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:

Professor of Medicine

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

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

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

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Chief, Division of Cell Therapy in the Department of Medicine

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Affiliate of the Regeneration Next Initiative

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:

House calls for stem cell transplant patients during the COVID-19 pandemic.

Authors
Sung, AD; Nichols, KR; Chao, NJ
MLA Citation
Sung, Anthony D., et al. “House calls for stem cell transplant patients during the COVID-19 pandemic.Blood, vol. 136, no. 3, July 2020, pp. 370–71. Pubmed, doi:10.1182/blood.2020006573.
URI
https://scholars.duke.edu/individual/pub1446962
PMID
32488235
Source
pubmed
Published In
Blood
Volume
136
Published Date
Start Page
370
End Page
371
DOI
10.1182/blood.2020006573

Phase I dose escalation study of naive T-cell depleted donor lymphocyte infusion following allogeneic stem cell transplantation.

Prophylactic donor lymphocyte infusions (DLI) are used to augment post-transplant immune recovery to reduce both infectious complications and disease recurrence. Preclinical studies implicate the naive T-cell subset as the primary driver of graft-versus-host disease (GvHD). In this phase I dose escalation study, we assessed the safety of a DLI that was depleted of CD45RA+ naive T cells. Sixteen adult patients received a prophylactic DLI at a median of 113 days (range 76-280 days) following an HLA-identical, non-myeloablative allogeneic hematopoietic stem cell transplantation. Three patients each received the naive T-cell depleted DLI with a CD3+ dose of 1 × 105/kg, 1 × 106/kg, and 5 × 106/kg. The maximum dose of 1 × 107/kg was expanded to 7 patients. No dose-limiting grade III/IV acute GvHD or adverse events attributable to the DLI were observed at any dose level. One patient developed grade 2 acute GvHD of skin and upper intestines, and another developed moderate chronic GvHD of the lungs following the DLI. With a median follow-up of 2.8 years, 2-year progression-free and overall survival is 50.0% and 68.8%, respectively. In conclusion, these data suggest that a DLI that has been depleted of CD45RA+ naive T cells is feasible and carries a low risk of acute or chronic GvHD.
Authors
Maung, KK; Chen, BJ; Barak, I; Li, Z; Rizzieri, DA; Gasparetto, C; Sullivan, KM; Long, GD; Engemann, AM; Waters-Pick, B; Nichols, KR; Lopez, R; Kang, Y; Sarantopoulos, S; Sung, AD; Chao, NJ; Horwitz, ME
MLA Citation
Maung, Ko K., et al. “Phase I dose escalation study of naive T-cell depleted donor lymphocyte infusion following allogeneic stem cell transplantation.Bone Marrow Transplant, July 2020. Pubmed, doi:10.1038/s41409-020-0991-5.
URI
https://scholars.duke.edu/individual/pub1450672
PMID
32624583
Source
pubmed
Published In
Bone Marrow Transplant
Published Date
DOI
10.1038/s41409-020-0991-5

The microbe-derived short-chain fatty acids butyrate and propionate are associated with protection from chronic GVHD.

Studies of the relationship between the gastrointestinal microbiota and outcomes in allogeneic hematopoietic stem cell transplantation (allo-HCT) have thus far largely focused on early complications, predominantly infection and acute graft-versus-host disease (GVHD). We examined the potential relationship of the microbiome with chronic GVHD (cGVHD) by analyzing stool and plasma samples collected late after allo-HCT using a case-control study design. We found lower circulating concentrations of the microbe-derived short-chain fatty acids (SCFAs) propionate and butyrate in day 100 plasma samples from patients who developed cGVHD, compared with those who remained free of this complication, in the initial case-control cohort of transplant patients and in a further cross-sectional cohort from an independent transplant center. An additional cross-sectional patient cohort from a third transplant center was analyzed; however, serum (rather than plasma) was available, and the differences in SCFAs observed in the plasma samples were not recapitulated. In sum, our findings from the primary case-control cohort and 1 of 2 cross-sectional cohorts explored suggest that the gastrointestinal microbiome may exert immunomodulatory effects in allo-HCT patients at least in part due to control of systemic concentrations of microbe-derived SCFAs.
Authors
Markey, KA; Schluter, J; Gomes, ALC; Littmann, ER; Pickard, AJ; Taylor, BP; Giardina, PA; Weber, D; Dai, A; Docampo, MD; Armijo, GK; Slingerland, AE; Slingerland, JB; Nichols, KB; Brereton, DG; Clurman, AG; Ramos, RJ; Rao, A; Bush, A; Bohannon, L; Covington, M; Lew, MV; Rizzieri, DA; Chao, N; Maloy, M; Cho, C; Politikos, I; Giralt, S; Taur, Y; Pamer, EG; Holler, E; Perales, M-A; Ponce, DM; Devlin, SM; Xavier, J; Sung, AD; Peled, JU; Cross, JR; van den Brink, MRM
MLA Citation
Markey, Kate A., et al. “The microbe-derived short-chain fatty acids butyrate and propionate are associated with protection from chronic GVHD.Blood, vol. 136, no. 1, July 2020, pp. 130–36. Pubmed, doi:10.1182/blood.2019003369.
URI
https://scholars.duke.edu/individual/pub1441380
PMID
32430495
Source
pubmed
Published In
Blood
Volume
136
Published Date
Start Page
130
End Page
136
DOI
10.1182/blood.2019003369

