Comparison of the meibomian gland dysfunction in patients with chronic ocular graft-versus-host disease and Sjogren's syndrome

AIM: To investigate the abnormalities in the meibomian gland in patients with dry eye disease(DED) associated with chronic ocular graft-versus-host disease(coGVHD) in comparison with Sj?gren's syndrome(SS), a major form of aqueous deficient DED and meibomian gland dysfunction(MGD), a common cause of evaporative DED.METHODS: A total 135 eyes of 135 subjects included in this study: patients with DED associated with coGVHD(n=30), patients with SS(n=35), patients with MGD(n=35), and normal controls(n=35). All participants completed the Ocular Surface Disease Index(OSDI) questionnaire, ocular surface examination [Schirmer test, tear film breakup time(TFBUT), and ocular surface staining], and meibomian gland assessment [meiboscore(gland dropout detected on meibography using infrared camera of the Keratograph 5 M), meibum expressibility score(MES), meibum quality score(MQS), lid margin abnormality]. In addition, correlations of meibomian gland characteristics with ocular surface parameters as well as disease severity score were investigated in coGVHD group.RESULTS: The coGVHD group showed significantly higher meiboscore, MES, and MQS than the other 3 groups(all P<0.05). In the coGVHD group, parameters of meibomian gland showed a significant correlation each other and those of ocular surface. The correlation between meibomian gland parameters and severity score of co GVHD was also established(meiboscore, r=0.62; MES, r=0.47; MQS, r=0.47; lid margin abnormality score, r=0.55; all P<0.05).CONCLUSION: Patients with DED associated with co GVHD show poorer gland morphology and worse glandfunction than other types of DED. In addition, meibomian gland damage is not only associated with ocular surface damage but also disease severity of coGVHD.

Health related quality of life among patients with chronic graft-versus-host disease in China

Background Chronic graft-versus-host disease （GVHD）,the commonest long-term complication after allogeneic hematopoietic stem cell transplantation （HSCT）,has a negative impact on patients＇ health related quality of life （HRQoL）.This study was designed to investigate the HRQoL in patients with chronic GVHD in China.Methods Two hundred and sixty-four patients with chronic GVHD who were ＞24 months post-HSCT and had been in continuous complete remission since HSCT were enrolled in this retrospective study.HRQoL was evaluated using an SF-36 questionnaire.Multivariate analysis was used to identify the factors that affect HRQoL in patients with chronic GVHD.Results HRQoL in patients categorized as having mild and moderate chronic GVHD was significantly better than in those in the severe category.In the moderate chronic GVHD category,markedly poorer HRQoL was observed in patients with both multiple organ involvement and more severe organ impairment than in those without these factors.According to multivariate analysis,chronic GVHD severity had the greatest significant negative impact on patients＇ HRQoL; whereas being female was associated with a negative impact on psychological health.Conclusion Chronic GVHD severity strongly correlates with negative impacts on patients＇ HRQoL.

Potential value of autoantibodies as biomarkers of chronic graft-versus-host disease after allogeneic stem cell transplantation

We investigated the value of autoantibodies as biomarkers of chronic graft-versus-host disease(cGVHD)by analyzing the autoantibody profiles of 65 patients(34 cGVHD and 31 non-cGVHD)surviving longer than three months after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Autoantibodies to at least one antigen were detected in 45 patients(70.8%),with multiple autoantibodies detected in 30 patients(46.2%).Antinuclear antibodies(ANAs)were the most frequently detected autoantibodies,with a significantly higher prevalence in non-cGVHD patients and c GVHD patients than that in healthy controls(HCs).ANA-nucleolar(ANA-N)was the main immunofluorescence pattern of ANA-positivity in both the non-cGVHD and c GVHD groups.There was a higher prevalence of anti-Ro52-positivity in non-cGVHD and cGVHD patients than in HC.Liver cGVHD was significantly associated with anti-Ro52-positivity.However,cGVHD activity and severity were not associated with the presence of autoantibodies.Similarly,there were no significant differences in overall survival or relapse among the four groups of patients expressing autoantibodies.Our results suggest that autoantibodies have limited value in predicting cGVHD.

