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3. Obesity induces gut microbiota alterations and augments acute graft-versus-host disease after allogeneic stem cell transplantation

Author

Khuat, Lam T, Le, Catherine T, Pai, Chien-Chun Steven, Shields-Cutler, Robin R, Holtan, Shernan G, Rashidi, Armin, Parker, Sarah L, Knights, Dan, Luna, Jesus I, Dunai, Cordelia, Wang, Ziming, Sturgill, Ian R, Stoffel, Kevin M, Merleev, Alexander A, More, Shyam K, Maverakis, Emanual, Raybould, Helen E, Chen, Mingyi, Canter, Robert J, Monjazeb, Arta M, Dave, Maneesh, Ferrara, James LM, Levine, John E, Longo, Dan L, Abedi, Mehrdad, Blazar, Bruce R, and Murphy, William J

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Immunology, Prevention, Regenerative Medicine, Nutrition, Transplantation, Hematology, Obesity, Stem Cell Research - Nonembryonic - Non-Human, Rare Diseases, Stem Cell Research, Aetiology, 2.1 Biological and endogenous factors, Oral and gastrointestinal, Cancer, Acute Disease, Animals, Female, Gastrointestinal Microbiome, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Male, Mice, Retrospective Studies, Biological Sciences, Medical and Health Sciences, Medical biotechnology, Biomedical engineering
Abstract

The efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is limited by acute and chronic graft-versus-host disease (GVHD). The impact of obesity on allo-HSCT outcomes is poorly understood. Here, we report that obesity had a negative and selective impact on acute gut GVHD after allo-HSCT in mice with diet-induced obesity (DIO). These animals exhibited increased gut permeability, endotoxin translocation across the gut, and radiation-induced gastrointestinal damage after allo-HSCT. After allo-HSCT, both male and female DIO mouse recipients showed increased proinflammatory cytokine production and expression of the GVHD marker ST2 (IL-33R) and MHC class II molecules; they also exhibited decreased survival associated with acute severe gut GVHD. This rapid-onset, obesity-associated gut GVHD depended on donor CD4+ T cells and occurred even with a minor MHC mismatch between donor and recipient animals. Retrospective analysis of clinical cohorts receiving allo-HSCT transplants from unrelated donors revealed that recipients with a high body mass index (BMI, >30) had reduced survival and higher serum ST2 concentrations compared with nonobese transplant recipients. Assessment of both DIO mice and allo-HSCT recipients with a high BMI revealed reduced gut microbiota diversity and decreased Clostridiaceae abundance. Prophylactic antibiotic treatment protected DIO mouse recipients from endotoxin translocation across the gut and increased inflammatory cytokine production, as well as gut pathology and mortality, but did not protect against later development of chronic skin GVHD. These results suggest that obesity-induced alterations of the gut microbiota may affect GVHD after allo-HSCT in DIO mice, which could be ameliorated by prophylactic antibiotic treatment.

Published
2020

4. Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide.

Author

Im, Annie, Rashidi, Armin, Wang, Tao, Hemmer, Michael, MacMillan, Margaret, Pidala, Joseph, Jagasia, Madan, Pavletic, Steven, Majhail, Navneet, Weisdorf, Daniel, Abdel-Azim, Hisham, Agrawal, Vaibhav, Al-Homsi, A, Aljurf, Mahmoud, Askar, Medhat, Auletta, Jeffery, Bashey, Asad, Beitinjaneh, Amer, Bhatt, Vijaya, Byrne, Michael, Cahn, Jean-Yves, Cairo, Mitchell, Castillo, Paul, Cerny, Jan, Chhabra, Saurabh, Choe, Hannah, Ciurea, Stefan, Daly, Andrew, Perez, Miguel, Farhadfar, Nosha, Gadalla, Shahinaz, Gale, Robert, Ganguly, Siddhartha, Gergis, Usama, Hanna, Rabi, Hematti, Peiman, Herzig, Roger, Hildebrandt, Gerhard, Lad, Deepesh, Lee, Catherine, Lehmann, Leslie, Lekakis, Lazaros, Kamble, Rammurti, Kharfan-Dabaja, Mohamed, Khandelwal, Pooja, Martino, Rodrigo, Murthy, Hemant, Nishihori, Taiga, OBrien, Tracey, Olsson, Richard, Patel, Sagar, 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, William, Basem, Wirk, Baldeep, Yared, Jean, Spellman, Steve, Arora, Mukta, and Hamilton, Betty

Subjects
Adult, Cyclophosphamide, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Humans, Risk Factors, Transplantation Conditioning
Abstract

