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.

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.

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.

造血干细胞移植后硬皮病样慢性移植物抗宿主病的临床表现

目的探讨异基因造血干细胞移植（allo-HSCT）后硬皮病样慢性移植物抗宿主病（Sc GVHD）的发病率、危险因素。方法对我院2012年1月～2014年12月之间进行allo-HSCT的259例患者发生Sc GVHD的情况进行回顾性分析。结果 134例（51.7%）发生慢性移植物抗宿主病（c GVHD）,其中22例为硬皮病型,即Sc GVHD在移植患者中的发病率为8.49%（22/259）、在c GVHD患者中的发病率为16.4%（22/134）。Sc GVHD出现的中位时间为移植后12.5（4～28）月。单因素分析结果提示预处理方案是否含全身照射（TBI）（P=0.031）、GVHD预防方案是否含霉酚酸酯（MMF）（P=0.046）、c GVHD（P=0.008）的发生、供者淋巴细胞回输（DLI）（P=0.001）均与Sc GVHD的发生具有相关性。多因素分析确定c GVHD[相对危险度（RR）=3.512,95%可信区间（CI）=1.235～9.987,P=0.018]和DLI（RR=5.217,95%CI=1.698～16.029,P=0.004）为Sc GVHD发病的独立危险因素。结论Sc GVHD是移植后一种较为少见的并发症,移植物抗宿主病（GVHD）和DLI是其发病的独立危险因素。

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.

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.