Stefanie Sarantopoulos

Positions:

Professor of Medicine

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Professor of Immunology

Immunology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1998

Boston University

Ph.D. 1998

Boston University School of Medicine

Intern, Internal Medicine

Boston University School of Medicine

Resident, Internal Medicine

Boston University School of Medicine

Chief Resident, Internal Medicine

Boston University School of Medicine

Fellowship, Hematology/ Oncology

Dana-Farber Cancer Institute

Grants:

BAFF Pathology: Novel Therapeutic Targets in Chronic Graft versus Host Disease

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Breaking B-Cell Tolerance to Produce Antibodies that Eradicate Leukemias and Lymphomas

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
Department of Defense
Role
Principal Investigator
Start Date
End Date

The Notch2-BCR Axis: Targeting Drivers of B cell Fate in Chronic GVHD

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
Leukemia & Lymphoma Society
Role
Principal Investigator
Start Date
End Date

Understanding Aberrant TLR7 Signaling in B Cells from Patients with Chronic GVHD

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
American Society for Blood and Marrow Transplantation
Role
Principal Investigator
Start Date
End Date

A Phase II of Entospletinib, a SYK Inhibitor, First line cGVHD patients

Administered By
Duke Cancer Institute
Awarded By
Gilead Sciences, Inc.
Role
Principal Investigator
Start Date
End Date

Publications:

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: III. The 2020 Treatment of Chronic GVHD Report.

Positive results from recent clinical trials have significantly expanded current therapeutic options for patients with chronic graft-versus-host disease (GVHD). However, new insights into the associations between clinical characteristics of chronic GVHD, pathophysiologic mechanisms of disease, and the clinical and biological effects of novel therapeutic agents are required to allow for a more individualized approach to treatment. The current report is focused on setting research priorities and direction in the treatment of chronic GVHD. Detailed correlative scientific studies should be conducted in the context of clinical trials to evaluate associations between clinical outcomes and the biological effect of systemic therapeutics. For patients who require systemic therapy but not urgent initiation of glucocorticoids, clinical trials for initial systemic treatment of chronic GVHD should investigate novel agents as monotherapy without concurrently starting glucocorticoids, to avoid confounding biological, pathological, and clinical assessments. Clinical trials for treatment-refractory disease should specifically target patients with incomplete or suboptimal responses to most recent therapy who are early in their disease course. Close collaboration between academic medical centers, medical societies, and industry is needed to support an individualized, biology-based strategic approach to chronic GVHD therapy.
Authors
DeFilipp, Z; Couriel, DR; Lazaryan, A; Bhatt, VR; Buxbaum, NP; Alousi, AM; Olivieri, A; Pulanic, D; Halter, JP; Henderson, LA; Zeiser, R; Gooley, TA; MacDonald, KPA; Wolff, D; Schultz, KR; Paczesny, S; Inamoto, Y; Cutler, CS; Kitko, CL; Pidala, JA; Lee, SJ; Socie, G; Sarantopoulos, S; Pavletic, SZ; Martin, PJ; Blazar, BR; Greinix, HT
MLA Citation
DeFilipp, Zachariah, et al. “National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: III. The 2020 Treatment of Chronic GVHD Report.Transplant Cell Ther, vol. 27, no. 9, Sept. 2021, pp. 729–37. Pubmed, doi:10.1016/j.jtct.2021.05.004.
URI
https://scholars.duke.edu/individual/pub1486126
PMID
34147469
Source
pubmed
Published In
Transplant Cell Ther
Volume
27
Published Date
Start Page
729
End Page
737
DOI
10.1016/j.jtct.2021.05.004

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IIb. The 2020 Preemptive Therapy Working Group Report.