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

Published
2020

7. FIGURE 2 from Multi-omics Analysis of a Fecal Microbiota Transplantation Trial Identifies Novel Aspects of Acute GVHD Pathogenesis

Author

Rashidi, Armin, primary, Ebadi, Maryam, primary, Rehman, Tauseef U., primary, Elhusseini, Heba, primary, Kazadi, David, primary, Halaweish, Hossam, primary, Khan, Mohammad H., primary, Hoeschen, Andrea, primary, Cao, Qing, primary, Luo, Xianghua, primary, Kabage, Amanda J., primary, Lopez, Sharon, primary, Ramamoorthy, Sivapriya, primary, Holtan, Shernan G., primary, Weisdorf, Daniel J., primary, Khoruts, Alexander, primary, and Staley, Christopher, primary

Published
2024
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8. FIGURE 3 from Multi-omics Analysis of a Fecal Microbiota Transplantation Trial Identifies Novel Aspects of Acute GVHD Pathogenesis

Author

Rashidi, Armin, primary, Ebadi, Maryam, primary, Rehman, Tauseef U., primary, Elhusseini, Heba, primary, Kazadi, David, primary, Halaweish, Hossam, primary, Khan, Mohammad H., primary, Hoeschen, Andrea, primary, Cao, Qing, primary, Luo, Xianghua, primary, Kabage, Amanda J., primary, Lopez, Sharon, primary, Ramamoorthy, Sivapriya, primary, Holtan, Shernan G., primary, Weisdorf, Daniel J., primary, Khoruts, Alexander, primary, and Staley, Christopher, primary

Published
2024
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9. FIGURE 4 from Multi-omics Analysis of a Fecal Microbiota Transplantation Trial Identifies Novel Aspects of Acute GVHD Pathogenesis

Author

Rashidi, Armin, primary, Ebadi, Maryam, primary, Rehman, Tauseef U., primary, Elhusseini, Heba, primary, Kazadi, David, primary, Halaweish, Hossam, primary, Khan, Mohammad H., primary, Hoeschen, Andrea, primary, Cao, Qing, primary, Luo, Xianghua, primary, Kabage, Amanda J., primary, Lopez, Sharon, primary, Ramamoorthy, Sivapriya, primary, Holtan, Shernan G., primary, Weisdorf, Daniel J., primary, Khoruts, Alexander, primary, and Staley, Christopher, primary

Published
2024
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10. Table S1 from Multi-omics Analysis of a Fecal Microbiota Transplantation Trial Identifies Novel Aspects of Acute GVHD Pathogenesis

Author

Rashidi, Armin, primary, Ebadi, Maryam, primary, Rehman, Tauseef U., primary, Elhusseini, Heba, primary, Kazadi, David, primary, Halaweish, Hossam, primary, Khan, Mohammad H., primary, Hoeschen, Andrea, primary, Cao, Qing, primary, Luo, Xianghua, primary, Kabage, Amanda J., primary, Lopez, Sharon, primary, Ramamoorthy, Sivapriya, primary, Holtan, Shernan G., primary, Weisdorf, Daniel J., primary, Khoruts, Alexander, primary, and Staley, Christopher, primary

Published
2024
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11. FIGURE 5 from Multi-omics Analysis of a Fecal Microbiota Transplantation Trial Identifies Novel Aspects of Acute GVHD Pathogenesis

Author

Rashidi, Armin, primary, Ebadi, Maryam, primary, Rehman, Tauseef U., primary, Elhusseini, Heba, primary, Kazadi, David, primary, Halaweish, Hossam, primary, Khan, Mohammad H., primary, Hoeschen, Andrea, primary, Cao, Qing, primary, Luo, Xianghua, primary, Kabage, Amanda J., primary, Lopez, Sharon, primary, Ramamoorthy, Sivapriya, primary, Holtan, Shernan G., primary, Weisdorf, Daniel J., primary, Khoruts, Alexander, primary, and Staley, Christopher, primary

Published
2024
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12. Data from Multi-omics Analysis of a Fecal Microbiota Transplantation Trial Identifies Novel Aspects of Acute GVHD Pathogenesis

Author

Rashidi, Armin, primary, Ebadi, Maryam, primary, Rehman, Tauseef U., primary, Elhusseini, Heba, primary, Kazadi, David, primary, Halaweish, Hossam, primary, Khan, Mohammad H., primary, Hoeschen, Andrea, primary, Cao, Qing, primary, Luo, Xianghua, primary, Kabage, Amanda J., primary, Lopez, Sharon, primary, Ramamoorthy, Sivapriya, primary, Holtan, Shernan G., primary, Weisdorf, Daniel J., primary, Khoruts, Alexander, primary, and Staley, Christopher, primary