Risk factors for chronic graft-versus-host disease after anti-thymocyte globulin-based haploidentical hematopoietic stem cell transplantation in acute myeloid leukemia

Chronic graft-versus-host disease(cGVHD)is a major complication following unmanipulated haploidentical hematopoietic stem cell transplantation(haplo-HSCT).We aimed to identify the risk factors for cGVHD in patients who underwent anti-thymocyte globulin-based haplo-HSCT for acute myeloid leukemia(n=280).The diagnosis of cGVHD was in accordance with the National Institutes of Health consensus criteria.A total of 169 patients suffered from cGVHD.The patients who had 3 loci mismatched had a higher 8-year incidence of cGVHD(total,66.0%vs.53.7%,P=0.031;moderate to severe,42.4%vs.30.1%,P=0.036)than the patients who had 1 to 2 loci mismatched.The patients who had maternal donors had a higher 8-year incidence of moderate to severe cGVHD(49.2%vs.32.9%,P=0.024)compared with the patients who had other donors.The patients who had grades III to IV acute GVHD(aGVHD)had higher 8-year incidence of cGVHD(total,88.0%vs.50.4%,P<0.001;moderate to severe,68.0%vs.27.0%,P<0.001)compared with the patients without aGVHD.In multivariate analysis,grades III to IV aGVHD was the only independent risk factor for cGVHD.Thus,further interventions should be considered in patients with severe aGVHD to prevent cGVHD.

PLACENTAL INTRAVENOUS IMMUNOGLOBULIN (PtIVIG) FOR TREATMENT OF CHRONIC GRAFT VERSUS HOST DISEASE (CGVHD)

Plasma immunoglobulin has been used widely in clinic for the prophylaxis and treatment of infections in patients after bone marrow transplantation(BMT).However,there are no hard data demonstrating that it can act against GVHD,

Artesunate attenuate chronic graft-versushost disease by regulating Th17/Treg balance

Objective To investigate the effects of artesunatetreatment on chronic graft-versus-host disease(cGVHD). Methods Recipient BALB /c mice received8 × 106 bone marrow cells with 8 × 106 spleen cells fromB10D2 mice. Artesunate solubilized in acetone was injectedintraperitoneally every day at a dose of 1 mg /kg onDay 28 after BMT. The clinical scores,survival and histopathologicaldamage were analyzed. The frequency ofTh17 and Tregs in PB and spleens from the mice wereevaluated by flow cytometry. In addition,CD4 + T cellsfrom the spleens of mice were cultured in vitro,thenstimulated with artesunate,the frequency of Th17 andTregs in these splenocytes were evaluated by flow cytometry.

一种实用性狼疮样肾炎动物模型──鼠慢性移植物抗宿主病的制备

目的建立一种狼疮样肾炎动物模型，为人类狼疮性肾炎（ＬＮ）实验和临床研究提供基础。方法取雌性亲代ＤＢＡ／２的淋巴细胞分４次经静脉注射雌性子代Ｆ１代杂交鼠（Ｃ５７ＢＬ６× ＤＢＡ２）。注射时间为０，３，７，１０ ｄ。每次注射淋巴细胞数为５０× １０６。结果尿白蛋白于第４次注射后２周开始升高，第１２周达高峰；血抗ｄｓ－ＤＮＡ水平于第４次注射后２周已明显升高，至第４周达高峰，各时点与对照组差异明显。普通光镜（ＰＡＳ、ＰＡＳＭ）示肾小球基底膜增厚，系膜轻度增生，小管间质炎症细胞浸润；免疫荧光示ＩｇＧ沿基底膜呈线状或颗粒状沉积，部分小管基底膜亦可见其沉积；电镜显示膜性肾炎改变，基底膜增宽，内有电子致密物沉积，上皮细胞足交融合。结论本实验所建立狼疮样肾炎动物模型，主要为膜性肾炎。

慢性移植物抗宿主病狼疮样小鼠模型的诱导

目的 诱导慢性移植物抗宿主病狼疮样小鼠模型。方法 选用 (DBA 2×C57BL 6J)F1小鼠 ,通过尾静脉注射其母鼠DBA 2淋巴细胞诱导模型 ,观察 12周。结果 F1小鼠注射母鼠淋巴细胞后 2周产生自身抗体 ,出现蛋白尿 ,4周血脂、血肌酐、尿素氮轻度升高 ,肾脏病理仅有系膜细胞轻度增生 ,未见间质损害。 8周血生化指标明显改变 ,肾脏病理示肾小球系膜细胞中度增生 ,间质炎细胞浸润和肾小管大量蛋白管型 ,10～ 12周各项观察指标改变明显 ,病理出现局灶或弥漫肾小球硬化 ,免疫荧光示IgG、IgM、C3沿毛细血管壁及系膜区沉积。结论 慢性移植物抗宿主病狼疮样小鼠模型类似人类狼疮性肾炎 。