Chronic graft-versus-host disease (GVHD) commonly occurs after allogeneic hematopoietic cell transplantation (HCT) despite standard prophylactic immune suppression. Intensified universal prophylaxis approaches are effective but risk possible overtreatment and may interfere with the graft-versus-malignancy immune response. Here we summarize conceptual and practical considerations regarding preemptive therapy of chronic GVHD, namely interventions applied after HCT based on evidence that the risk of developing chronic GVHD is higher than previously appreciated. This risk may be anticipated by clinical factors or risk assignment biomarkers or may be indicated by early signs and symptoms of chronic GVHD that do not fully meet National Institutes of Health diagnostic criteria. However, truly preemptive, individualized, and targeted chronic GVHD therapies currently do not exist. In this report, we (1) review current knowledge regarding clinical risk factors for chronic GVHD, (2) review what is known about chronic GVHD risk assignment biomarkers, (3) examine how chronic GVHD pathogenesis intersects with available targeted therapeutic agents, and (4) summarize considerations for preemptive therapy for chronic GVHD, emphasizing trial development, including trial design and statistical considerations. We conclude that robust risk assignment models that accurately predict chronic GVHD after HCT and early-phase preemptive therapy trials represent the most urgent priorities for advancing this novel area of research.
Authors
Pidala, J; Kitko, C; Lee, SJ; Carpenter, P; Cuvelier, GDE; Holtan, S; Flowers, ME; Cutler, C; Jagasia, M; Gooley, T; Palmer, J; Randolph, T; Levine, JE; Ayuk, F; Dignan, F; Schoemans, H; Tkaczyk, E; Farhadfar, N; Lawitschka, A; Schultz, KR; Martin, PJ; Sarantopoulos, S; Inamoto, Y; Socie, G; Wolff, D; Blazar, B; Greinix, H; Paczesny, S; Pavletic, S; Hill, G
MLA Citation
Pidala, Joseph, et al. “National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IIb. The 2020 Preemptive Therapy Working Group Report.Transplant Cell Ther, vol. 27, no. 8, Aug. 2021, pp. 632–41. Pubmed, doi:10.1016/j.jtct.2021.03.029.
URI
https://scholars.duke.edu/individual/pub1478582
PMID
33836313
Source
pubmed
Published In
Transplant Cell Ther
Volume
27
Published Date
Start Page
632
End Page
641
DOI
10.1016/j.jtct.2021.03.029

Decreased Mortality in 1-Year Survivors of Umbilical Cord Blood Transplant vs. Matched Related or Matched Unrelated Donor Transplant in Patients with Hematologic Malignancies.

Allogeneic hematopoietic stem cell transplantation (HCT) has the potential to cure hematologic malignancies but is associated with significant morbidity and mortality. Although deaths during the first year after transplantation are often attributable to treatment toxicities and complications, death after the first year may be due to sequelae of accelerated aging caused by cellular senescence. Cytotoxic therapies and radiation used in cancer treatments and conditioning regimens for HCT can induce aging at the molecular level; HCT patients experience time-dependent effects, such as frailty and aging-associated diseases, more rapidly than people who have not been exposed to these treatments. Consistent with this, recipients of younger cells tend to have decreased markers of aging and improved survival, decreased graft-versus-host disease, and lower relapse rates. Given that umbilical cord blood (UCB) is the youngest donor source available, we studied the outcomes after the first year of UCB transplantation versus matched related donor (MRD) and matched unrelated donor (MUD) transplantation in patients with hematologic malignancies over a 20-year period. In this single-center, retrospective study, we examined the outcomes of all adult patients who underwent their first allogeneic HCT through the Duke Adult Bone Marrow Transplant program from January 1, 1996, to December 31, 2015, to allow for at least 3 years of follow-up. Patients were excluded if they died or were lost to follow-up before day 365 after HCT, received an allogeneic HCT for a disease other than a hematologic malignancy, or received cells from a haploidentical or mismatched adult donor. UCB recipients experienced a better unadjusted overall survival than MRD/MUD recipients (log rank P = .03, median overall survival: UCB not reached, MRD/MUD 7.4 years). After adjusting for selected covariates, UCB recipients who survived at least 1 year after HCT had a hazard of death that was 31% lower than that of MRD/MUD recipients (hazard ratio, 0.69; 95% confidence interval, 0.47-0.99; P = .049). This trend held true in a subset analysis of subjects with acute leukemia. UCB recipients also experienced lower rates of moderate or severe chronic graft-versus-host disease (GVHD) and nonrelapse mortality, and slower time to relapse. UCB and MRD/MUD recipients experienced similar rates of grade 2-4 acute GVHD, chronic GHVD, secondary malignancy, and subsequent allogeneic HCT. UCB is already widely used as a donor source in pediatric HCT; however, adult outcomes and adoption have historically lagged behind in comparison. Recent advancements in UCB transplantation such as the implementation of lower-intensity conditioning regimens, double unit transplants, and ex vivo expansion have improved early mortality, making UCB an increasingly attractive donor source for adults; furthermore, our findings suggest that UCB may actually be a preferred donor source for mitigating late effects of HCT.
Authors
Bohannon, L; Tang, H; Page, K; Ren, Y; Jung, S-H; Artica, A; Britt, A; Islam, P; Siamakpour-Reihani, S; Giri, V; Lew, M; Kelly, M; Choi, T; Gasparetto, C; Long, G; Lopez, R; Rizzieri, D; Sarantopoulos, S; Chao, N; Horwitz, M; Sung, A
MLA Citation
Bohannon, Lauren, et al. “Decreased Mortality in 1-Year Survivors of Umbilical Cord Blood Transplant vs. Matched Related or Matched Unrelated Donor Transplant in Patients with Hematologic Malignancies.Transplant Cell Ther, vol. 27, no. 8, Aug. 2021, pp. 669.e1-669.e8. Pubmed, doi:10.1016/j.jtct.2021.05.002.
URI
https://scholars.duke.edu/individual/pub1482829
PMID
33991725
Source
pubmed
Published In
Transplant Cell Ther
Volume
27
Published Date
Start Page
669.e1
End Page
669.e8
DOI
10.1016/j.jtct.2021.05.002