Published
2024
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13. TABLE 1 from Multi-omics Analysis of a Fecal Microbiota Transplantation Trial Identifies Novel Aspects of Acute GVHD Pathogenesis

Author

Rashidi, Armin, primary, Ebadi, Maryam, primary, Rehman, Tauseef U., primary, Elhusseini, Heba, primary, Kazadi, David, primary, Halaweish, Hossam, primary, Khan, Mohammad H., primary, Hoeschen, Andrea, primary, Cao, Qing, primary, Luo, Xianghua, primary, Kabage, Amanda J., primary, Lopez, Sharon, primary, Ramamoorthy, Sivapriya, primary, Holtan, Shernan G., primary, Weisdorf, Daniel J., primary, Khoruts, Alexander, primary, and Staley, Christopher, primary

Published
2024
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16. Outcomes of haploidentical vs matched sibling transplantation for acute myeloid leukemia in first complete remission.

Author

Rashidi, Armin, Hamadani, Mehdi, Zhang, Mei-Jie, Wang, Hai-Lin, Abdel-Azim, Hisham, Aljurf, Mahmoud, Assal, Amer, Bajel, Ashish, Bashey, Asad, Battiwalla, Minoo, Beitinjaneh, Amer, Bejanyan, Nelli, Bhatt, Vijaya, Bolaños-Meade, Javier, Byrne, Michael, Cahn, Jean-Yves, Cairo, Mitchell, Ciurea, Stefan, Copelan, Edward, Cutler, Corey, Daly, Andrew, Diaz, Miguel-Angel, Farhadfar, Nosha, Gale, Robert, Ganguly, Siddhartha, Grunwald, Michael, Hahn, Theresa, Hashmi, Shahrukh, Hildebrandt, Gerhard, Holland, H, Hossain, Nasheed, Kanakry, Christopher, Kharfan-Dabaja, Mohamed, Khera, Nandita, Koc, Yener, Lazarus, Hillard, Lee, Jong-Wook, Maertens, Johan, Martino, Rodrigo, McGuirk, Joseph, Munker, Reinhold, Murthy, Hemant, Nakamura, Ryotaro, Nathan, Sunita, Nishihori, Taiga, Palmisiano, Neil, Patel, Sagar, Pidala, Joseph, Olin, Rebecca, Olsson, Richard, Oran, Betul, Ringden, Olov, Rizzieri, David, Rowe, Jacob, Savoie, Mary, Schultz, Kirk, Seo, Sachiko, Shaffer, Brian, Singh, Anurag, Solh, Melhem, Stockerl-Goldstein, Keith, Verdonck, Leo, Wagner, John, Waller, Edmund, De Lima, Marcos, Sandmaier, Brenda, Litzow, Mark, Weisdorf, Dan, Romee, Rizwan, and Saber, Wael

Subjects
Adolescent, Adult, Aged, Blood Donors, Bone Marrow Transplantation, Calcineurin Inhibitors, Chronic Disease, Cyclophosphamide, Disease-Free Survival, Female, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Humans, Immunosuppressive Agents, Incidence, Leukemia, Myeloid, Acute, Male, Middle Aged, Recurrence, Remission Induction, Retrospective Studies, Siblings, Survival Analysis, Transplantation Conditioning, Transplantation, Haploidentical, Young Adult
Abstract

HLA-haploidentical hematopoietic cell transplantation (Haplo-HCT) using posttransplantation cyclophosphamide (PT-Cy) has improved donor availability. However, a matched sibling donor (MSD) is still considered the optimal donor. Using the Center for International Blood and Marrow Transplant Research database, we compared outcomes after Haplo-HCT vs MSD in patients with acute myeloid leukemia (AML) in first complete remission (CR1). Data from 1205 adult CR1 AML patients (2008-2015) were analyzed. A total of 336 patients underwent PT-Cy-based Haplo-HCT and 869 underwent MSD using calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis. The Haplo-HCT group included more reduced-intensity conditioning (65% vs 30%) and bone marrow grafts (62% vs 7%), consistent with current practice. In multivariable analysis, Haplo-HCT and MSD groups were not different with regard to overall survival (P = .15), leukemia-free survival (P = .50), nonrelapse mortality (P = .16), relapse (P = .90), or grade II-IV acute GVHD (P = .98). However, the Haplo-HCT group had a significantly lower rate of chronic GVHD (hazard ratio, 0.38; 95% confidence interval, 0.30-0.48; P < .001). Results of subgroup analyses by conditioning intensity and graft source suggested that the reduced incidence of chronic GVHD in Haplo-HCT is not limited to a specific graft source or conditioning intensity. Center effect and minimal residual disease-donor type interaction were not predictors of outcome. Our results indicate a lower rate of chronic GVHD after PT-Cy-based Haplo-HCT vs MSD using calcineurin inhibitor-based GVHD prophylaxis, but similar other outcomes, in patients with AML in CR1. Haplo-HCT is a viable alternative to MSD in these patients.