IL-2调控免疫耐受及其在慢性移植物抗宿主病治疗中的应用研究

慢性移植物抗宿主病(c GVHD)是异基因造血干细胞移植术后常见的并发症,该病与移植后供体来源T细胞和B细胞激活的一系列免疫反应及免疫耐受缺失有关。白介素-2(IL-2)是维持具有免疫调节功能的CD4+Foxp3+调节性T细胞分化、存活及其功能的关键因子。本文综述IL-2通过特异性增加调节性T细胞数量从而增强其免疫抑制功能的相关研究,以及重建移植后T细胞稳态在c GVHD预防和治疗中的研究进展。

Optimizing antithymocyte globulin dosing in haploidentical hematopoietic cell transplantation:long-term follow-up of a multicenter,randomized controlled trial

Given that randomized studies testing the long-term impact of antithymocyte globulin(ATG)dosing are scarce,we report the results of an extended follow-up from the original trial.In our prospective,multicenter,randomized trial,408 leukemia patients 14–65 years of age who underwent haploidentical hematopoietic cell transplantation(haplo-HCT)under our original“Beijing Protocol”were randomly assigned one-to-one to ATG doses of 7.5 mg/kg(n=203,ATG-7.5)or 10 mg/kg(n=205,ATG-10.0)at four sites.Extended follow-up(median 1968 d(range:1300–2710 d)indicated comparable 5-year probabilities of moderate-to-severe chronic graft-versus-host disease(GVHD)(hazard ratio(HR):1.384,95%confidence interval(CI):0.876–2.189,P=0.164),nonrelapse mortality(HR:0.814,95%CI:0.526–1.261,P=0.357),relapse(HR:1.521,95%CI:0.919–2.518,P=0.103),disease-free survival(HR:1.074,95%CI:0.783–1.473,P=0.658),and GVHD-free/relapse-free survival(HR:1.186,95%CI:0.904–1.555,P=0.219)between groups(ATG-7.5 vs.ATG-10.0).The 5-year rate of late effects did not differ significantly.However,the cytomegalovirus/Epstein-Barr virus-related death rate was much higher in the ATG-10.0 cohort than in the ATG-7.5 cohort(9.8%vs.1.5%;P=0.003).In summary,patients undergoing haplo-HCT benefit from 7.5 mg/kg ATG compared to 10.0 mg/kg ATG based on a balance between GVHD and infection control.ATG(7.5 mg/kg)is potentially regarded as the standard regimen in the platform.These results support the optimization of ATG use in the“Beijing Protocol”,especially considering the potential economic advantage in developing countries.

治疗慢性移植物抗宿主病药物——belumosudil

belumosudil是一种Rho相关卷曲螺旋蛋白激酶(ROCK)抑制剂,由Kadmon制药公司开发,用于治疗慢性移植物抗宿主病(cGVHD)和系统性硬化症。2021年7月16日,belumosudil在美国首次获准上市,用于既往至少接受过2次系统一线治疗失败后的cGVHD成人患者和12岁及以上的cGVHD儿童患者。本文从药理作用及作用机制、药动学、临床疗效评价、安全性评价、用法用量等方面对belumosudil进行综述,旨在为临床合理用药提供参考。

Implications for the therapeutic role of Imatinib in systemic sclerosis: a single-arm meta-analysis

Sclerotic chronic graft-versus-host disease (ScGVHD) or systemic sclerosis (SSc) is one of the most severe manifestations of chronic graft-versus-host disease (cGVHD) since the involvement of major organs significantly affects the mortality and morbidity of SSc patients. Currently, there are no effective therapeutic approaches or standard “second-line” therapy for SSc. Imatinib, a clinical tyrosine kinase inhibitor used to treat chronic myeloid leukemia and gastrointestinal tumor, has shown potential therapeutic effects in treating ScGVHD or SSc. Due to the current limitations of clinical trials using Imatinib in the treatment of SSc, the results vary among different studies, and the applications of Imatinib in SSc is still in vagueness. Here we conducted a single-arm meta-analysis to quantitatively and systematically interpret the results of previous studies, as to evaluate the potential therapeutic effect of Imatinib in SSc. The pooled clinical response rate (CRR) showed that Imatinib had higher CRR in SSc patients with longer disease duration (CRR = 0.550) and lung involvement (CRR = 0.601) than those without (P<0.001). Therefore, it was encouraging to con duct future clinical studies regarding Imatinib therapy in SSc patients, since the global response rate of Imatinib was higher than expected in specific subgroup patients.