异基因造血干细胞移植后急性移植物抗宿主病的临床分析

目的 探讨异基因造血干细胞移植（allo-HSCT）后急性移植物抗宿主病（aGVHD）的临床特征及疗效.方法 118例造血系统疾病患者接受allo-HSCT,可评估aGVHD者113例;回顾性研究分析aGVHD患者的临床特征和疗效.结果 发生aGVHD者54例（47.8%）,中位发病时间27天;研究发现,aGVHD患者对一线治疗有效率为66.7%,其中,32例Ⅱ～Ⅳ度aGVHD患者对甲泼尼龙有效者15例（46.9%）,激素治疗无效的aGVHD患者对二线治疗效果不佳（30.8%）;aGVHD治疗后感染并发症是导致患者死亡的主要原因,尤其见于Ⅲ～Ⅳ度aGVHD患者.移植后180天存活率分别为：0度aGVHD（89.7±4.6）%、Ⅰ度aGVHD（90.5±6.4）%,Ⅱ度aGVHD（84.7±8.1）%,Ⅲ～Ⅳ度aGVHD（32.8±24.2）%,表明Ⅲ～Ⅳ度aGVHD对移植患者早期生存有严重不良影响（P＜0.05）.结论 aGVHD是allo-HSCT后常见并发症和致死原因,感染是影响aGVHD疗效的重要原因.     

异基因造血干细胞移植后中枢神经系统移植物抗宿主病的研究进展

正异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)是对多种血液病治疗有效、甚至是唯一可治愈的治疗手段。研究[1～4]显示,allo-HSCT后中枢神经系统并发症(central nervous system complication,CNSC)发病率在8%～42%,而病死率在40%～70%,严重影响移植后患者长期生存。CNSC可分为药物毒性、感染性、代谢性、脑血管性、免疫性、肿瘤性并发症及微血管血栓病变,而中枢神经系统移植物抗宿主病(central nervous system graftversus-host disease,CNS-GVHD)是免疫性CNSC中的一种特殊类型[3]。由于脑组织难于获取,CNS-GVHD很     

151例异基因造血干细胞移植急性移植物抗宿主病的临床研究

目的 分析造血干细胞来源、人白细胞抗原(HLA)配型、移植方式、预处理方案与急性移植物抗宿主病(aGVHD)的关系,为临床治疗选择最佳方案,降低aGVHD的发生率和严重程度.方法 对151例异基因造血干细胞移植患者的临床资料进行统计学分析.结果 亲缘与非亲缘之间、HLA配型之间、骨髓移植与外周血造血干细胞移植之间的aGVHD发生率有统计学差异(P＜0.05);有无全身照射(TBI)的预处理方案之间的aGVHD发生率无统计学差异(P＜0.05).结论 非血缘关系、HLA配型不全相合的骨髓移植是aGVHD发生的主要危险因素.     

异基因造血干细胞移植后T细胞免疫重建与移植物抗宿主病

异基因造血干细胞移植(Allo-HSCT)后的免疫重建与移植物抗肿瘤／白血病(GVT／GVL)效应,及移植物抗宿主病(GVHD)、移植后感染等均有密切关系。T细胞是细胞免疫、体液免疫的调节与效应细胞,在移植后的免疫重建中占有重要位置。由于供者T细胞活化是GVHD发生的关键环     

异基因造血干细胞移植后重度肠道急性移植物抗宿主病的治疗经验探讨

异基因造血干细胞移植(allo-HSCT)是治疗恶性血液病的有效手段,而急性移植物抗宿主病(aGVHD)目前仍是异基因造血干细胞移植的最严重的并发症之一,也是导致移植失败和死亡的重要原因之一[1,2].     