Published
2019

19. Long- and short-term effects of fecal microbiota transplantation on antibiotic resistance genes: results from a randomized placebo-controlled trial

Author

Rashidi, Armin, primary, Ebadi, Maryam, additional, Rehman, Tauseef Ur, additional, Elhusseini, Heba, additional, Kazadi, David, additional, Halaweish, Hossam, additional, Khan, Mohammad H., additional, Hoeschen, Andrea, additional, Cao, Qing, additional, Luo, Xianghua, additional, Kabage, Amanda J., additional, Lopez, Sharon, additional, Holtan, Shernan G., additional, Weisdorf, Daniel J., additional, Liu, Chang, additional, Ishii, Satoshi, additional, Khoruts, Alexander, additional, and Staley, Christopher, additional

Published
2024
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20. A phase II randomized, placebo-controlled, multicenter trial to evaluate the efficacy of cytomegalovirus PepVax vaccine in preventing cytomegalovirus reactivation and disease after allogeneic hematopoietic stem cell transplant

Author

Nakamura, Ryotaro, primary, La Rosa, Corinna, additional, Yang, Dongyun, additional, Hill, Joshua A., additional, Rashidi, Armin, additional, Choe, Hannah, additional, Zhou, Qiao, additional, Lingaraju, Chetan Raj, additional, Kaltcheva, Teodora, additional, Longmate, Jeffrey, additional, Drake, Jennifer, additional, Slape, Cynthia, additional, Duarte, Lupe, additional, Al Malki, Monzr M., additional, Pullarkat, Vinod A., additional, Aribi, Ahmed, additional, Devine, Steven, additional, Verneris, Michael R., additional, Miller, Jeffrey S., additional, Forman, Stephen J., additional, Aldoss, Ibrahim, additional, and Diamond, Don J., additional

Published
2024
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24. Phase II Study of Myeloablative 7-8/8-Matched Allotransplantation with Post-Transplantation Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil

Author

Jurdi, Najla El, Hoover, Alex, O'Leary, Daniel, Cao, Qing, Gupta, Ashish, Ebens, Christen, Maakaron, Joseph E., Betts, Brian C., Rashidi, Armin, Juckett, Mark B., Lund, Troy, Bachanova, Veronika, MacMillan, Margaret L, Miller, Jeffrey S., Orchard, Paul J., Wagner, John E., Vercellotti, Gregory, Weisdorf, Daniel J., Dusenbery, Kathryn, Terezakis, Stephanie, and Holtan, Shernan G.

Published
2023
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25. Phase II, Open-Label Clinical Trial of Urinary-Derived Human Chorionic Gonadotropin/Epidermal Growth Factor for Life-Threatening Acute Graft-versus-Host Disease

Author

Holtan, Shernan G., Hoeschen, Andrea, Cao, Qing, Ustun, Celalettin, Betts, Brian C., Jurdi, Najla El, Maakaron, Joseph, Rashidi, Armin, Miller, Jeffrey S., Wagner, John E., Blazar, Bruce R., Jacobson, Pamala A., Panoskaltsis-Mortari, Angela, Weisdorf, Daniel J., and MacMillan, Margaret L.

Published
2023
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29. Levaquin Gets a Pass

Author

Rashidi, Armin, Kaiser, Thomas, Holtan, Shernan G., Rehman, Tauseef Ur, Weisdorf, Daniel J., Khoruts, Alexander, and Staley, Christopher

Published
2020
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31. Randomized Double-Blind Phase II Trial of Fecal Microbiota Transplantation Versus Placebo in Allogeneic Hematopoietic Cell Transplantation and AML

Author

Rashidi, Armin, primary, Ebadi, Maryam, additional, Rehman, Tauseef Ur, additional, Elhusseini, Heba, additional, Kazadi, David, additional, Halaweish, Hossam, additional, Khan, Mohammad H., additional, Hoeschen, Andrea, additional, Cao, Qing, additional, Luo, Xianghua, additional, Kabage, Amanda J., additional, Lopez, Sharon, additional, Holtan, Shernan G., additional, Weisdorf, Daniel J., additional, Khoruts, Alexander, additional, and Staley, Christopher, additional