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2020 Etiology and Prevention Working Group Report.

Preventing chronic graft-versus-host disease (GVHD) remains challenging because the unique cellular and molecular pathways that incite chronic GVHD are poorly understood. One major point of intervention for potential prevention of chronic GVHD occurs at the time of transplantation when acute donor anti-recipient immune responses first set the events in motion that result in chronic GVHD. After transplantation, additional insults causing tissue injury can incite aberrant immune responses and loss of tolerance, further contributing to chronic GVHD. Points of intervention are actively being identified so that chronic GVHD initiation pathways can be targeted without affecting immune function. The major objective in the field is to continue basic studies and to translate what is learned about etiopathology to develop targeted prevention strategies that decrease the risk of morbid chronic GVHD without increasing the risks of cancer relapse or infection. Development of strategies to predict the risk of developing debilitating or deadly chronic GVHD is a high research priority. This working group recommends further interrogation into the mechanisms underpinning chronic GVHD development, and we highlight considerations for future trial design in prevention trials.
Authors
Williams, KM; Inamoto, Y; Im, A; Hamilton, B; Koreth, J; Arora, M; Pusic, I; Mays, JW; Carpenter, PA; Luznik, L; Reddy, P; Ritz, J; Greinix, H; Paczesny, S; Blazar, BR; Pidala, J; Cutler, C; Wolff, D; Schultz, KR; Pavletic, SZ; Lee, SJ; Martin, PJ; Socie, G; Sarantopoulos, S
MLA Citation
Williams, Kirsten M., et al. “National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2020 Etiology and Prevention Working Group Report.Transplant Cell Ther, vol. 27, no. 6, June 2021, pp. 452–66. Pubmed, doi:10.1016/j.jtct.2021.02.035.
URI
https://scholars.duke.edu/individual/pub1480867
PMID
33877965
Source
pubmed
Published In
Transplant Cell Ther
Volume
27
Published Date
Start Page
452
End Page
466
DOI
10.1016/j.jtct.2021.02.035

Morphologic leukemia-free state in acute myeloid leukemia is sufficient for successful allogeneic hematopoietic stem cell transplant.

Authors
Pabon, CM; Li, Z; Hennig, T; de Castro, C; Neff, JL; Horwitz, ME; LeBlanc, TW; Long, GD; Lopez, RD; Sung, AD; Chao, N; Gasparetto, C; Sarantopoulos, S; Adams, DB; Erba, H; Rizzieri, DA
MLA Citation
Pabon, Cindy M., et al. “Morphologic leukemia-free state in acute myeloid leukemia is sufficient for successful allogeneic hematopoietic stem cell transplant.Blood Cancer J, vol. 11, no. 5, May 2021, p. 92. Pubmed, doi:10.1038/s41408-021-00481-9.
URI
https://scholars.duke.edu/individual/pub1482850
PMID
33994546
Source
pubmed
Published In
Blood Cancer Journal
Volume
11
Published Date
Start Page
92
DOI
10.1038/s41408-021-00481-9