Zhiguo Li

Overview:

survival analysis, dynamic treatment regimes, clinical trials

Positions:

Associate Professor of Biostatistics & Bioinformatics

Biostatistics & Bioinformatics
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2008

University of Michigan, Ann Arbor

Grants:

Validation of a microRNA signature for the prediction, diagnosis and prognosis of acute graft-versus-host disease

Administered By
Immunology
Awarded By
Blood and Marrow Transplant Clinical Trials Network
Role
Biostatistician
Start Date
End Date

Plasma microRNAs as non-invasive biomarker for acute graft-versus-host diseases

Administered By
Immunology
Awarded By
The Biomarker Factory
Role
Investigator
Start Date
End Date

Effects of PPAR agonists on response to immunomodulatory agents in patients with multiple myeloma

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

Effects of PPAR agonists on response to immunomodulatory agents in patients with multiple myeloma

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

Publications:

The impact of bone marrow fibrosis and JAK2 expression on clinical outcomes in patients with newly diagnosed multiple myeloma treated with immunomodulatory agents and/or proteasome inhibitors.

We determined the impact of bone marrow fibrosis (BMF) on the clinical outcomes of newly diagnosed multiple myeloma (NDMM) patients in the current era of myeloma therapy. A total of 393 MM patients were included in the final analysis. The median followup was 83 months (range: 3.9 to 212 months). BMF was noted in 122 (48.2%) evaluable patients. Median progression free survival (PFS) in patients without BMF was 30.2 (95% CI: 24.7-38.0) months, and 21.1 (95% CI: 18.8-27.5) months in patients with BMF present (P = .024). Median overall survival (OS) was 61.2 (95% CI: 51.5-81.2) months in patients without BMF, and 45.1 (95% CI: 38.7-57.0) months in patients with BMF (P = .0048). A subset of 99 patients had their bone marrow biopsies stained for JAK1 and JAK2 by immunohistochemistry. Of these samples 67 (67.7%) patients had detectable JAK2 expression predominantly noted on bone marrow megakaryocytes. JAK2 expression correlated with myeloma disease stage (P = .0071). Our study represents the largest dataset to date examining the association of BMF with prognosis in the era of novel therapies and widespread use of hematopoietic stem cell transplant (HSCT). Our data suggest that MM patients with BMF (particularly those with extensive BMF) have a poorer prognosis even when treated with immunomodulatory agents and proteasome inhibitors.
Authors
Paul, B; Zhao, Y; Loitsch, G; Feinberg, D; Mathews, P; Barak, I; Dupuis, M; Li, Z; Rein, L; Wang, E; Kang, Y
URI
https://scholars.duke.edu/individual/pub1450618
PMID
32628819
Source
pubmed
Published In
Cancer Medicine
Published Date
DOI
10.1002/cam4.3265

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

Microtransplantation in older patients with AML: A pilot study of safety, efficacy and immunologic effects.

Older AML patients have low remission rates and poor survival outcomes with standard chemotherapy. Microtransplantation (MST) refers to infusion of allogeneic hematopoietic stem cells without substantial engraftment. MST has been shown to improve clinical outcomes compared with chemotherapy alone. This is the first trial reporting on broad correlative studies to define immunologic mechanisms of action of MST in older AML patients. Older patients with newly diagnosed AML were eligible for enrollment, receiving induction chemotherapy with cytarabine (100 mg/m2) on days 1-7 and idarubicin (12 mg/m2) on days 1-3 (7 + 3). MST was administered 24 hours later. Patients with complete response (CR) were eligible for consolidation with high dose cytarabine (HiDAC) and a second cycle of MST. Responses were evaluated according to standard criteria per NCCN. Immune correlative studies were performed. Sixteen patients were enrolled and received 7 + 3 and MST (median age 73 years). Nine (56%) had high-risk and seven (44%) had standard-risk cytogenetics. Ten episodes of CRS were observed. No cases of GVHD or treatment-related mortality were reported. Event-free survival (EFS) was 50% at 6 months and 19% at 1 year. Overall survival (OS) was 63% at 6 months and 44% at 1 year. Donor microchimerism was not detected. Longitudinal changes were noted in NGS, TCR sequencing, and cytokine assays. Addition of MST to induction and consolidation chemotherapy was well tolerated in older AML patients. Inferior survival outcomes in our study may be attributed to a higher proportion of very elderly patients with high-risk features. Potential immunologic mechanisms of activity of MST include attenuation of inflammatory cytokines and emergence of tumor-specific T cell clones.
Authors
Sung, AD; Jauhari, S; Siamakpour-Reihani, S; Rao, AV; Staats, J; Chan, C; Meyer, E; Gadi, VK; Nixon, AB; Lyu, J; Xie, J; Bohannon, L; Li, Z; Hourigan, CS; Dillon, LW; Wong, HY; Shelby, R; Diehl, L; de Castro, C; LeBlanc, T; Brander, D; Erba, H; Galal, A; Stefanovic, A; Chao, N; Rizzieri, DA
MLA Citation
Sung, Anthony D., et al. “Microtransplantation in older patients with AML: A pilot study of safety, efficacy and immunologic effects.Am J Hematol, vol. 95, no. 6, June 2020, pp. 662–71. Pubmed, doi:10.1002/ajh.25781.
URI
https://scholars.duke.edu/individual/pub1434771
PMID
32162718
Source
pubmed
Published In
Am J Hematol
Volume
95
Published Date
Start Page
662
End Page
671
DOI
10.1002/ajh.25781

Gamma Gap: A Point-of-Care Test That Correlates With Disease Burden and Treatment Response in Multiple Myeloma.

PURPOSE:We performed a retrospective chart review on 393 patients with multiple myeloma (MM) to determine the utility of the gamma gap (GG). METHODS:We calculated the difference between a patient's total serum protein and albumin as a point-of-care test for assessing disease status in MM. RESULTS:GG is highly correlated with the level of M-spike, and the change in GG correlates with myeloma treatment response. In addition, fitted linear models were established that allow for the calculation of M-protein level from the GG within hours from blood draw. CONCLUSION:Our study has important implications in the care of MM, particularly in countries/areas with limited resources.
Authors
Dupuis, MM; Paul, B; Loitsch, G; Mathews, P; Feinberg, D; Barak, I; Li, Z; Tuchman, SA; Kang, Y
MLA Citation
Dupuis, Megan M., et al. “Gamma Gap: A Point-of-Care Test That Correlates With Disease Burden and Treatment Response in Multiple Myeloma.Jco Oncology Practice, vol. 16, no. 8, Aug. 2020, pp. e751–57. Epmc, doi:10.1200/jop.19.00517.
URI
https://scholars.duke.edu/individual/pub1437138
PMID
32240071
Source
epmc
Published In
Jco Oncology Practice
Volume
16
Published Date
Start Page
e751
End Page
e757
DOI
10.1200/jop.19.00517

The presence of bone marrow fibrosis is associated with poorer prognosis in newly diagnosed multiple myeloma treated with immunomodulatory agents and/or proteasome inhibitors.

Authors
Paul, B; Loitsch, G; Feinberg, D; Barak, I; Li, Z; Wang, E; Zhao, Y; Dupuis, M; Kang, Y
MLA Citation
URI
https://scholars.duke.edu/individual/pub1415025
Source
wos
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
37
Published Date