例Ⅲ～Ⅳ度急性GVHD ,3例发生慢性局限性GVHD ,2例未植活。结论 :①同胞HLA相合脐血移植安全、有效。②CBT造血恢复时间与输入有核细胞数有关 ,最好NCs≥ 3.5× 10 7/kg。③Bu/Cy方案副作用小 ,是儿童造血干细胞移植安全有效的预处理方案。④HLA相合者仅用CsA即可预防GVHD。     

间充质干细胞治疗糖皮质激素耐药性慢性移植物抗宿主病临床疗效观察

目的 探讨间充质干细胞(MSC)治疗糖皮质激素(激素)耐药性慢性移植物抗宿主病(cGVHD)的疗效及作用机制.方法 12例激素耐药性cGVHD患者在原有免疫抑制剂基础上联合MSC治疗.12例患者共接受24例次MSC输注,17例次MSC来自第二方,7例次来源于第三方,其中1例输注1次、10例输注2次、1例输注3次.首次输注细胞量1.0(0.4～2.1)×106/kg,第2次输注1.2(0.8～1.9)×106/kg,末次输注细胞量为1.1×106/kg.5例接受2例不同供者MSC输注.并分别于MSC治疗前、治疗后4周应用流式细胞仪检测患者外周血CD+3、CD+4、CD+8、CD+19、CD+4CD+25、FOXF3+、FOXP3+CD+4及FOXP3+CD+25淋巴细胞亚群比例.结果 12例患者接受MSC输注后3例获得完全缓解(CR)、6例获得部分缓解(PR),总有效率(CR+PR)为75%(9/12).3例CB患者在MSc治疗471(372～731)d后停用免疫抑制剂,随访129(100～292)d cGVHD无复发;6例PR患者在MSC治疗64(60～79)d后开始进入免疫抑制剂减量阶段,目前除1例继发舌瘤致死外,其他患者应用小剂量免疫抑制剂维持治疗随访中位生存时间1152(795～1914)d病情仍稳定并存活.3例无效患者中,1例疾病稳定患者目前仍需联合三种免疫抑制剂治疗,另2例疾病进展患者分别于输注MSC8个月及10个月后死于白血病复发及肺脏cGVHD.输注MSC后12例患者CD4/CD8比例及调节性T细胞均显著升高,B细胞无明显改变.结论 第二方或第三方来源的Msc对于治疗激素耐药性cGVHD具有一定疗效,其作用机制可能与提高CD4/CD8比例及诱导调节性T细胞形成有关.     

移植物抗宿主病的防治研究进展

异基因造血干细胞移植是根治恶性血液病的最有效方法，移植物抗宿主病(GVHD)是影响其疗效的主要并发症之一。通过降低颈处理强度、细胞因子屏蔽、阻断协同刺激信号、诱导嵌合状态等手段可改善GVHD，但如何同时保留移植物抗白血府肿瘤效应仍有待完善。本文就GVHD的发病机制及近年的防治进展作一综述。     

肺癌化疗后输血相关性移植物抗宿主病患者一例的护理报告

<正>输血相关性移植物抗宿主病(transfusion associated graft versus host disease,TA-GVHD)是输血最严重并发症之一,是严重危及受者生命,与输血密切相关的一组疾病~([1-2])。其发生的条件为输入的血液中含有一定数量的具有免疫活性的淋巴细胞,供体与受体之间存在组织相容性及受者的免疫功能低下~([3-4])。供、受体淋巴细胞相互作用,激活并使供者的T细胞克隆性扩增,导致细胞因子释放,继而损伤受者     

细胞因子与慢性移植物抗宿主病关系研究

慢性移植物抗宿主病(cGVHD)是异基因造血干细胞移植(allo-HSCT)晚期最常见的并发症之一和主要死亡原因,存活半年以上受者中30%~50%可出现cGVHD。近年来,随着对cGVHD发生机制研究的逐步深入,认为cGVHD是同种异体免疫反应和自身免疫反应现象相联系的机体重度免疫缺陷。其发生和发     

