scholarly journals Confounding Factors Affecting the National Institutes of Health (NIH) Chronic GVHD Organ-Specific Score and Global Severity

2014 ◽  
Vol 20 (2) ◽  
pp. S265-S266 ◽  
Author(s):  
Sahika Zeynep Aki ◽  
Yoshihiro Inamoto ◽  
Barry E. Storer ◽  
Paul A. Carpenter ◽  
Stephanie J. Lee ◽  
...  
Keyword(s):  
Chronic Gvhd ◽  
National Institutes Of Health ◽  
Confounding Factors ◽  
Factors Affecting ◽  
Organ Specific ◽  
Specific Score

scholarly journals Global and organ-specific chronic graft-versus-host disease severity according to the 2005 NIH Consensus Criteria

Blood ◽  
2011 ◽  
Vol 118 (15) ◽  
pp. 4242-4249 ◽  
Author(s):  
Sally Arai ◽  
Madan Jagasia ◽  
Barry Storer ◽  
Xiaoyu Chai ◽  
Joseph Pidala ◽  
...  
Keyword(s):  
Chronic Gvhd ◽  
Good Prognosis ◽  
Development Project ◽  
Consensus Conference ◽  
National Institutes Of Health ◽  
Severity Scores ◽  
Organ Specific ◽  
Nih Consensus Criteria ◽  
New Criteria ◽  
Conventional Risk Factors

Abstract In 2005, the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic GVHD proposed a new scoring system for individual organs and an algorithm for calculating global severity (mild, moderate, severe). The Chronic GVHD Consortium was established to test these new criteria. This report includes the first 298 adult patients enrolled at 5 centers of the Consortium. Patients were assessed every 3-6 months using standardized forms recommended by the Consensus Conference. At the time of study enrollment, global chronic GVHD severity was mild in 10% (n = 32), moderate in 59% (n = 175), and severe in 31% (n = 91). Skin, lung, or eye scores determined the global severity score in the majority of cases, with the other 5 organs determining 16% of the global severity scores. Conventional risk factors predictive for onset of chronic GVHD and nonrelapse mortality in people with chronic GVHD were not associated with NIH global severity scores. Global severity scores at enrollment were associated with nonrelapse mortality (P < .0001) and survival (P < .0001); 2-year overall survival was 62% (severe), 86% (moderate), and 97% (mild). Patients with mild chronic GVHD have a good prognosis, while patients with severe chronic GVHD have a poor prognosis. This study was registered at www.clinicaltrials.gov as no. NCT00637689.

scholarly journals Predictors of neutralizing antibody response to BNT162b2 vaccination in allogeneic hematopoietic stem cell transplant recipients

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Lorenzo Canti ◽  
Stéphanie Humblet-Baron ◽  
Isabelle Desombere ◽  
Julika Neumann ◽  
Pieter Pannus ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Chronic Gvhd ◽  
Neutralizing Antibody ◽  
Healthy Adults ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Factors Affecting

Abstract Background Factors affecting response to SARS-CoV-2 mRNA vaccine in allogeneic hematopoietic stem cell transplantation (allo-HCT) recipients remain to be elucidated. Methods Forty allo-HCT recipients were included in a study of immunization with BNT162b2 mRNA vaccine at days 0 and 21. Binding antibodies (Ab) to SARS-CoV-2 receptor binding domain (RBD) were assessed at days 0, 21, 28, and 49 while neutralizing Ab against SARS-CoV-2 wild type (NT50) were assessed at days 0 and 49. Results observed in allo-HCT patients were compared to those obtained in 40 healthy adults naive of SARS-CoV-2 infection. Flow cytometry analysis of peripheral blood cells was performed before vaccination to identify potential predictors of Ab responses. Results Three patients had detectable anti-RBD Ab before vaccination. Among the 37 SARS-CoV-2 naive patients, 20 (54%) and 32 (86%) patients had detectable anti-RBD Ab 21 days and 49 days postvaccination. Comparing anti-RBD Ab levels in allo-HCT recipients and healthy adults, we observed significantly lower anti-RBD Ab levels in allo-HCT recipients at days 21, 28 and 49. Further, 49% of allo-HCT patients versus 88% of healthy adults had detectable NT50 Ab at day 49 while allo-HCT recipients had significantly lower NT50 Ab titers than healthy adults (P = 0.0004). Ongoing moderate/severe chronic GVHD (P < 0.01) as well as rituximab administration in the year prior to vaccination (P < 0.05) correlated with low anti-RBD and NT50 Ab titers at 49 days after the first vaccination in multivariate analyses. Compared to healthy adults, allo-HCT patients without chronic GVHD or rituximab therapy had comparable anti-RBD Ab levels and NT50 Ab titers at day 49. Flow cytometry analyses before vaccination indicated that Ab responses in allo-HCT patients were strongly correlated with the number of memory B cells and of naive CD4+ T cells (r > 0.5, P < 0.01) and more weakly with the number of follicular helper T cells (r = 0.4, P = 0.01). Conclusions Chronic GVHD and rituximab administration in allo-HCT recipients are associated with reduced Ab responses to BNT162b2 vaccination. Immunological markers could help identify allo-HCT patients at risk of poor Ab response to mRNA vaccination. Trial registration The study was registered at clinicaltrialsregister.eu on 11 March 2021 (EudractCT # 2021-000673-83).

