Project description:<p>Allogeneic hematopoietic cell transplantation (HCT) is the only known curative option for many hematologic disorders. After transplantation, many patients develop immune mediated disorders that may be life-threatening. Post-HCT immune mediated disorders are rare relative to other diseases but the prototype of graft versus host disease (GVHD) develops in 30-70% of patients. The morbidity and mortality associated with these HCT-associated immune mediated disorders are major barriers to successful use of transplantation to cure rare hematologic malignancies such as leukemia, lymphoma, multiple myeloma, myelodysplastic/myeloproliferative syndromes amongst other diseases.</p> <p>The purpose of this study is to characterize and more completely define the onset and course of immune mediated disorders after allogeneic HCT, focusing on participants who develop cutaneous sclerosis, bronchiolitis obliterans syndrome (BOS), late acute graft-vs.-host disease (GVHD), and chronic GVHD. <ul> <li>Of the participants undergoing allogeneic hematopoietic cell transplantation (HCT), can we, the researchers better identify who will develop immune-mediated disorders, what types of disorders participants will have, and whether these disorders will be severe or respond to currently available therapies?</li> </ul> </p> <p>This is a longitudinal study of 1118 individuals (1081 adults and 100 children). Those participating in this study will be evaluated over a 3 year period at 9 study sites. Participants will be enrolled pre-transplant, or up to day 121 post transplantation. This wide enrollment window will allow sites to use recruitment methods that are most efficient at their institutions. At least 2 years of follow-up will ensure an adequate sample size, and sufficient time for observation of the full spectrum of immune mediated disorders. The data of 1023 individuals have been submitted to dbGaP.</p>
Project description:Longitudinal Study of Immune Mediated Disorders after Allogeneic HCT Protocol (Immune Mediated Disorders after Allo-HCT) - cGVHD 6501
Project description:We performed peripheral blood gene expression profiling to identify an array of transcriptional biomarkers that discriminate presence of active cGvHD requiring immunosuppression following allogeneic HCT. Peripheral blood mononuclear cells were prepared by Ficoll gradient and cryopreserved from 63 patients (median age 50 yrs; range 19-64) following allogeneic HCT (median 475 days post-HCT) on an IRB approved protocol. Samples were randomly selected into a training set (23 cGvHD and 19 without cGvHD) and test set (12 cGvHD and 9 without cGvHD) and processed on the Aligent whole human genome 44k microarray platform. Bioinformatics programs including AILUN, GeneSpring, SAM, and PAM were used to select a minimum gene-set (FDR <5%) to predict cGvHD in the training set. Patient characteristics in the two groups were collected for confounder/interaction analysis across the following parameters: age, gender, disease histology, disease status at HCT, graft source, conditioning regimen, white blood count (WBC) at sample, and follow-up status including relapse and survival. Type, grade, and activity of acute cGvHD and cGvHD at time of sample and at most recent follow-up were determined by two independent investigators by standard clinical criteria. Three-condition experiment, 35 cGvHD vs. 28 non-cGvHD samples vs. 7 controls (cGvHDnoIS; no immunosuppression drug).
Project description:Using a quantitative proteomics approach, we compared pooled plasma samples from 35 patients with cGVHD obtained at a median of 103 days post-HCT and 18 patients without cGVHD obtained at matched timepoints to identify biomarkers for cGVHD.
Project description:We performed peripheral blood gene expression profiling to identify an array of transcriptional biomarkers that discriminate presence of active cGvHD requiring immunosuppression following allogeneic HCT. Peripheral blood mononuclear cells were prepared by Ficoll gradient and cryopreserved from 63 patients (median age 50 yrs; range 19-64) following allogeneic HCT (median 475 days post-HCT) on an IRB approved protocol. Samples were randomly selected into a training set (23 cGvHD and 19 without cGvHD) and test set (12 cGvHD and 9 without cGvHD) and processed on the Aligent whole human genome 44k microarray platform. Bioinformatics programs including AILUN, GeneSpring, SAM, and PAM were used to select a minimum gene-set (FDR <5%) to predict cGvHD in the training set. Patient characteristics in the two groups were collected for confounder/interaction analysis across the following parameters: age, gender, disease histology, disease status at HCT, graft source, conditioning regimen, white blood count (WBC) at sample, and follow-up status including relapse and survival. Type, grade, and activity of acute cGvHD and cGvHD at time of sample and at most recent follow-up were determined by two independent investigators by standard clinical criteria.
Project description:UCRs expression signature of HCT-116 cell lines versus HCT-116 cell line treated with DNA methylation inhibitor 5-aza-2'-deoxycytidine