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:

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

Female Sex Is Associated with Improved Long-Term Survival Following Allogeneic Hematopoietic Stem Cell Transplantation.

Life expectancy for long-term survivors of allogeneic hematopoietic stem cell transplantation (alloHSCT), defined as those living ≥5 years post-transplantation, is significantly lower compared with that of the age-matched general population despite a relatively low primary disease relapse rate at >2 years post-transplantation. Among several factors, patient sex is increasingly recognized as a prognostic indicator of long-term survival. We examined the influence of patient sex and donor-recipient sex matching on overall survival (OS) in a landmark analysis of long-term survivors. Using our institutional database supplemented with individual patient record review, we retrospectively investigated the relative influence of recipient sex and donor-recipient sex matching on outcomes of long-term survivors of alloHSCT between 1994 and 2014. Over this 20-year period, 247 met inclusion criteria for analysis; males and females had similar demographic and treatment characteristics. However, significantly more deaths after the 5-year landmark occurred in male recipients. Interestingly, donor sex did not have a significant impact on OS in multivariate analysis, and differences in OS of donor-recipient sex pairs was driven by recipient sex. In addition to recipient sex, only chronic graft-versus-host disease (cGVHD) retained significance as a covariate with an impact on OS in multivariate analysis. Men experienced slightly higher, but statistically nonsignificant, rates and increased severity of cGVHD, and had higher cGVHD-related mortality compared with females. In this long-term survival analysis of adult alloHSCT recipients, one of the only to include follow-up to 15 years, our results show that women survive significantly longer than men irrespective of their age at transplantation. This outcome is independent of other common pretransplantation prognostic indicators, such as donor sex or performance status at transplantation. The inferior survival in males is consistent with survival outcomes described in the transplantation literature. Increasing evidence suggests a biological basis for long-term sex-determined outcomes, possibly owing to differing rates or severity of cGVHD or sustained alloimmune tolerance in females. Larger studies are warranted to validate these retrospective clinical results.
Authors
Islam, P; Tang, H; Jin, H; Cao, F; Bohannon, LM; Ren, Y; Chao, NJ; Choi, T; Gasparetto, C; Horwitz, ME; Long, GD; Lopez, RD; Rizzieri, DA; Sarantopoulos, S; Sung, AD
MLA Citation
Islam, Prioty, et al. “Female Sex Is Associated with Improved Long-Term Survival Following Allogeneic Hematopoietic Stem Cell Transplantation.Transplant Cell Ther, vol. 27, no. 9, Sept. 2021, pp. 784.e1-784.e7. Pubmed, doi:10.1016/j.jtct.2021.06.012.
URI
https://scholars.duke.edu/individual/pub1485675
PMID
34146734
Source
pubmed
Published In
Transplant Cell Ther
Volume
27
Published Date
Start Page
784.e1
End Page
784.e7
DOI
10.1016/j.jtct.2021.06.012

Homecare Encounters: An Organizational Response to Innovative Care for Patients Undergoing Hematopoietic Stem Cell Transplantation During COVID-19.

BACKGROUND: Healthcare delivery has been significantly changed because of the COVID-19 pandemic. Patients undergoing hematopoietic stem cell transplantation (HSCT) are vulnerable to infections because of their immunocompromised status. The risk of nosocomial infection may be reduced by providing care to patients at home. OBJECTIVES: This article describes one cancer center's approach for delivering safe patient care through homecare encounters, the benefits of home care for HSCT, and future directions. METHODS: Patients received detailed information on home encounters. Advanced practice providers visited patients daily and then returned to the clinic to formulate a plan of care with the interprofessional care team. Transplantation RNs visited patients on the same day to provide the prescribed care. FINDINGS: Based on evaluations from 32 patients and 12 providers, the results indicated that home care was safe, feasible, and beneficial for patient care post-HSCT during the COVID-19 pandemic.
Authors
Liu, J; Allen, DH; Lassiter, M; Cao, F; Sung, AD; Chao, NJ
MLA Citation
Liu, JoAnn, et al. “Homecare Encounters: An Organizational Response to Innovative Care for Patients Undergoing Hematopoietic Stem Cell Transplantation During COVID-19.Clin J Oncol Nurs, vol. 25, no. 4, Aug. 2021, pp. 457–64. Pubmed, doi:10.1188/21.CJON.457-464.
URI
https://scholars.duke.edu/individual/pub1488648
PMID
34269347
Source
pubmed
Published In
Clin J Oncol Nurs
Volume
25
Published Date
Start Page
457
End Page
464
DOI
10.1188/21.CJON.457-464