scholarly journals Efficacy of folinic acid rescue following MTX GVHD prophylaxis: results of a double-blind, randomized, controlled study

2020 ◽  
Vol 4 (16) ◽  
pp. 3822-3828
Author(s):  
Moshe Yeshurun ◽  
Uri Rozovski ◽  
Oren Pasvolsky ◽  
Ofir Wolach ◽  
Ron Ram ◽  
...  
Keyword(s):  
Folinic Acid ◽  
Oral Mucositis ◽  
Hematopoietic Cell Transplantation ◽  
Controlled Trial ◽  
Chronic Gvhd ◽  
Controlled Study ◽  
Double Blind ◽  
Randomized Controlled ◽  
Gvhd Prophylaxis ◽  
Organ Specific

Abstract The use of methotrexate (MTX) for graft-versus-host disease (GVHD) prophylaxis is associated with increased rates of organ-specific toxicities. Despite limited data, the European Society for Blood and Marrow Transplantation-European LeukemiaNet working group recommend the use of folinic acid (FA) rescue to reduce MTX toxicity after allogeneic hematopoietic cell transplantation (allo-HCT). In a multicenter, double-blind, randomized, controlled trial, we explored whether FA rescue reduces MTX-induced toxicity. We enrolled patients undergoing allo-HCT with myeloablative conditioning with peripheral blood stem cell grafts, with GVHD prophylaxis consisting of cyclosporine and MTX. Patients were randomized to receive FA or placebo starting 24 hours after each MTX dose and continuing over 24 hours in 3 to 4 divided doses. The primary end point was the rate of grades 3 and 4 oral mucositis. After enrollment of 52 patients (FA, n = 28; placebo, n = 24), preplanned interim analysis revealed similar rates of grade 3 and 4 (46.6% vs 45.8%; P = .97) and grades 1 to 4 (83.3% vs 77.8%; P = .65) oral mucositis. With a median follow-up of 17 (range, 4.5-50) months, there was no difference in the rates of acute and chronic GVHD, disease relapse, nonrelapse mortality, and overall survival. These interim results did not support continuation of the study. We conclude that FA rescue after MTX GVHD prophylaxis does not decrease regimen-related toxicity or affect transplantation outcomes. This study was registered at clinicaltrials.gov as #NCT02506231.

scholarly journals Confounding factors affecting the marginal quality of an intra-oral scan

2017 ◽  
Vol 59 ◽  
pp. 33-40 ◽  
Author(s):  
Andrew Keeling ◽  
Jinhua Wu ◽  
Marco Ferrari
Keyword(s):  
Confounding Factors ◽  
Factors Affecting

scholarly journals Refined National Institutes of Health response algorithm for chronic graft-versus-host disease in joints and fascia

2020 ◽  
Vol 4 (1) ◽  
pp. 40-46
Author(s):  
Yoshihiro Inamoto ◽  
Stephanie J. Lee ◽  
Lynn E. Onstad ◽  
Mary E. D. Flowers ◽  
Betty K. Hamilton ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Therapeutic Response ◽  
Chronic Gvhd ◽  
National Institutes Of Health ◽  
Host Disease ◽  
Graft Versus Host ◽  
Health Response ◽  
Key Points ◽  
Total P

Key Points The NIH joint/fascia score and total P-ROM score should be used for assessing therapeutic response in joint/fascia chronic GVHD. A change from 0 to 1 on the NIH joint/fascia score should not be considered as worsening.