间充质干细胞治疗糖皮质激素耐药性慢性移植物抗宿主病临床疗效观察

Objective To assess whether treatment with mesenchymal stem cells (MSCs) is an effective adjunct therapy for refractory extensive chronic graft-versus-host disease (GVHD) resistant to conventional therapy. Methods 12 patients with steroid-resistant extensive chronic GVHD were treated with MSCs. One patient received one dose, 10 received two doses, and the remaining three doses. The MSCs were obtained from HI,A-identical sibling donors (n = 14), haploidentical donors (n = 2), unrelated mismatched donor (n = 1) and third-party HLA-mismatched donors (n = 7). Of the 11 patients treated with multiple infusions, 5 received cells derived from two donors. The median first dose of MSCs was 1.0 (0. 4-2. 1) × 106/kg , the median second dose was 1.2(0. 8-1.9) × 106/kg , and the third dose in one patient was 1.1 × 106/kg. Meanwhile the proportion of CD3+ ,CD4+,CD8+ ,CD19+,CD4+ CD25+ ,FOXP3+,FOXP3+CD4+ and FOXP3+ CD25+ was determined with double fluorescent-labeled antibodies and flow cytometry before and 4 weeks after the MSCs infusion. Results No patients had side-effects during or immediately after the infusions of MSCs. After a treatment course of one to three doses, 3 patients had complete response(CR), 6 showed partial response(PR) and 3 did not respond; the total effective rate was 75% (9/12). Complete resolution was seen in the involvement of skin (3/12), lung (1/3), joints (1/5), liver (3/10), oralcavity (4/12) and eye (2/7). Response rate was not related to donor HLA-match. 3 CR patients discontinued all of the immunosuppressive agents without relapse 100 to 292 days after the MSC infusion and 6 PR patients taped all immunosuppressive agents after 60 to 79 days. Mean follow-up period was 1152(795-1914) days, leukemia free survival rate was 91.7% (11/12) and the overall survival rate was 75% (9/12). The ratio of CD4/CD8 and the proportion of regulatory T cells were significantly higher than that before MSCs treatment. Conclusion Third-party MSCs were as effective as HLA-identical or haploidentical cells. This finding has practical implications and suggests that third-party cells can be prepared and stored frozen to be used for steroid-resistant extensive chronic GVHD therapy. It is concluded that MSCs may prevent the lethal cGVHD after allogeneic hematopoietic stem cell transplantation and raise the survival rate by increasing the ratio of CD4/CD8 and proportion of regulatory T cells in vivo.     

间充质干细胞治疗糖皮质激素耐药性慢性移植物抗宿主病临床疗效观察

Objective To assess whether treatment with mesenchymal stem cells (MSCs) is an effective adjunct therapy for refractory extensive chronic graft-versus-host disease (GVHD) resistant to conventional therapy. Methods 12 patients with steroid-resistant extensive chronic GVHD were treated with MSCs. One patient received one dose, 10 received two doses, and the remaining three doses. The MSCs were obtained from HI,A-identical sibling donors (n = 14), haploidentical donors (n = 2), unrelated mismatched donor (n = 1) and third-party HLA-mismatched donors (n = 7). Of the 11 patients treated with multiple infusions, 5 received cells derived from two donors. The median first dose of MSCs was 1.0 (0. 4-2. 1) × 106/kg , the median second dose was 1.2(0. 8-1.9) × 106/kg , and the third dose in one patient was 1.1 × 106/kg. Meanwhile the proportion of CD3+ ,CD4+,CD8+ ,CD19+,CD4+ CD25+ ,FOXP3+,FOXP3+CD4+ and FOXP3+ CD25+ was determined with double fluorescent-labeled antibodies and flow cytometry before and 4 weeks after the MSCs infusion. Results No patients had side-effects during or immediately after the infusions of MSCs. After a treatment course of one to three doses, 3 patients had complete response(CR), 6 showed partial response(PR) and 3 did not respond; the total effective rate was 75% (9/12). Complete resolution was seen in the involvement of skin (3/12), lung (1/3), joints (1/5), liver (3/10), oralcavity (4/12) and eye (2/7). Response rate was not related to donor HLA-match. 3 CR patients discontinued all of the immunosuppressive agents without relapse 100 to 292 days after the MSC infusion and 6 PR patients taped all immunosuppressive agents after 60 to 79 days. Mean follow-up period was 1152(795-1914) days, leukemia free survival rate was 91.7% (11/12) and the overall survival rate was 75% (9/12). The ratio of CD4/CD8 and the proportion of regulatory T cells were significantly higher than that before MSCs treatment. Conclusion Third-party MSCs were as effective as HLA-identical or haploidentical cells. This finding has practical implications and suggests that third-party cells can be prepared and stored frozen to be used for steroid-resistant extensive chronic GVHD therapy. It is concluded that MSCs may prevent the lethal cGVHD after allogeneic hematopoietic stem cell transplantation and raise the survival rate by increasing the ratio of CD4/CD8 and proportion of regulatory T cells in vivo.     

间充质干细胞治疗糖皮质激素耐药性慢性移植物抗宿主病临床疗效观察

Objective To assess whether treatment with mesenchymal stem cells (MSCs) is an effective adjunct therapy for refractory extensive chronic graft-versus-host disease (GVHD) resistant to conventional therapy. Methods 12 patients with steroid-resistant extensive chronic GVHD were treated with MSCs. One patient received one dose, 10 received two doses, and the remaining three doses. The MSCs were obtained from HI,A-identical sibling donors (n = 14), haploidentical donors (n = 2), unrelated mismatched donor (n = 1) and third-party HLA-mismatched donors (n = 7). Of the 11 patients treated with multiple infusions, 5 received cells derived from two donors. The median first dose of MSCs was 1.0 (0. 4-2. 1) × 106/kg , the median second dose was 1.2(0. 8-1.9) × 106/kg , and the third dose in one patient was 1.1 × 106/kg. Meanwhile the proportion of CD3+ ,CD4+,CD8+ ,CD19+,CD4+ CD25+ ,FOXP3+,FOXP3+CD4+ and FOXP3+ CD25+ was determined with double fluorescent-labeled antibodies and flow cytometry before and 4 weeks after the MSCs infusion. Results No patients had side-effects during or immediately after the infusions of MSCs. After a treatment course of one to three doses, 3 patients had complete response(CR), 6 showed partial response(PR) and 3 did not respond; the total effective rate was 75% (9/12). Complete resolution was seen in the involvement of skin (3/12), lung (1/3), joints (1/5), liver (3/10), oralcavity (4/12) and eye (2/7). Response rate was not related to donor HLA-match. 3 CR patients discontinued all of the immunosuppressive agents without relapse 100 to 292 days after the MSC infusion and 6 PR patients taped all immunosuppressive agents after 60 to 79 days. Mean follow-up period was 1152(795-1914) days, leukemia free survival rate was 91.7% (11/12) and the overall survival rate was 75% (9/12). The ratio of CD4/CD8 and the proportion of regulatory T cells were significantly higher than that before MSCs treatment. Conclusion Third-party MSCs were as effective as HLA-identical or haploidentical cells. This finding has practical implications and suggests that third-party cells can be prepared and stored frozen to be used for steroid-resistant extensive chronic GVHD therapy. It is concluded that MSCs may prevent the lethal cGVHD after allogeneic hematopoietic stem cell transplantation and raise the survival rate by increasing the ratio of CD4/CD8 and proportion of regulatory T cells in vivo.     

间充质干细胞治疗糖皮质激素耐药性慢性移植物抗宿主病临床疗效观察

Objective To assess whether treatment with mesenchymal stem cells (MSCs) is an effective adjunct therapy for refractory extensive chronic graft-versus-host disease (GVHD) resistant to conventional therapy. Methods 12 patients with steroid-resistant extensive chronic GVHD were treated with MSCs. One patient received one dose, 10 received two doses, and the remaining three doses. The MSCs were obtained from HI,A-identical sibling donors (n = 14), haploidentical donors (n = 2), unrelated mismatched donor (n = 1) and third-party HLA-mismatched donors (n = 7). Of the 11 patients treated with multiple infusions, 5 received cells derived from two donors. The median first dose of MSCs was 1.0 (0. 4-2. 1) × 106/kg , the median second dose was 1.2(0. 8-1.9) × 106/kg , and the third dose in one patient was 1.1 × 106/kg. Meanwhile the proportion of CD3+ ,CD4+,CD8+ ,CD19+,CD4+ CD25+ ,FOXP3+,FOXP3+CD4+ and FOXP3+ CD25+ was determined with double fluorescent-labeled antibodies and flow cytometry before and 4 weeks after the MSCs infusion. Results No patients had side-effects during or immediately after the infusions of MSCs. After a treatment course of one to three doses, 3 patients had complete response(CR), 6 showed partial response(PR) and 3 did not respond; the total effective rate was 75% (9/12). Complete resolution was seen in the involvement of skin (3/12), lung (1/3), joints (1/5), liver (3/10), oralcavity (4/12) and eye (2/7). Response rate was not related to donor HLA-match. 3 CR patients discontinued all of the immunosuppressive agents without relapse 100 to 292 days after the MSC infusion and 6 PR patients taped all immunosuppressive agents after 60 to 79 days. Mean follow-up period was 1152(795-1914) days, leukemia free survival rate was 91.7% (11/12) and the overall survival rate was 75% (9/12). The ratio of CD4/CD8 and the proportion of regulatory T cells were significantly higher than that before MSCs treatment. Conclusion Third-party MSCs were as effective as HLA-identical or haploidentical cells. This finding has practical implications and suggests that third-party cells can be prepared and stored frozen to be used for steroid-resistant extensive chronic GVHD therapy. It is concluded that MSCs may prevent the lethal cGVHD after allogeneic hematopoietic stem cell transplantation and raise the survival rate by increasing the ratio of CD4/CD8 and proportion of regulatory T cells in vivo.     