Impact of cytogenetic abnormalities on outcomes of adult Philadelphia-negative acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation: a study by the Acute Leukemia Working Committee of the Center for International Blood and

Cytogenetic risk stratification at diagnosis has long been one of the most useful tools to assess prognosis in acute lymphoblastic leukemia (ALL). To examine the prognostic impact of cytogenetic abnormalities on outcomes after allogeneic hematopoietic cell transplantation, we studied 1731 adults with Philadelphia-negative ALL in complete remission who underwent myeloablative or reduced intensity/non-myeloablative conditioning transplant from unrelated or matched sibling donors reported to the Center for International Blood and Marrow Transplant Research. A total of 632 patients had abnormal conventional metaphase cytogenetics. The leukemia-free survival and overall survival rates at 5 years after transplantation in patients with abnormal cytogenetics were 40% and 42%, respectively, which were similar to those in patients with a normal karyotype. Of the previously established cytogenetic risk classifications, modified Medical Research Council-Eastern Cooperative Oncology Group score was the only independent prognosticator of leukemia-free survival (P=0.03). In the multivariable analysis, monosomy 7 predicted post-transplant relapse [hazard ratio (HR)=2.11; 95% confidence interval (95% CI): 1.04-4.27] and treatment failure (HR=1.97; 95% CI: 1.20-3.24). Complex karyotype was prognostic for relapse (HR=1.69; 95% CI: 1.06-2.69), whereas t(8;14) predicted treatment failure (HR=2.85; 95% CI: 1.35-6.02) and overall mortality (HR=3.03; 95% CI: 1.44-6.41). This large study suggested a novel transplant-specific cytogenetic scheme with adverse [monosomy 7, complex karyotype, del(7q), t(8;14), t(11;19), del(11q), tetraploidy/near triploidy], intermediate (normal karyotype and all other abnormalities), and favorable (high hyperdiploidy) risks to prognosticate leukemia-free survival (P=0.02). Although some previously established high-risk Philadelphia-negative cytogenetic abnormalities in ALL can be overcome by transplantation, monosomy 7, complex karyotype, and t(8;14) continue to pose significant risks and yield inferior outcomes.
Authors
Lazaryan, A; Dolan, M; Zhang, M-J; Wang, H-L; Kharfan-Dabaja, MA; Marks, DI; Bejanyan, N; Copelan, E; Majhail, NS; Waller, EK; Chao, N; Prestidge, T; Nishihori, T; Kebriaei, P; Inamoto, Y; Hamilton, B; Hashmi, SK; Kamble, RT; Bacher, U; Hildebrandt, GC; Stiff, PJ; McGuirk, J; Aldoss, I; Beitinjaneh, AM; Muffly, L; Vij, R; Olsson, RF; Byrne, M; Schultz, KR; Aljurf, M; Seftel, M; Savoie, ML; Savani, BN; Verdonck, LF; Cairo, MS; Hossain, N; Bhatt, VR; Frangoul, HA; Abdel-Azim, H; Malki, MA; Munker, R; Rizzieri, D; Khera, N; Nakamura, R; Ringdén, O; van der Poel, M; Murthy, HS; Liu, H; Mori, S; De Oliveira, S; Bolaños-Meade, J; Elsawy, M; Barba, P; Nathan, S; George, B; Pawarode, A; Grunwald, M; Agrawal, V; Wang, Y; Assal, A; Caro, PC; Kuwatsuka, Y; Seo, S; Ustun, C; Politikos, I; Lazarus, HM; Saber, W; Sandmaier, BM; De Lima, M; Litzow, M; Bachanova, V; Weisdorf, D; Acute Leukemia Committee of the CIBMTR,
URI
https://scholars.duke.edu/individual/pub1415328
PMID
31558669
Source
pubmed
Published In
Haematologica
Volume
105
Published Date
Start Page
1329
End Page
1338
DOI
10.3324/haematol.2019.220756

Medical management of acute responses to radiation

Authors
Chao, NJ; Case, C; Confer, D
MLA Citation
Chao, N. J., et al. “Medical management of acute responses to radiation.” Hemasphere, vol. 3, no. S2, June 2019, pp. 164–66. Scopus, doi:10.1097/HS9.0000000000000225.
URI
https://scholars.duke.edu/individual/pub1453133
Source
scopus
Published In
Hemasphere
Volume
3
Published Date
Start Page
164
End Page
166
DOI
10.1097/HS9.0000000000000225