ASBMT Risk Group and CD 34+ Dose Predicted for the Development of aGVHD in Allogeneic MRD Transplants When the Donors Who Received a Combined Mobilization and In Vivo TCD Regimen Using rhg-CFS and Dexamethasone.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5006-5006
Author(s):  
Khaleel K. Ashraf ◽  
Arabella B. Tilden ◽  
Yufeng Li ◽  
Sameer Gupta ◽  
Lawrence S. Lamb ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Risk Factor ◽  
Median Survival ◽  
Chronic Gvhd ◽  
Multivariable Analysis ◽  
Multivariable Logistic Regression Analysis ◽  
Factors Affecting ◽  
Cd 34 ◽  
The Relationship

Abstract We looked at factors affecting the development of acute and chronic GVHD in a cohort of 118 patients who underwent allogeneic matched sibling transplantation between 09/1998 to 05/2006 at the UAB BMT program. Donors were mobilized with rhg-CSF (10–16mcg/kg/day x4) and received dexamethasone 10mg/m2/day x3 days to effect in vivo T cell depletion (TCD). Total CD3 and CD34 cell dose were divided in to 4 quartiles (See table below). We then analyzed the influence of CD3+ and CD34+ dose quartiles on aGVHD, cGVHD, engraftment, TRM and relapse. (see table) Acute GVHD: Univariate Logistic regression indicated that the development of aGVHD is negatively associated with quartiles (q25–q50) interval of CD3 dose (p=0.0418). However this relationship was not independent of risk factor and CD34 dose. After using Multivariable Logistic regression analysis with adjustments for age, race and sex, we found that ASBMT risk factor and CD34 quartiles dose are strong predictors of aGVHD: patients who had high risk are about three times more likely to have aGVHD (OR=2.829, 95% CI 1.142–7.020, p=0.0250). The higher the CD34 dose also predisposed to higher incidence of aGVHD (p=0.0432). Median Survival: Patients who received the CD3 (P=0.00141) and CD34 (P=0.0270) in the q25–q50 quartile did better with improved median survival. Relapse and CD 3 quartiles: Using the - 2 log (LR) test shows the relapse free interval was longer if the CD3 dose is between q25 and q50 (p=0.0058); there was no relation between CD34 and relapse. TRM: Not associated with CD3 or CD 34 dose. WBC engraftment: Multivariable analysis indicated that the relationship is mainly an age effect. After adjusted for risk factor, GVHD status, CD3 or CD34 dose, the engraftment day is still significantly related to age at BMT (p=0.0252). No associations are observed for the relationship between engraftment day and GVHD risk. cGVHD: Neither CD34 dose (p=0.5339) nor CD3 (p=0.4209) dose were statistically associated with incidence and severity of cGVHD. To summarize, higher CD34 dose and higher risk ASBMT category predicted for higher incidence of aGVHD; neither CD3 nor CD 34 dose predicted for the development of cGVHD. Age was the single most important predictor of WBC engraftment. CD3+ and CD34 Quartiles Quartile <25 25–50 50–75 >75 CD3 X10E8 <2.5 2.53–3.60 3.60–5.30 >5.30 CD34 X10E6 <4.92 4.92–7.79 7.79–11.2 >11.2

The Risk of Organ Specific Graft-Versus-Host Disease Can Be Predicted by the Multiple Single Nucleotide Polymorphism Based Predictive Models.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3056-3056
Author(s):  
Dennis Dong Hwan Kim ◽  
Hong-Hee Won ◽  
Wei Xu ◽  
Jieun Uhm ◽  
Vikas Gupta ◽  
...  
Keyword(s):  
Predictive Models ◽  
Genetic Factors ◽  
Acute Gvhd ◽  
Multivariate Analyses ◽  
Chronic Gvhd ◽  
Snp Markers ◽  
Clinical Factors ◽  
Single Nucleotide ◽  
Graft Versus Host ◽  
Organ Specific