异基因造血干细胞移植后单独胃肠道受累急性移植物抗宿主病的临床特征

目的 分析异基因造血干细胞移植(allo-HSCT)后患者发生单独累及胃肠道的急性移植物抗宿主病(aGVHD)的临床特征.方法 回顾性总结2007年11月至2008年12月在我院行allo-HSCT治疗的307例血液病患者的临床资料,分析单独胃肠道受累的aGVHD的临床特征、危险因素、治疗效果及预后.结果 307例患者中174例(56.7%)发生aGVHD,其中单独累及胃肠道的38例,占21.8%.单独累及胃肠道的aGVHD的发生与受者性别、年龄、供受者性别关系、供受者血型关系、基础疾病诊断及回输的单个核细胞均无关;但与移植类型相关,亲缘全相合组发生率高于亲缘不合组及非血缘组.单独累及胃肠道的aGVHD患者经糖皮质激素或抗CD25单克隆抗体治疗,仅有2例死于aGVHD未控制合并感染,总有效率达94.7%;发生Ⅱ～Ⅳ度aGVHD但非单独累及胃肠道的患者抗aGVHD治疗总有效率为85.2%;组间比较差异有统计学意义(P=0.015).单独累及胃肠道的aGVHD中有12例应用抗CD25单克隆抗体治疗,治疗均有效.结论 HSCT后单纯累及胃肠道的aGVHD并不少见,其发生率在亲缘全相合组高于亲缘不全相合组及非血缘组,单独累及胃肠道的aGVHD对抗aGVHD治疗效果好,可能与应用抗CD25单克隆抗体疗效较好有关.     

异基因造血干细胞移植患者血清抗HLA抗体检测的意义

目的研究血清抗HLA抗体与异基因造血干细胞移植（allo．HSCT）后移植物被排斥、疾病复发及移植物抗宿主病（GVHD）的关系。方法20例allo—HSCT患者在移植前与移植后1、3、6个月动态检测抗HLA抗体。结果移植前抗HLA抗体≥30％与〈30％的患者发生原发植入失败比较无显著性差异（P〉0．05）;在成功植入的17例患者中,移植前和（或）移植后抗HLA抗体I〉30％的5例患者均发生移植物被排斥或疾病复发,而抗HLA抗体均〈30％的12例患者中仅有1例发生,两者有显著性差异（P〈0．005）。移植后抗HLA抗体呈动态升高的3例患者均在植入后且抗HLA抗体〉130％时发生移植物被排斥和疾病复发,而呈动态降低的5例患者仅有1例在植入后发生移植物被排斥。移植前和（或）移植后抗HLA抗体≥30％的5例患者均未发生GVHD;而抗HLA抗体〈30％的12例患者中有9例发生急性和（或）慢性GVHD,发生率75％,两者有显著性差异（P〈0．005）。结论对allo．HSCT受者在移植前、后动态检测抗HLA抗体有助于预测移植物被排斥、疾病复发与GVHD的发生,抗HLA抗体〉130％或呈动态升高者继发植入失败或疾病复发的发生率高,而GVHD发生率较低。     

异基因造血干细胞移植后并发严重移植物抗宿主病1例

患者,男,35岁,2007年1月诊断慢性粒细胞白血病（CML）-慢性期,3月查bcr／abl融合基因阳性率为12．1％,6月行同胞间HLA全相合异基因外周血造血干细胞移植（allo—PBSCT）术。移植后40d复查bcr／abl融合基因阳性率0．02％;移植后90d复查bcr／abl融合基因阳性率0．57％;血常规正常,骨髓细胞学检查提示增生性骨髓像,粒系各阶段比例正常。逐渐停用环孢素。停药20d出现背部、双侧大腿皮肤丘疹伴瘙痒;口腔干燥,颊黏膜粗糙,进食辛辣食物时口腔黏膜疼痛。移植后120d出现咳嗽、咯少量白色泡沫痰。     

异基因造血干细胞移植术后移植物抗宿主病的研究进展

造血干细胞移植（HSCT）特别是异基因造血干细胞移植（allo—HSCT）越来越多地用于治疗恶性血液系统疾病,而移植后出现的移植物抗宿主病（GVHD）是allo-HSCT的主要并发症和死亡原因之一。移植物抗宿主病按发生时间分为急性移植物抗宿主病（aGVHD）和慢性移植物抗宿主病（cGVHD）。     

