Dataset Information

National Institutes of Health-Defined Chronic Graft-vs.-Host Disease in Pediatric Hematopoietic Stem Cell Transplantation Patients Correlates With Parameters of Long-Term Immune Reconstitution.

ABSTRACT: Recent data revealed the importance of immune reconstitution (IR) for the evaluation of possible biomarkers in National Institutes of Health (NIH)-defined chronic graft-vs.-host disease (cGVHD) and its clinical aspects. In this large pediatric study (n = 146), we have analyzed whether cellular and humoral parameters of IR in the long-term follow-up (FU) with a special emphasis on B-cell reconstitution correlate with NIH-defined cGVHD criteria. HYPOTHESIS: we were especially interested in whether meaningful cGVHD biomarkers could be defined in a large pediatric cohort. We here demonstrate for the first time in a highly homogenous pediatric patient cohort that both cGVHD (n = 38) and its activity were associated with the perturbation of the B-cell compartment, including low frequencies of CD19+CD27+ memory B-cells and increased frequencies of circulating CD19+CD21low B-cells, a well-known hyperactivated B-cell subset frequently found elevated in chronic infection and autoimmunity. Notably, resolution of cGVHD correlated with expansion of CD19+CD27+ memory B-cells and normalization of CD19+CD21low B-cell frequencies. Moreover, we found that the severity of cGVHD had an impact on parameters of IR and that severe cGVHD was associated with increased CD19+CD21low B-cell frequencies. When comparing the clinical characteristics of the active and non-active cGVHD patients (in detail at time of analyses), we found a correlation between activity and a higher overall severity of cGVHD, which means that in the active cGVHD patient group were more patients with a higher disease burden of cGVHD-despite similar risk profiles for cGVHD. Our data also provide solid evidence that the time point of analysis regarding both hematopoietic stem cell transplantation (HSCT) FU and cGVHD disease activity may be of critical importance for the detailed investigation of pediatric cohorts. Finally, we have proven that the differences in risk factors and patterns of IR, with cGVHD as its main confounding factor, between malignant and non-malignant diseases, are important to be considered in future studies aiming at identification of novel biomarkers for cGVHD.

SUBMITTER: Lawitschka A

PROVIDER: S-EPMC6718560 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

National Institutes of Health-Defined Chronic Graft-vs.-Host Disease in Pediatric Hematopoietic Stem Cell Transplantation Patients Correlates With Parameters of Long-Term Immune Reconstitution.

Lawitschka Anita A Gueclue Ece Dila ED Januszko Angela A Körmöczi Ulrike U Rottal Arno A Fritsch Gerhard G Bauer Dorothea D Peters Christina C Greinix Hildegard T HT Pickl Winfried F WF Kuzmina Zoya Z

Frontiers in immunology 20190827

Recent data revealed the importance of immune reconstitution (IR) for the evaluation of possible biomarkers in National Institutes of Health (NIH)-defined chronic graft-vs.-host disease (cGVHD) and its clinical aspects. In this large pediatric study (<i>n</i> = 146), we have analyzed whether cellular and humoral parameters of IR in the long-term follow-up (FU) with a special emphasis on B-cell reconstitution correlate with NIH-defined cGVHD criteria. HYPOTHESIS: we were especially interested in ...[more]

PMID: 31507582

Similar Datasets

Project description:ImportanceRuxolitinib, a selective inhibitor of the Janus kinases 1/2 signaling pathway, has shown a significant response in steroid-refractory chronic graft-vs-host disease (SR-cGVHD), a major cause of morbidity and mortality in individuals who have undergone allogeneic hematopoietic stem cell transplantation (HSCT).ObjectivesTo investigate the clinical response to ruxolitinib in patients with SR-cGVHD after allogeneic HSCT and to evaluate its safety profile during the treatment course.Design, setting, and participantsThis single-center case series included 41 consecutive patients who were treated with ruxolitinib for SR-cGVHD after allogeneic HSCT between August 2017 and December 2019. Data were collected from each patient's medical record at the First Affiliated Hospital of Zhejiang University School of Medicine. Data analysis was conducted from March to May 2020.ExposureRuxolitinib.Main outcomes and measuresTreatment responses, factors associated with response, and adverse effects during ruxolitinib administration.FindingsOverall, 41 patients (median [range] age, 31 [17-56] years; 14 [34.1%] women) were treated with ruxolitinib and included in this study. A total of 15 patients (36.6%) had a complete remission, and 14 (34.1%) had a partial remission, with an overall response rate of 70.7% (29 patients; 95% CI, 56.2%-85.3%). Lung involvement (odds ratio, 0.112; 95% CI, 0.020-0.639; P = .01) and matched related donors (odds ratio, 0.149; 95% CI, 0.022-0.981; P = .048) were associated with less favorable treatment response. Major adverse events associated with ruxolitinib were cytopenias and infectious complications. The median (range) follow-up for this cohort was 14.9 (1.4-32.5) months. Prolonged survival was observed in patients with a male donor (P = .006), complete remission before transplantation (P = .02), baseline moderate cGVHD (P = .02), and skin cGVHD (P = .001).Conclusions and relevanceIn this small, single-site case series, ruxolitinib demonstrated a significant response in heavily pretreated patients with SR-cGVHD and a reasonably well-tolerated safety profile. The results add to the body of literature suggesting ruxolitinib as a promising treatment option in SR-cGVHD.

Project description:ImportanceCertain antibiotic exposures have been associated with increased rates of acute graft-vs-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (allo-HCT). Since antibiotic exposure can both affect and be affected by infections, analyzing time-dependent exposure in the presence of multiple potential confounders, including prior antibiotic exposures, poses specific analytical challenges, necessitating both a large sample size and unique approaches.ObjectiveTo identify antibiotics and antibiotic exposure timeframes associated with subsequent aGVHD.Design, setting, and participantsThis cohort study assessed allo-HCT at a single center from 2010 to 2021. Participants included all patients aged at least 18 years who underwent their first T-replete allo-HCT, with at least 6 months of follow-up. Data were analyzed from August 1 to December 15, 2022.ExposuresAntibiotics between 7 days before and 30 days after transplant.Main outcomes and measuresThe primary outcome was grade II to IV aGVHD. The secondary outcome was grade III to IV aGVHD. Data were analyzed using 3 orthogonal methods: conventional Cox proportional hazard regression, marginal structural models, and machine learning.ResultsA total of 2023 patients (median [range] age, 55 [18-78] years; 1153 [57%] male) were eligible. Weeks 1 and 2 after HCT were the highest-risk intervals, with multiple antibiotic exposures associated with higher rates of subsequent aGVHD. In particular, exposure to carbapenems during weeks 1 and 2 after allo-HCT was consistently associated with increased risk of aGVHD (minimum hazard ratio [HR] among models, 2.75; 95% CI, 1.77-4.28), as was week 1 after allo-HCT exposure to combinations of penicillins with a β-lactamase inhibitor (minimum HR among models, 6.55; 95% CI, 2.35-18.20).Conclusions and relevanceIn this cohort study of allo-HCT recipients, antibiotic choices and schedules in the early course of transplantation were associated with aGVHD rates. These findings should be considered in antibiotic stewardship programs.

Dataset Information

National Institutes of Health-Defined Chronic Graft-vs.-Host Disease in Pediatric Hematopoietic Stem Cell Transplantation Patients Correlates With Parameters of Long-Term Immune Reconstitution.

Publications

National Institutes of Health-Defined Chronic Graft-vs.-Host Disease in Pediatric Hematopoietic Stem Cell Transplantation Patients Correlates With Parameters of Long-Term Immune Reconstitution.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets