CD26 expression on donor harvest as a risk predictive biomarker for developing Graft-versus-Host Disease post-Allogeneic Hematopoietic Stem Cell Transplantation: A tenyear followup study

2021 ◽  
pp. 1-12
Author(s):  
Sachin Punatar ◽  
Shruti Kandekar ◽  
Navin Khattry ◽  
Anant Gokarn ◽  
Kumar Prabhash ◽  
...  

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (ASCT) is the preferred treatment option for patients with several hematologic disorders and immunodeficiency syndromes. Graft versus host disease (GVHD) is an immune mediated post-transplant complication which has a major impact on long term transplant outcomes. OBJECTIVE: Current efforts are focused on identification of new markers that serve as potential predictors of GVHD and other post-transplant clinical outcomes. METHODS: This study includes donor harvests collected from twenty-three allogeneic donors during period 2008–2009 and respective transplant recipients followed for clinical outcomes till March 2019. Percent CD26+ and CD34+ cells in donor harvest were analyzed using flow cytometry. Percent expression and infused dose of CD26+ and CD34+ cells were evaluated for association with various clinical outcomes. RESULTS: Total 23 healthy donors 28 years (13 males), and transplant recipients with median age 24 years (17 males) formed the study cohort. The diagnosis included malignant (n= 13) and non-malignant (n= 10) disorders. Median CD34brCD45lo HSC expression was 057% (IQR 024–103) while median CD26 expression was 1964% (IQR 896–3356) of all nucleated cells. CD26 expression was associated with donor age (P= 0.37). CD26 percent expression correlated with WBC engraftment (P= 0.015) and with acute GVHD (P= 0.023) whereas infused CD26 cell dose correlated with WBC engraftment (P= 0.004) and risk of CMV reactivation (P= 0.020). There was no statistically significant correlation of either CD26 expression or cell dose with chronic GVHD, EFS or OS.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2908-2908
Author(s):  
Sukjoong Oh ◽  
Young Ju Lee ◽  
Soo Mee Kwon ◽  
Eunkyung Park ◽  
Sungbum Cho ◽  
...  

Abstract Chronic graft-versus-host disease (GVHD) is one of the most serious long-term complications following allogeneic hematopoietic stem cell transplantation. The pathophysiology of chronic GVHD is poorly understood. Certain genes may affect the outcome by modulating tissue injury with the alloimmune reaction. We assessed the gene profiles of 21 transplant recipients with oligonucleotide microarray (CodeLink®) containing 20,142 probes. All patients received hematopoietic stem cells from HLA-matched sibling donors except one who’s HLA was mismatched in one A locus. All patients were in complete remission and in complete chimerism state. Among the 21 patients, 11 had chronic GVHD and 10 not. RNAs were extracted from peripheral blood mononuclear cells of the transplant recipients. Sample-wise hierarchical clustering of the whole gene expression profile showed tendency of GVHD patients aggregating in the dendrogram. In GVHD patients, 141 genes were revealed up-regulated by SAM method. Gene ontology annotation of these genes indicated that up-regulated genes were related with proteolysis, lipid biosynthesis, phosphate metabolism and tissue development. A total of 461 pathways were examined to find the pathways showing differential expression patterns between GVHD and non-GVHD patients. The results showed that 227 pathways were statistically significant. These pathways included many immune-related processes, including T cell receptor signaling pathway, T helper cell surface molecules pathway, and HIV induced T cell apoptosis. With the 17 selected classifier genes, prediction accuracy of PAM algorithm was 86%. We could identify differentially expressed genes and pathways in chronic GVHD patients using oligonucleotide microarrays. We also found that extracted classifier genes showed relatively high prediction accuracy. Gene expression profile data may provide new insights into biological mechanism underlying GVHD and reveal disease-associated biomarkers of potential therapeutic targets.


2019 ◽  
Vol 65 (3) ◽  
pp. 330-336
Author(s):  
Irina Gribkova ◽  
I. Ishmatova ◽  
Mariya Davydovskaya ◽  
K. Kokushkin

The aim of the study was to systematize and summarize the current available data on ruxolitinib use in patients with myelofibrosis (MF) prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) to improve its results. The review includes data from foreign and domestic articles found in the PubMed and elibrary.ru databases describing the results of the use of ruxolitinib in patients with MF prior to allo-HSCT, including clinical cases, original scientific studies and reviews. It is reported that ruxolitinib therapy is safe, reduces mortality in the early post-transplantation period, reduces the incidence of acute and chronic graft-versus-host disease, and decreases the frequency of relapses. Clinical improvement with ruxolitinib therapy prior to allo-HSCT can be considered a prognostically favorable factor.


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