异基因造血干细胞移植后100 d内腹泻病因分析

目的 回顾性分析异基因造血干细胞移植(Allo-HSCT)后100 d内腹泻的临床特点及病因谱.方法 总结北京大学人民医院2006年9月至2007年3月125例Allo-HSCT患者移植后100 d内的资料.结果 76例发生移植后腹泻的患者累计发病114例次,总发生率60.8%(76/125).病因分析显示,预处理毒性62例次(54.4%),急性移植物抗宿主病(aGVHD)32例次(28.1%),感染性腹泻15例次(13.2%),血栓性微血管病(TMA)及植入综合征各2例次,治疗相关性腹泻1例次.76例移植后腹泻治愈72例,死亡4例(5.3%).Cox回归分析显示,HLA配型不合(R=6.643,P=0.026)及高危疾病状态(R=3.749,P=0.001)是腹泻发生的危险因素.结论 腹泻是Allo-HSCT后的常见症状,其病因包括感染和非感染因素,针对病因的治疗可以改善预后.     

多种细胞因子与急性移植物抗宿主病发病关系的研究

目的:探讨异基因造血干细胞移植(allo-HSCT)患者不同时期血清细胞因子(CK)水平与急性移植物抗宿主病(aGVHD)严重程度的关系。方法:于移植前、移植后2、4、8、12周用流式微球技术监测17例allo-HSCT患者血清细胞因子(TNF-α、IFN-γI、L-2I、L-4I、L-6及IL-10)水平的动态变化。结果:Ⅱ~Ⅳ度aGVHD患者组(5/17)与0~Ⅰ度aGVHD患者组(12/17)相比:移植后8、12周血清IFN-γ浓度(ng/L)前者较后者显著增高(13.66±1.16,14.10±0.42对比10.00±0.28,11.14±1.13)(P<0.05);移植后12周血清IL-6浓度(ng/L)前者较后者显著增高(10.17±1.07对比6.97±1.18,P<0.05);其余各时期细胞因子浓度对比无明显差异。结论:异基因造血干细胞移植后,发生Ⅱ~Ⅳ度aGVHD患者较0~Ⅰ度aGVHD患者血清IFN-γ与IL-6浓度较高,为炎性免疫反应加重表现;TNF-αI、L-2I、L-4及IL-10水平两组间无显著差异,很可能受aGVHD严重程度、免疫抑制剂应用、免疫细胞功能恢复延迟等多因素影响。     

Increased serum levels of matrix metalloproteinase-9 in acute graft-versus-host disease after allogeneic haematopoietic stem cell transplantation

Matrix metalloproteinases (MMPs) have been implicated in a variety of normal and pathological conditions that involve matrix degradation and remodelling. We investigated the role of MMPs in acute graft-versus-host disease (aGVHD) in 29 patients who had undergone allogeneic haematopoietic stem cell transplantation. The present study showed that the serum levels of MMP-9, but not those of MMP-2, significantly correlated with the occurrence and severity of aGVHD. Moreover, immunohistochemical analysis of the cutaneous lesions of patients with aGVHD revealed an increased number of inflammatory cells positive for MMP-9. These results suggest that MMP-9 might play an important role in the pathogenesis of aGVHD.     

Association between interleukin-10 promoter gene polymorphisms and acute graft-versus-host disease after hematopoietic stem cell transplantation: A systematic review and meta-analysis

Abstract

Objectives

Interleukin-10 (IL-10) is an important immunomodulatory cytokine. The association between IL-10 promoter gene polymorphisms and acute graft-versus-host disease (aGVHD) risk is established; however, results of these studies remain inconclusive. We performed a meta-analysis to clarify the effects of IL-10 promoter gene polymorphisms on aGVHD risk.

