Nelson Chao

Overview:

My research interests are in two broad areas, clinical hematopoietic stem cell and cord blood transplantation and in the laboratory studies related to graft vs. host disease and immune reconstitution. On the clinical side we are currently conducting approximately 50 different clinical protocols ranging from preparatory regimens, supportive care studies and disease specific protocols. Most of these clinical studies are centered around studies of the sources of stem cells and the methods to improve the long term outcome. There are exploratory protocols for novel therapies such as dendritic cell therapy for several malignancies, antiangiogenesis therapy, graft engineering to prevent graft-versus-host disease and antigen specific T cells or non specific NK cells to prevent relapse. Moreover a strong focus of the program is to develop cord-blood transplantation for adult patients with hematologic malignancies. The laboratory studies center on understanding the immunological events that occur with graft-vs-host disease and methods to prevent this disease. The current efforts focus on understanding murine reconstitution following transplantation, use of a peptide polymer to block MHC class II recognition of minor histocompatibility antigens, use of T cell engineering to prevent graft-versus-host disease at the same time preserving a graft-versus-malignancy effect.

For more information see http://ed-media.mc.duke.edu/BMT.nsf

Positions:

Donald D. and Elizabeth G. Cooke Cancer Distinguished Research Professor

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Professor of Medicine

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Professor in Immunology

Immunology
School of Medicine

Research Professor of Global Health

Duke Global Health Institute
Institutes and Provost's Academic Units

Professor in Pathology

Pathology
School of Medicine

Chief, Division of Cell Therapy in the Department of Medicine

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Affiliate of the Duke Regeneration Center

Regeneration Next Initiative
School of Medicine

Education:

M.D. 1981

Yale University

Medical Resident, Medicine

Stanford University

Fellow in Oncology, Medicine

Stanford University

Grants:

Clinical Presentation, Treatment, and Outcomes of Grade 2-4 Acute Graft Versus Host Disease (GVHD) Patients after Allogeneic Hematopoietic Stem Call Transplants (HSCT): A Multi-Center Chart Audit Study

Administered By
Duke Cancer Institute
Awarded By
Incyte Corporation
Role
Principal Investigator
Start Date
End Date

Centers for Medical Countermeasures against Radiation Consortium

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

Clinical Validation and Supply of SRI Radiation Biodosimeter

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
SRI International
Role
Principal Investigator
Start Date
End Date

RITN Opportunity for Radiological Preparedness

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
National Marrow Donor Program
Role
Principal Investigator
Start Date
End Date

Determining the mechanism of the protective of action of STO-609, a CaMKK2 inhibitor, in acute radiation syndrome

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
Columbia University
Role
Collaborator
Start Date
End Date

Publications:

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

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

Finally, a Successful Randomized Trial for GVHD.

Authors
MLA Citation
Chao, Nelson. “Finally, a Successful Randomized Trial for GVHD.N Engl J Med, vol. 382, no. 19, May 2020, pp. 1853–54. Pubmed, doi:10.1056/NEJMe2003331.
URI
https://scholars.duke.edu/individual/pub1486375
PMID
32320558
Source
pubmed
Published In
The New England Journal of Medicine
Volume
382
Published Date
Start Page
1853
End Page
1854
DOI
10.1056/NEJMe2003331