Abstract Abstract 3056 Background: The pathogenesis of GVHD is not fully understood. Alloreactive T-lymphocytes are believed to be key mediators of GVHD. However, it is not clear if the pathobiology of GHVD is similar in each target organ GVHD. We aimed to identify predictive single nucleotide polymorphisms (SNP) markers associated with the risk of acute or chronic graft versus host disease (GVHD) as well as organ specific GVHD in 394 transplant recipients and donors. Methods: A total of 259 SNPs were genotyped in 53 genes, and evaluated for the risk of acute/chronic GVHD and organ specific GVHD. Predictive models were generated using both clinical factors and genetic SNP markers confirmed by multivariate analyses. Patients were stratified by quartile (25%) according to their risk score, and the risk of overall and organ specific GVHD were compared among the 3 risk groups (low, intermediate and high risk). C-statistic analysis was also performed to compare the stratification power of the predictive model generated using clinical and genetic factors with a model obtained using only clinical factors. Results: Several SNP markers in the cytokine-, apoptosis-, TGF-¥â or PDGF-mediated pathways were identified as predictive markers of acute/chronic GVHD. The risk of acute GVHD was associated with clinical factors such as HLA disparity and patient age. In addition, recipient FAS genotype (rs2234978), EDN1 genotype (rs4714384), and TGFB genotype (rs1800469), and donor TNFRII genotype (rs3397) were also strong predictive markers for acute GVHD. Significant predictive risk factors forchronic GVHD were the source of stem cells, a previous episode of acute GVHD and the donor IL1R1 genotype (rs3917225). Each organ specific GVHD shared common biologic pathways such as cytokine, TGF-¥â or PDGF-mediated pathways. However, different SNP markers were identified as predictive for individual organ-specific GVHD. Multivariate analyses identified several SNP markers may predict the risk of organ specific acute GVHD in combination with clinical factors. For skin acute GVHD, recipient PDGFD (rs10895534), donor NOS2A (rs3730017), TNFRII (rs3397) and TGFB1 (rs1800469) genotypes were predictive together with clinical factors such as HLA disparity. Donor's genotype for TNFRII (rs3397) was predictive not only for overall acute GVHD but also for skin acute GVHD. No clinical factors were identified for the risk of liver or gut acute GVHD, but several SNP markers were found including recipient PDGFRB (rs2302273), IFNGR1 (rs2234711) and donor PTGS1 (rs10306114), NOS1 (rs9658254), IL1R1 (rs2192752) genotypes for liver acute GVHD and recipient IL4 (rs2243248), donor PDGFD (rs1053861), TGFBR1 (rs420549), IL12A (rs2243115) genotypes for gut acute GVHD. In summary, there are no overlapping SNP markers for the risk prediction of organ specific acute GVHD. For organ specific chronic GVHD, 2 clinical risk factors were predictive including source of stem cells and a preceding history of acute GVHD. In addition, several SNP markers were also identified: recipient PDGFC (rs1425486), donor NFKB1 (rs1805034) and NOS2A (rs3730017) for skin chronic GVHD; recipient IL10RB (rs8178561) and PDGFRB (rs22229562), and donor TGFBR1 (rs868) for eye chronic GVHD; recipient IL12RB1 (rs3746190) and donor FCGR2A (rs1801274) for oral chronic GVHD; and donor IL4R (rs2057768), FAS (rs2234767) and TGFB1 (rs1800469) for lung chronic GVHD. Again, In no overlapping SNP markers were observed for organ-specific chronic GVHD risk. Although this predictive model could not stratify patients according to their risk of overall chronic GVHD (p=0.0763), the predictive models per each organ specific chronic GVHD enabled to stratify the patients according to their risks of each organ specific GVHD (p<0.0001 for skin chronic GVHD, p=0.0033 for eye chronic GVHD, p=0.003 for oral chronic GVHD and p=0.0036 for lung chronic GVHD).Predictive models incorporating clinical and genetic factors improved the stratification power by 11.1% compared to models only including clinical factors. Conclusion: Our study suggests that SNP based approaches can predict the risk of organ-specific GVHD. These SNP markers need to be validated in other series. These SNPs may help focus studies into pathobiology and targeted therapy of GVHD in the future. Disclosures: No relevant conflicts of interest to declare.

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