Methods

The authors searched MEDLINE, EMBASE, and Cochrane Library databases. Two independent authors extracted data, and the effects were estimated from an odds ratio (OR) with 95% confidence intervals (CIs). Subgroup and sensitivity analyses identified sources of heterogeneity.

Results

Finally, a total of 11 studies encompassing 3588 recipients and 3221 donors were included to study IL-10 -1082 G > A, -819 C > T, and -592 C > A polymorphisms. IL-10 -819 CC genotype was associated with an increased aGVHD risk (grade I–IV: OR, 2.722 (95% CI, 1.360–5.450); grade II–IV: OR, 2.265 (95% CI, 1.015–5.053)). Furthermore, patients who received grafts from donors with an IL-10 -819 CC genotype experienced more frequent grade I–IV aGVHD (OR, 2.306 (95% CI, 1.168–4.551)). Recipients with IL-10 -592 CC genotypes were at increased risk for grade II–IV aGVHD (OR, 1.999 (95% CI, 1.230–3.250)). Together, this meta-analysis found that IL-10 -819 CC and -592 CC polymorphisms increased aGVHD risk.

Discussion and Conclusion

This meta-analysis found the evidence that the IL-10 -819 CC and -592 CC genotypes in both recipients and donors increased the risk of aGVHD in allogeneic hematopoietic stem cell transplantation (HSCT) patients. These results contribute towards improving patient outcome through insight and rationale for individualized treatment strategies considering genetic determinants.     

Acute eosinophilic pneumonia after allogeneic hematopoietic stem cell transplantation

A 55-year old woman with multiple myeloma was treated with hematopoietic stem cell transplantation (HSCT). She developed cutaneous and hepatic graft-vs-host disease (GVHD). Sixty-five days after HSCT, acute respiratory failure occurred. A thoracic computed tomography scan showed bilateral patchy infiltrates. Bronchoalveolar lavage revealed 40% eosinophils on differential cell count with no infectious pathogens. These findings were in favor of acute eosinophilic pneumonia. High-dose steroid treatment was started, which had a rapid and lasting favorable course. After HSCT, clinicians should be aware that acute eosinophilic pneumonia mimics infectious pneumonitis and can be associated with GVHD.     

成人人类白细胞抗原全相合与不相合造血干细胞移植后急性移植物抗宿主病的临床特点与预后

 目的 比较成人人类白细胞抗原(HLA)全相合与HLA不相合异基因造血干细胞移植(allo-HSCT)后急性移植物抗宿主病(aGVHD)的临床特点与疗效。方法 回顾性分析2010年1月至2011年12月于北京大学血液病研究所进行亲缘allo-HSCT患者的临床病历资料,分析不同类型移植后aGVHD的发病类型与特点以及临床疗效的差异。结果 544例患者中,HLA不相合移植后的aGVHD发生率为50.2%,明显高于HLA全相合移植(20.4%,P<0.001),且发生得更早,但Ⅲ°~Ⅳ° aGVHD的累积发生率两组之间差异并无统计学意义(4.5%比6.8%, P=0.066);全相合移植中肠道aGVHD发生率较高(31.1%),而在不相合移植中以皮肤aGVHD为主(66.5%),肠道和肝脏aGVHD发生率均较全相合移植低;全相合移植发生aGVHD时发热患者比例较不相合移植低(28.9% 比47.6%,P=0.028);全相合移植与不相合移植相比,aGVHD总体治愈率低,特别是Ⅲ°~Ⅳ° aGVHD最终疗效差,二线治疗后的完全缓解率低于不相合移植(88.9%比98.8%,P=0.006),aGVHD相关病死率高于不相合移植(11.1%比2.4%,P=0.024)。结论 HLA不相合移植后aGVHD发生率明显高于全相合患者,但重度aGVHD发生率两组间差异无统计学意义,两组患者一线治疗缓解率相近,但HLA不相合移植患者二线治疗后aGVHD总体缓解率更高。     

非血缘造血干细胞移植现状与问题

异基因造血干细胞移植(Allo HSCT)是某些血液系统恶性疾病惟一有望治愈的手段,也是某些血液系统非恶性疾病的重要治疗手段。HLA相合同胞供者是Allo HSCT首选的供者来源,但是只有部分患者可以找到相合的同胞供者。因此,寻找合适的非血缘供者就变得十分重要。近年来,随着移植技术方案的成熟和支持治疗的进步,移植现状已获得明显的改善,非血缘供者造血干细胞移植疗效已达到了与同胞供者移植接近的水平。     

Recombinant human soluble tumor necrosis factor receptor fusion protein as treatment for steroid refractory graft-versus-host disease following allogeneic hematopoietic stem cell transplantation

Etanercept is a recombinant human soluble tumor necrosis factor (TNF-alpha) receptor fusion protein that inhibits TNF-alpha, a major mediator in the pathogenesis of graft-versus-host disease (GVHD). The purpose of our study was to evaluate the safety and efficacy of etanercept therapy in 21 patients with steroid-refractory acute GVHD (aGVHD) (n = 13) and chronic GVHD (cGVHD) (n = 8). Etanercept 25 mg was given subcutaneously twice weekly for 4 weeks followed by 25 mg weekly for 4 weeks. At the time of initiation of etanercept, 14 patients had skin, 13 had gastro-intestinal, 5 had liver, 5 had pulmonary, and 4 had oral involvement. Twelve patients (57%) completed 12 doses of therapy. Overall, 11 of 21 patients (52%) responded to the treatment with etanercept, including 6 patients (46%) with aGVHD [n = 4 complete response (CR), n = 2 partial response (PR)] and 5 patients (62%) with cGVHD (n = 1 CR, n = 4 PR). Clinical responses were most commonly seen in patients with refractory gut aGVHD with 55% of the patients having a CR and 9% having a PR. CMV reactivation occurred in 48% of patients, bacterial infections in 14% of patients, and fungal infections in 19% of patients. Fourteen patients (67%) were alive after a median follow-up of 429 days (range 71-1007 days) since initiation of etanercept. Seven patients died, 3 of infections, 2 of refractory aGVHD, and 2 of disease progression. In conclusion, our preliminary data indicate that etanercept is well tolerated and can induce a high response rate in patients with steroid-refractory aGVHD and cGVHD, particularly in the setting of GI involvement.     

Ganciclovir预防异基因造血干细胞移植后巨细胞病毒感染

目的 :评价Ganciclovir在异基因造血干细胞移植 (allo HSCT)后预防巨细胞病毒 (CMV)感染的效果。方法 :观察allo HSCT患者 46例 ,全部病例均系移植前受者和 (或 )供者的CMV IgG阳性 ,分为预防组 2 4例 ,对照组 2 2例。allo HSCT后当患者血中性粒细胞 >1.0× 10 9/L时 ,预防组开始用GCV 10mg·kg-1·d-1,分两次静滴 ,连续 5d ;然后改为 5mg·kg-1·d-1,每周用 5d ,直至 +10 0d。对照组未预防性使用GCV。结果 :在 +10 0d内 ,预防组和对照组的CMV感染率分别为 8% (2 / 2 4)、32 % (7/ 2 2 ) ,P <0 .0 5 ;CMV病发病率分别为 0 %、18% (4 / 2 2 ) ,P <0 .0 5。两组患者在 +10 0d和 +180d内的死亡率分别为 4% (1/ 2 4)和 5 % (1/ 2 2 ) ,P >0 .0 5 ;12 .5 % (3/ 2 4)和 9% (2 / 2 2 ) ,P >0 .0 5。预防组的死因分别为并发细菌和真菌感染、CMV间质性肺炎或原发病复发 ;对照组的死因均是CMV间质性肺炎。结论 :allo HSCT后预防性使用GCV能明显抑制CMV感染 ,减少CMV病发病率。GCV的主要毒副作用是导致中性粒细胞减少 ,使患者继发感染甚至死亡的机率增加。GCV预防性使用的最佳剂量、用药方案及持续时间均有待进一步探讨