间充质干细胞治疗糖皮质激素耐药性慢性移植物抗宿主病临床疗效观察

Objective To assess whether treatment with mesenchymal stem cells (MSCs) is an effective adjunct therapy for refractory extensive chronic graft-versus-host disease (GVHD) resistant to conventional therapy. Methods 12 patients with steroid-resistant extensive chronic GVHD were treated with MSCs. One patient received one dose, 10 received two doses, and the remaining three doses. The MSCs were obtained from HI,A-identical sibling donors (n = 14), haploidentical donors (n = 2), unrelated mismatched donor (n = 1) and third-party HLA-mismatched donors (n = 7). Of the 11 patients treated with multiple infusions, 5 received cells derived from two donors. The median first dose of MSCs was 1.0 (0. 4-2. 1) × 106/kg , the median second dose was 1.2(0. 8-1.9) × 106/kg , and the third dose in one patient was 1.1 × 106/kg. Meanwhile the proportion of CD3+ ,CD4+,CD8+ ,CD19+,CD4+ CD25+ ,FOXP3+,FOXP3+CD4+ and FOXP3+ CD25+ was determined with double fluorescent-labeled antibodies and flow cytometry before and 4 weeks after the MSCs infusion. Results No patients had side-effects during or immediately after the infusions of MSCs. After a treatment course of one to three doses, 3 patients had complete response(CR), 6 showed partial response(PR) and 3 did not respond; the total effective rate was 75% (9/12). Complete resolution was seen in the involvement of skin (3/12), lung (1/3), joints (1/5), liver (3/10), oralcavity (4/12) and eye (2/7). Response rate was not related to donor HLA-match. 3 CR patients discontinued all of the immunosuppressive agents without relapse 100 to 292 days after the MSC infusion and 6 PR patients taped all immunosuppressive agents after 60 to 79 days. Mean follow-up period was 1152(795-1914) days, leukemia free survival rate was 91.7% (11/12) and the overall survival rate was 75% (9/12). The ratio of CD4/CD8 and the proportion of regulatory T cells were significantly higher than that before MSCs treatment. Conclusion Third-party MSCs were as effective as HLA-identical or haploidentical cells. This finding has practical implications and suggests that third-party cells can be prepared and stored frozen to be used for steroid-resistant extensive chronic GVHD therapy. It is concluded that MSCs may prevent the lethal cGVHD after allogeneic hematopoietic stem cell transplantation and raise the survival rate by increasing the ratio of CD4/CD8 and proportion of regulatory T cells in vivo.     

间充质干细胞治疗糖皮质激素耐药性慢性移植物抗宿主病临床疗效观察

Objective To assess whether treatment with mesenchymal stem cells (MSCs) is an effective adjunct therapy for refractory extensive chronic graft-versus-host disease (GVHD) resistant to conventional therapy. Methods 12 patients with steroid-resistant extensive chronic GVHD were treated with MSCs. One patient received one dose, 10 received two doses, and the remaining three doses. The MSCs were obtained from HI,A-identical sibling donors (n = 14), haploidentical donors (n = 2), unrelated mismatched donor (n = 1) and third-party HLA-mismatched donors (n = 7). Of the 11 patients treated with multiple infusions, 5 received cells derived from two donors. The median first dose of MSCs was 1.0 (0. 4-2. 1) × 106/kg , the median second dose was 1.2(0. 8-1.9) × 106/kg , and the third dose in one patient was 1.1 × 106/kg. Meanwhile the proportion of CD3+ ,CD4+,CD8+ ,CD19+,CD4+ CD25+ ,FOXP3+,FOXP3+CD4+ and FOXP3+ CD25+ was determined with double fluorescent-labeled antibodies and flow cytometry before and 4 weeks after the MSCs infusion. Results No patients had side-effects during or immediately after the infusions of MSCs. After a treatment course of one to three doses, 3 patients had complete response(CR), 6 showed partial response(PR) and 3 did not respond; the total effective rate was 75% (9/12). Complete resolution was seen in the involvement of skin (3/12), lung (1/3), joints (1/5), liver (3/10), oralcavity (4/12) and eye (2/7). Response rate was not related to donor HLA-match. 3 CR patients discontinued all of the immunosuppressive agents without relapse 100 to 292 days after the MSC infusion and 6 PR patients taped all immunosuppressive agents after 60 to 79 days. Mean follow-up period was 1152(795-1914) days, leukemia free survival rate was 91.7% (11/12) and the overall survival rate was 75% (9/12). The ratio of CD4/CD8 and the proportion of regulatory T cells were significantly higher than that before MSCs treatment. Conclusion Third-party MSCs were as effective as HLA-identical or haploidentical cells. This finding has practical implications and suggests that third-party cells can be prepared and stored frozen to be used for steroid-resistant extensive chronic GVHD therapy. It is concluded that MSCs may prevent the lethal cGVHD after allogeneic hematopoietic stem cell transplantation and raise the survival rate by increasing the ratio of CD4/CD8 and proportion of regulatory T cells in vivo.