A phase 2 trial of the somatostatin analog pasireotide to prevent GI toxicity and acute GVHD in allogeneic hematopoietic stem cell transplant.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HCT) is an often curative intent treatment, however it is associated with significant gastrointestinal (GI) toxicity and treatment related mortality. Graft-versus-host disease is a significant contributor to transplant-related mortality. We performed a phase 2 trial of the somatostatin analog pasireotide to prevent gastrointestinal toxicity and GVHD after myeloablative allogeneic HCT. METHODS: Patients received 0.9mg pasireotide every 12 hours from the day prior to conditioning through day +4 after HCT (or a maximum of 14 days). The primary outcomes were grade 3-4 gastrointestinal toxicity through day 30 and acute GVHD. Secondary outcomes were chronic GVHD, overall survival and relapse free survival at one year. Stool and blood samples were collected from before and after HCT for analyses of stool microbiome, local inflammatory markers, and systemic inflammatory and metabolic markers. Results were compared with matched controls. RESULTS: Twenty-six patients received pasireotide and were compared to 52 matched contemporaneous controls using a 1-2 match. Grade 3-4 GI toxicity occurred in 21 (81%) patients who received pasireotide and 35 (67%) controls (p = 0.33). Acute GVHD occurred in 15 (58%) patients in the pasireotide group and 28 (54%) controls (p = 0.94). Chronic GVHD occurred in 16 patients in the pasireotide group (64%) versus 22 patients in the control group (42%) (p = 0.12). Overall survival at 1 year in the pasireotide group was 63% (95% CI: 47%,86%) versus 82% (95% CI: 72%, 93%) in controls (log-rank p = 0.006). Relapse-free survival rate at one year was 40% (95% CI: 25%, 65%) in the pasireotide group versus 78% (95% CI: 68%, 91%) in controls (log-rank p = 0.002). After controlling for the effect of relevant covariates, patients in the pasireotide group had attenuated post-HCT loss of microbial diversity. Analysis of systemic inflammatory markers and metabolomics demonstrated feasibility of such analyses in patients undergoing allogeneic HCT. Baseline level and pre-to-post transplant changes in several inflammatory markers (including MIP1a, MIP1b, TNFa, IL8Pro, and IL6) correlated with likelihood of survival. CONCLUSIONS: Pasireotide did not prevent gastrointestinal toxicity or acute GVHD compared to contemporaneous controls. Pasireotide was associated with numerically higher chronic GVHD and significantly decreased OS and RFS compared to contemporaneous controls. Pasireotide may provide a locally protective effect in the stool microbiome and in local inflammation as measured by stool calprotectin, stool beta-defensin, and stool diversity index.
Authors
Ramalingam, S; Siamakpour-Reihani, S; Bohannan, L; Ren, Y; Sibley, A; Sheng, J; Ma, L; Nixon, AB; Lyu, J; Parker, DC; Bain, J; Muehlbauer, M; Ilkayeva, O; Kraus, VB; Huebner, JL; Spitzer, T; Brown, J; Peled, JU; van den Brink, M; Gomes, A; Choi, T; Gasparetto, C; Horwitz, M; Long, G; Lopez, R; Rizzieri, D; Sarantopoulos, S; Chao, N; Sung, AD
MLA Citation
Ramalingam, Sendhilnathan, et al. “A phase 2 trial of the somatostatin analog pasireotide to prevent GI toxicity and acute GVHD in allogeneic hematopoietic stem cell transplant.Plos One, vol. 16, no. 6, 2021, p. e0252995. Pubmed, doi:10.1371/journal.pone.0252995.
URI
https://scholars.duke.edu/individual/pub1487527
PMID
34170918
Source
pubmed
Published In
Plos One
Volume
16
Published Date
Start Page
e0252995
DOI
10.1371/journal.pone.0252995

Correction to: Impact of depth of clinical response on outcomes of acute myeloid leukemia patients in first complete remission who undergo allogeneic hematopoietic cell transplantation.

Authors
Percival, M-E; Wang, H-L; Zhang, M-J; Saber, W; de Lima, M; Litzow, M; Kebriaei, P; Abdel-Azim, H; Adekola, K; Aljurf, M; Bacher, U; Badawy, SM; Beitinjaneh, A; Bejanyan, N; Bhatt, V; Byrne, M; Cahn, J-Y; Castillo, P; Chao, N; Chhabra, S; Copelan, E; Cutler, C; DeFilipp, Z; Dias, A; Diaz, MA; Estey, E; Farhadfar, N; Frangoul, HA; Freytes, CO; Gale, RP; Ganguly, S; Gowda, L; Grunwald, M; Hossain, N; Kamble, RT; Kanakry, CG; Kansagra, A; Kharfan-Dabaja, MA; Krem, M; Lazarus, HM; Lee, JW; Liesveld, JL; Lin, R; Liu, H; McGuirk, J; Munker, R; Murthy, HS; Nathan, S; Nishihori, T; Olsson, RF; Palmisiano, N; Passweg, JR; Prestidge, T; Ringdén, O; Rizzieri, DA; Rybka, WB; Savoie, ML; Schultz, KR; Seo, S; Sharma, A; Solh, M; Strair, R; van der Poel, M; Verdonck, LF; Yared, JA; Weisdorf, D; Sandmaier, BM
MLA Citation
Percival, Mary-Elizabeth, et al. “Correction to: Impact of depth of clinical response on outcomes of acute myeloid leukemia patients in first complete remission who undergo allogeneic hematopoietic cell transplantation.Bone Marrow Transplant, vol. 56, no. 9, Sept. 2021, p. 2319. Pubmed, doi:10.1038/s41409-021-01353-3.
URI
https://scholars.duke.edu/individual/pub1483330
PMID
34017072
Source
pubmed
Published In
Bone Marrow Transplant
Volume
56
Published Date
Start Page
2319
DOI
10.1038/s41409-021-01353-3