Browsing by Author "Jagasia, Madan"

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    The Biology of Chronic Graft-versus-Host Disease: A Task Force Report from the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease
    (Elsevier, 2017-02) Cooke, Kenneth R.; Luznik, Leo; Sarantopoulos, Stefanie; Hakim, Frances T.; Jagasia, Madan; Fowler, Daniel H.; van den Brink, Marcel R. M.; Hansen, John A.; Parkman, Robertson; Miklos, David B.; Martin, Paul J.; Paczesny, Sophie; Vogelsang, Georgia; Pavletic, Steven; Ritz, Jerome; Schultz, Kirk R.; Blazar, Bruce R.; Department of Pediatrics, School of Medicine
    Chronic graft-versus-host disease (GVHD) is the leading cause of late, nonrelapse mortality and disability in allogeneic hematopoietic cell transplantation recipients and a major obstacle to improving outcomes. The biology of chronic GVHD remains enigmatic, but understanding the underpinnings of the immunologic mechanisms responsible for the initiation and progression of disease is fundamental to developing effective prevention and treatment strategies. The goals of this task force review are as follows: • Summarize the current state of the science regarding pathogenic mechanisms of chronic GVHD and critical knowledge gaps. • Develop working hypotheses/overriding concepts for chronic GVHD development. • Define the usefulness of current preclinical models to test working hypotheses and ultimately discover and develop new therapeutic strategies. • Identify shortcomings of preclinical models, and define criteria for the creation of additional models to address these limitations. This document is intended as a review of our understanding of chronic GVHD biology and therapies resulting from preclinical studies, and as a platform for developing innovative clinical strategies to prevent and treat chronic GVHD.
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    Biomarker Panel for Chronic Graft-Versus-Host Disease
    (American Society of Clinical Oncology, 2016-08-01) Yu, Jeffrey; Storer, Barry E.; Kushekhar, Kushi; Zaid, Mohammad Abu; Zhang, Qing; Gafken, Philip R.; Ogata, Yuko; Martin, Paul J.; Flowers, Mary E.; Hansen, John A.; Arora, Mukta; Cutler, Corey; Jagasia, Madan; Pidala, Joseph; Hamilton, Betty K.; Chen, George L.; Pusic, Iskra; Lee, Stephanie J.; Paczesny, Sophie; Medicine, School of Medicine
    PURPOSE: To identify diagnostic and prognostic markers of chronic graft-versus-host disease (cGVHD), the major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). PATIENTS AND METHODS: Using a quantitative proteomics approach, we compared pooled plasma samples obtained at matched time points after HCT (median, 103 days) from 35 patients with cGVHD and 18 without cGVHD (data are available via ProteomeXchange with identifier PXD002762). Of 105 proteins showing at least a 1.25-fold difference in expression, 22 were selected on the basis of involvement in relevant pathways and enzyme-linked immunosorbent assay availability. Chemokine (C-X-C motif) ligand 9 (CXCL9) and suppression of tumorigenicity 2 (ST2) also were measured on the basis of previously determined associations with GVHD. Concentrations of the four lead biomarkers were measured at or after diagnosis in plasma from two independent verification cohorts (n = 391) to determine their association with cGVHD. Their prognostic ability when measured at approximately day +100 after HCT was evaluated in plasma of a second verification cohort (n = 172). RESULTS: Of 24 proteins measured in the first verification cohort, nine proteins were associated with cGVHD, and only four (ST2, CXCL9, matrix metalloproteinase 3, and osteopontin) were necessary to compose a four-biomarker panel with an area under the receiver operating characteristic curve (AUC) of 0.89 and significant correlation with cGVHD diagnosis, cGVHD severity, and nonrelapse mortality. In a second verification cohort, this panel distinguished patients with cGVHD (AUC, 0.75), and finally, the panel measured at day +100 could predict cGVHD occurring within the next 3 months with an AUC of 0.67 and 0.79 without and with known clinical risk factors, respectively. CONCLUSION: We conclude that the biomarker panel measured at diagnosis or day +100 after HCT may allow patient stratification according to risk of cGVHD.