Published
2023
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41. High incidence of thromboembolism in patients with chronic GVHD: association with severity of GVHD and donor-recipient ABO blood group

Author

El Jurdi, Najla, Elhusseini, Heba, Beckman, Joan, DeFor, Todd E., Okoev, Grigori, Rogosheske, John, Lazaryan, Aleksandr, Weiler, Kristen, Bachanova, Veronika, Betts, Brian C., Blazar, Bruce R., Brunstein, Claudio G., He, Fiona, Holtan, Shernan G., Janakiram, Murali, Gangaraju, Radhika, Maakaron, Joseph, MacMillan, Margaret L., Rashidi, Armin, Warlick, Erica D., Bhatia, Smita, Vercellotti, Gregory, Weisdorf, Daniel J., and Arora, Mukta

Published
2021
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42. Potential of Fecal Microbiota Transplantation to Prevent Acute GVHD: Analysis from a Phase II Trial

Author

Rashidi, Armin, primary, Ebadi, Maryam, additional, Rehman, Tauseef Ur, additional, Elhusseini, Heba, additional, Kazadi, David, additional, Halaweish, Hossam, additional, Khan, Mohammad H., additional, Hoeschen, Andrea, additional, Cao, Qing, additional, Luo, Xianghua, additional, Kabage, Amanda J., additional, Lopez, Sharon, additional, Holtan, Shernan G., additional, Weisdorf, Daniel J., additional, Khoruts, Alexander, additional, and Staley, Christopher, additional

Published
2023
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43. Amphiregulin as monitoring biomarker for life-threatening acute graft-versushost disease: secondary analysis of two prospective clinical trials

Author

Holtan, Shernan G., primary, El Jurdi, Najla, additional, Rashidi, Armin, additional, Betts, Brian C., additional, Demorest, Connor, additional, Galvin, John P, additional, MacMillan, Margaret L., additional, Weisdorf, Daniel J., additional, Panoskaltsis-Mortari, Angela, additional, and Pratta, Michael A., additional

Published
2023
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44. Pre‐transplant and longitudinal changes in faecal microbiome characteristics are associated with subsequent development of chronic graft‐versus‐host disease

Author

El Jurdi, Najla, primary, Holtan, Shernan G., additional, Hoeschen, Andrea, additional, Velguth, Jessica, additional, Hillmann, Benjamin, additional, Betts, Brian C., additional, MacMillan, Margaret L., additional, Weisdorf, Daniel J., additional, Khoruts, Alexander, additional, Rashidi, Armin, additional, and Shields‐Cutler, Robin, additional

Published
2023
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49. A systems-level approach to the evolution of ageing

Author

Rashidi, Armin

Subjects
616.07
Abstract

Ageing as a biological process is ubiquitous in life. In humans, ageing and its related conditions are revealed with improvements in health care conditions. Evidence for ageing is also apparent in most other organisms including unicellular species. Many of the pathways and mechanisms involved in ageing are evolutionarily conserved across the tree of life which provides an exceptional opportunity to study simpler organisms and extend the results to more complex forms of life. There is a rapidly growing body of data from organisms of varying levels of complexity, but there is a shortage of attempts in coherently making use of these data. A systems-level approach is necessary to bridge the gap between different biological levels, integrate the available information, and enable the synthesis of unifying hypotheses. Also, given the evolutionary nature of the question at hand (i.e. ageing), a successful hypothesis needs to be able to account for evolutionary considerations. In this thesis, I take a theoretical approach and try to explain a number of aspects of ageing from a systems-level perspective in an evolutionary context. Among the topics that will be covered are the following: (i) intra-islet pancreatic beta-cell dynamics, (ii) antioxidant defence system in pancreatic beta-cells, (iii) metabolic evolution of the glucose homeostatic system, and (iv) asymmetric damage segregation in unicellular organisms. In (i), I investigate the dynamics of beta-cell number within pancreatic islets and link the results to pathophysiology of diabetes and its various stages. In (ii) and (iii), I provide a unifying hypothesis for the paradoxical and unequivocal observation that metabolically active beta-cells have a weak antioxidant defence system and interestingly, that they are particularly weak in females. In (iv), I show how asymmetric segregation of damage at the time of mitosis is a fundamental step toward ageing and then evaluate whether and by how much asymmetry is optimal in a given organism under certain environmental conditions. I use a variety of techniques including deterministic and stochastic modelling in this thesis. The shared essence of these projects is an attempt to put data of various sources together in a unifying, systems-level evolutionary framework in order to better understand some aspects of the ageing process and its consequences.

Published
2011

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