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    Early Th1 immunity promotes immune tolerance and may impair graft-versus-leukemia effect after allogeneic hematopoietic cell transplantation
    (European Hematology Association, 2016-05) Engelhardt, Brian G.; Paczesny, Sophie; Jung, Dae Kwang; Daguindau, Etienne; Jagasia, Madan; Savani, Bipin N.; Chinratanalab, Wichai; Cornell, Robert F.; Goodman, Stacey; Greer, John P.; Kassim, Adetola A.; Sengsayadeth, Salyka; Yoder, Sandra M.; Rock, Michael T.; Crowe Jr., James E.; Department of Pediatrics, IU School of Medicine
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    National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-Versus-Host Disease: III. The 2014 Biomarker Working Group Report
    (Elsevier B.V., 2015-05) Paczesny, Sophie; Hakim, Frances T.; Pidala, Joseph; Cooke, Kenneth; Lathrop, Julia; Griffith, Linda M.; Hansen, John; Jagasia, Madan; Miklos, David; Pavletic, Steven; Parkman, Robertson; Russek-Cohen, Estelle; Flowers, Mary E.D.; Lee, Stephanie; Martin, Paul; Vogelsang, Georgia; Walton, Marc; Schultz, Kirk R.; Department of Pediatrics, IU School of Medicine
    Biology-based markers to confirm or aid in the diagnosis or prognosis of chronic GVHD after allogeneic hematopoietic cell transplantation (HCT) or monitor its progression are critically needed to facilitate evaluation of new therapies. Biomarkers have been defined as any characteristic that is objectively measured and evaluated as an indicator of a normal biological or pathogenic process, a pharmacologic response to a therapeutic intervention. Applications of biomarkers in chronic GVHD clinical trials or patient management include: a) diagnosis and assessment of chronic GVHD disease activity, including distinguishing irreversible damage from continued disease activity, b) prognostic risk to develop chronic GVHD, and c) prediction of response to therapy. Sample collection for chronic GVHD biomarkers studies should be well-documented following established quality control guidelines for sample acquisition, processing, preservation and testing, at intervals that are both calendar- and event-driven. The consistent therapeutic treatment of subjects and standardized documentation needed to support biomarker studies are most likely to be provided in prospective clinical trials. To date, no chronic GVHD biomarkers have been qualified for utilization in clinical applications. Since our previous chronic GVHD Biomarkers Working Group report in 2005, an increasing number of chronic GVHD candidate biomarkers are available for further investigation. This paper provides a four-part framework for biomarker investigations: identification, verification, qualification, and application with terminology based on Food and Drug Administration and European Medicines Agency guidelines.
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    Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide
    (Elsevier, 2020-08) Im, Annie; Rashidi, Armin; Wang, Tao; Hemmer, Michael; MacMillan, Margaret L.; Pidala, Joseph; Jagasia, Madan; Pavletic, Steven; Majhail, Navneet S.; Weisdorf, Daniel; Abdel-Azim, Hisham; Agrawal, Vaibhav; Al-Homsi, A. Samer; Aljurf, Mahmoud; Askar, Medhat; Auletta, Jeffery J.; Bashey, Asad; Beitinjaneh, Amer; Bhatt, Vijaya Raj; Byrne, Michael; Cahn, Jean-Yves; Cairo, Mitchell; Castillo, Paul; Cerny, Jan; Chhabra, Saurabh; Choe, Hannah; Ciurea, Stefan; Daly, Andrew; Perez, Miguel Angel Diaz; Farhadfar, Nosha; Gadalla, Shahinaz M.; Gale, Robert; Ganguly, Siddhartha; Gergis, Usama; Hanna, Rabi; Hematti, Peiman; Herzig, Roger; Hildebrandt, Gerhard C.; Lad, Deepesh P.; Lee, Catherine; Lehmann, Leslie; Lekakis, Lazaros; Kamble, Rammurti T.; Kharfan-Dabaja, Mohamed A.; Khandelwal, Pooja; Martino, Rodrigo; Murthy, Hemant S.; Nishihori, Taiga; O'Brien, Tracey A.; Olsson, Richard F.; Patel, Sagar S.; Perales, Miguel-Angel; Prestidge, Tim; Qayed, Muna; Romee, Rizwan; Schoemans, Hélène; Seo, Sachiko; Sharma, Akshay; Solh, Melhem; Strair, Roger; Teshima, Takanori; Urbano-Ispizua, Alvaro; Van der Poel, Marjolein; Vij, Ravi; Wagner, John L.; William, Basem; Wirk, Baldeep; Yared, Jean A.; Spellman, Steve R.; Arora, Mukta; Hamilton, Betty K.; Medicine, School of Medicine
    Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P = .002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P < .001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P = .01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P = .01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival.