Scholars@Duke
Zhiguo Li

Zhiguo Li

Associate Professor of Biostatistics & Bioinformatics
Biostatistics & Bioinformatics, Division of Biostatistics
Duke Box 2721, Durham, NC 27710
2424 Erwin Road Ste 1102, 11086 Hock Plaza, Durham, NC 27705

Selected Publications

Analysis of interval censored survival data in sequential multiple assignment randomized trials.

Journal Article Lifetime Data Anal · July 11, 2025 Data analysis methods have been well developed for analyzing data to make inferences about adaptive treatment strategies in sequential multiple assignment randomized trials (SMART), when data are continuous or right-censored. However, in some clinical stud ... Full text Link to item Cite

Isavuconazonium or posaconazole for antifungal prophylaxis in patients with acute myeloid leukemia.

Journal Article J Oncol Pharm Pract · April 2024 BACKGROUND: Invasive fungal infection (IFI) prophylaxis is recommended in patients with acute myeloid leukemia (AML) during induction chemotherapy. Posaconazole (POSA) is the recommended agent of choice; however, this medication can be associated with QTc ... Full text Link to item Cite

Comparison of differing dose levels of methotrexate for patients with primary central nervous system lymphoma.

Journal Article J Oncol Pharm Pract · April 2024 INTRODUCTION: It has long been established that high-dose methotrexate is an essential part of therapy for primary central nervous system lymphoma. When regimens utilizing high-dose methotrexate were first studied, a dose of 8 g/m2 was used. More recently, ... Full text Link to item Cite

Heightened TLR7 signaling primes BCR-activated B cells in chronic graft-versus-host disease for effector functions.

Journal Article Blood Adv · February 13, 2024 Chronic graft-versus-host disease (cGVHD) is a debilitating, autoimmune-like syndrome that can occur after allogeneic hematopoietic stem cell transplantation. Constitutively activated B cells contribute to ongoing alloreactivity and autoreactivity in patie ... Full text Open Access Link to item Cite

The TLR2/TLR6 ligand FSL-1 mitigates radiation-induced hematopoietic injury in mice and nonhuman primates.

Journal Article Proc Natl Acad Sci U S A · December 12, 2023 Thrombocytopenia, hemorrhage, anemia, and infection are life-threatening issues following accidental or intentional radiation exposure. Since few therapeutics are available, safe and efficacious small molecules to mitigate radiation-induced injury need to ... Full text Link to item Cite

Temporary Knockdown of p53 During Focal Limb Irradiation Increases the Development of Sarcomas.

Journal Article Cancer Res Commun · December 5, 2023 UNLABELLED: Approximately half of patients with cancer receive radiotherapy and, as cancer survivorship increases, the low rate of radiation-associated sarcomas is rising. Pharmacologic inhibition of p53 has been proposed as an approach to ameliorate acute ... Full text Link to item Cite

A Phase I Trial of SYK Inhibition with Fostamatinib in the Prevention and Treatment of Chronic Graft-Versus-Host Disease.

Journal Article Transplant Cell Ther · March 2023 Despite the exciting advancement of novel therapies, chronic graft-versus-host disease (cGVHD) remains the most common cause of non-relapse mortality after allogeneic hematopoietic stem cell transplantation (HCT). Frontline treatment of cGVHD involves syst ... Full text Link to item Cite

Phase I study of opaganib, an oral sphingosine kinase 2-specific inhibitor, in relapsed and/or refractory multiple myeloma.

Journal Article Ann Hematol · February 2023 Multiple myeloma (MM) remains an incurable disease and there is an unmet medical need for novel therapeutic drugs that do not share similar mechanisms of action with currently available agents. Sphingosine kinase 2 (SK2) is an innovative molecular target f ... Full text Link to item Cite

PPAR agonists attenuate lenalidomide's anti-myeloma activity in vitro and in vivo.

Journal Article Cancer Lett · October 1, 2022 Many patients with multiple myeloma (MM) have comorbidities and are treated with PPAR agonists. Immunomodulatory agents (IMiDs) are the cornerstones for MM therapy. Currently, little is known about how co-administration of PPAR agonists impacts lenalidomid ... Full text Link to item Cite

Re-Examination of the Exacerbating Effect of Inflammasome Components during Radiation Injury.

Journal Article Radiat Res · February 1, 2022 Radiation can be applied for therapeutic benefit against cancer or may result in devastating harm due to accidental or intentional release of nuclear energy. In all cases, radiation exposure causes molecular and cellular damage, resulting in the production ... Full text Link to item Cite

Targeting Glycolysis in Alloreactive T Cells to Prevent Acute Graft-Versus-Host Disease While Preserving Graft-Versus-Leukemia Effect.

Journal Article Front Immunol · 2022 Alloreactive donor T cells undergo extensive metabolic reprogramming to become activated and induce graft-versus-host disease (GVHD) upon alloantigen encounter. It is generally thought that glycolysis, which promotes T cell growth and clonal expansion, is ... Full text Link to item Cite

Alphavirus Replicon Particle Vaccine Breaks B Cell Tolerance and Rapidly Induces IgG to Murine Hematolymphoid Tumor Associated Antigens.

Journal Article Front Immunol · 2022 De novo immune responses to myeloid and other blood-borne tumors are notably limited and ineffective, making our ability to promote immune responses with vaccines a major challenge. While focus has been largely on cytotoxic cell-mediated tumor eradication, ... Full text Open Access Link to item Cite

Trial in Progress: A Phase 2 Single Arm, Multicenter Trial to Evaluate the Efficacy of the BiTE ® Antibody Blinatumomab (Blincyto) and Vincristine Sulfate Liposomal Injection (Marqibo) in Adult Subjects with Relapsed/Refractory Philadelphia Negative CD19+ Acute Lymphoblastic Leukemia

Conference Blood · November 5, 2021 AbstractBackground: Relapsed Acute Lymphoblastic Leukemia (ALL) is not curable with standard therapies. Effective outpatient treatment, allowing patients to maintain a good quality of life, while offering a ... Full text Cite

Phase II Study of Single-Agent and Combination Everolimus and Panobinostat in Relapsed or Refractory Diffuse Large B-Cell Lymphoma.

Journal Article Cancer Invest · November 2021 Novel therapeutics are needed for patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). Everolimus is an mTOR pathway inhibitor with synergistic anti-tumor activity when combined with histone deacetylase inhibitors, such as panobi ... Full text Link to item Cite

BAFF promotes heightened BCR responsiveness and manifestations of chronic GVHD after allogeneic stem cell transplantation.

Journal Article Blood · May 6, 2021 Patients with chronic graft-versus-host disease (cGVHD) have increased B cell-activating factor (BAFF) levels, but whether BAFF promotes disease after allogeneic bone marrow transplantation (allo-BMT) remains unknown. In a major histocompatibility complex- ... Full text Link to item Cite

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

Journal Article Bone Marrow Transplant · January 2021 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-ho ... Full text Link to item Cite

Morphologic Leukemia-Free State in Acute Myeloid Leukemia Is Sufficient for Successful Allogeneic Hematopoietic Stem Cell Transplant

Conference Blood · November 5, 2020 Allogeneic hematopoietic cell transplant (HCT) improves survival in patients with relapsed or high risk acute myeloid leukemia (AML). Complete remission (CR) is typically a pre-requisite for transplantation, though many do not achieve a formal CR. ... Full text Cite

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

Journal Article JCO oncology practice · August 2020 PurposeWe performed a retrospective chart review on 393 patients with multiple myeloma (MM) to determine the utility of the gamma gap (GG).MethodsWe calculated the difference between a patient's total serum protein and albumin as a point- ... Full text Cite

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.

Journal Article Cancer Med · August 2020 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 w ... Full text Link to item Cite

Fibrinogen-Coated Albumin Nanospheres Prevent Thrombocytopenia-Related Bleeding.

Journal Article Radiat Res · August 1, 2020 Thrombocytopenia (TCP) may cause severe and life-threatening bleeding. While this may be prevented by platelet transfusions, transfusions are associated with potential complications, do not always work (platelet refractory) and are not always available. Th ... Full text Link to item Cite

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

Journal Article Am J Hematol · June 2020 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 ... Full text Link to item Cite

Evaluation of the Oral SYK Inhibitor Fostamatinib in Patients after Allogeneic Transplantation for Chronic Graft-Versus-Host Disease

Conference Blood · November 13, 2019 Our group previously showed that B cells signal aberrantly through the B cell receptor (BCR) in allogeneic hematopoietic stem cell transplant (HCT) patients with active chronic graft-versus-host disease (cGVHD). Preclinical mouse studies have demon ... Full text Cite

Incidence of Invasive Fungal Infections in Acute Leukemia Patients Utilizing Micafungin Prophylaxis Compared to Second-Generation Azole Prophylaxis

Conference Blood · November 13, 2019 Introduction/Background:Standard therapy for both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) is myelosuppressive, and patients are expected to be neutropenic for a prolonged period. Due to t ... Full text Cite

Efficient estimation of grouped survival models.

Journal Article BMC Bioinformatics · May 28, 2019 BACKGROUND: Time- and dose-to-event phenotypes used in basic science and translational studies are commonly measured imprecisely or incompletely due to limitations of the experimental design or data collection schema. For example, drug-induced toxicities a ... Full text Link to item Cite

Sample size calculation for studies with grouped survival data.

Journal Article Stat Med · November 30, 2018 Grouped survival data arise often in studies where the disease status is assessed at regular visits to clinic. The time to the event of interest can only be determined to be between two adjacent visits or is right censored at one visit. In data analysis, r ... Full text Open Access Link to item Cite

Phase I Study of the Combination of Bendamustine, Rituximab, and Pixantrone in Patients With Relapsed/Refractory B-cell Non-Hodgkin Lymphoma.

Journal Article Clin Lymphoma Myeloma Leuk · October 2018 BACKGROUND: For patients with aggressive lymphomas who relapse after initial therapy, a durable response is rarely achieved with standard salvage therapies. Significant efforts have focused on the development of novel treatments with reduced toxicity. We c ... Full text Link to item Cite

Late Gastrointestinal Complications of Allogeneic Hematopoietic Stem Cell Transplantation in Adults.

Journal Article Biol Blood Marrow Transplant · April 2018 Gastrointestinal (GI) complications including graft-versus-host disease (GVHD) are a major cause of morbidity and mortality in allogenic stem transplant recipients. Although several studies have previously looked into the acute GI complications, fewer smal ... Full text Link to item Cite

High-dose BCNU/Melphalan conditioning regimen before autologous stem cell transplantation in newly diagnosed multiple myeloma.

Journal Article Bone Marrow Transplant · January 2018 Single-agent high-dose melphalan (HDM, 200 mg/m2) has been the most commonly used conditioning regimen prior to autologous stem cell transplant, since its introduction in 1992. We used a more aggressive alkylator-based conditioning regimen in an attempt to ... Full text Link to item Cite

Facilitating the Calculation of the Efficient Score Using Symbolic Computing.

Journal Article Am Stat · 2018 The score statistic continues to be a fundamental tool for statistical inference. In the analysis of data from high-throughput genomic assays, inference on the basis of the score usually enjoys greater stability, considerably higher computational efficienc ... Full text Link to item Cite

Phase I/II dose expansion of a trial investigating bendamustine and pomalidomide with dexamethasone (BPd) in patients with relapsed/refractory multiple myeloma.

Conference Journal of Clinical Oncology · May 20, 2017 8008 Background: The combination of bendamustine, pomalidomide, and dexamethasone (BPd) displays promising activity in heavily pretreated RRMM. In the Phase I portion, MTD was 120 mg/m2bendamustine/3mg pomali ... Full text Cite

Phase II study of dose-attenuated bortezomib, cyclophosphamide and dexamethasone ("VCD-Lite") in very old or otherwise toxicity-vulnerable adults with newly diagnosed multiple myeloma.

Journal Article J Geriatr Oncol · May 2017 OBJECTIVES: Multiple myeloma (MM) primarily strikes older adults, but full-dose chemotherapy such as bortezomib (Velcade), cyclophosphamide and dexamethasone (VCD) is often excessively toxic to very old or frail adults and those with substantial comorbidit ... Full text Link to item Cite

Comparison of adaptive treatment strategies based on longitudinal outcomes in sequential multiple assignment randomized trials.

Journal Article Stat Med · February 10, 2017 In sequential multiple assignment randomized trials, longitudinal outcomes may be the most important outcomes of interest because this type of trials is usually conducted in areas of chronic diseases or conditions. We propose to use a weighted generalized ... Full text Link to item Cite

Outcomes of Maintenance Therapy with Bortezomib after Autologous Stem Cell Transplantation for Patients with Multiple Myeloma.

Journal Article Biol Blood Marrow Transplant · February 2017 Comprehensive recommendations for maintenance therapy after autologous stem cell transplantation (ASCT) for patients with multiple myeloma (MM) have yet to be defined. Bortezomib has been utilized as maintenance therapy after ASCT, but data attesting to th ... Full text Link to item Cite

Recipient-Derived BAFF and Alloantigen Synergistically Activate B Cells in Murine Chronic Gvhd

Conference Blood · December 2, 2016 AbstractIncreased B cell-activating factor (BAFF) and aberrant B cell survival and activation are associated with chronic graft versus host disease (cGVHD) in patients. Whether excessive BAFF production has ... Full text Cite

All-Trans Retinoic Acid (ATRA) Targets IRF4 Deficient, NOTCH2-Activated B Cells from Chronic Gvhd Patients

Conference Blood · December 2, 2016 AbstractAllogeneic hematopoietic stem cell transplantation (HCT)-related immune pathology severely limits patient (Pt) survival, largely due to infections. Chronic graft versus host disease (cGVHD) Pts are p ... Full text Cite

Plerixafor (a CXCR4 antagonist) following myeloablative allogeneic hematopoietic stem cell transplantation enhances hematopoietic recovery.

Journal Article J Hematol Oncol · August 17, 2016 BACKGROUND: The binding of CXCR4 with its ligand (stromal-derived factor-1) maintains hematopoietic stem/progenitor cells (HSPCs) in a quiescent state. We hypothesized that blocking CXCR4/SDF-1 interaction after hematopoietic stem cell transplantation (HSC ... Full text Open Access Link to item Cite

Fitting Cox Models with Doubly Censored Data Using Spline-Based Sieve Marginal Likelihood.

Journal Article Scand Stat Theory Appl · June 2016 In some applications, the failure time of interest is the time from an originating event to a failure event, while both event times are interval censored. We propose fitting Cox proportional hazards models to this type of data using a spline-based sieve ma ... Full text Link to item Cite

Rad18 confers hematopoietic progenitor cell DNA damage tolerance independently of the Fanconi Anemia pathway in vivo.

Journal Article Nucleic Acids Res · May 19, 2016 In cultured cancer cells the E3 ubiquitin ligase Rad18 activates Trans-Lesion Synthesis (TLS) and the Fanconi Anemia (FA) pathway. However, physiological roles of Rad18 in DNA damage tolerance and carcinogenesis are unknown and were investigated here. Prim ... Full text Open Access Link to item Cite

Regulation of T cell function by microRNA-720.

Journal Article Sci Rep · July 22, 2015 Chronic hepatitis B virus (HBV) infection is a major global health burden. Functional exhaustion and numerical reduction of HBV-specific cytotoxic T lymphocytes (CTLs) in the liver and peripheral blood limit anti-HBV CTL activity in patients with chronic H ... Full text Link to item Cite

Cyclophosphamide-based hematopoietic stem cell mobilization before autologous stem cell transplantation in newly diagnosed multiple myeloma.

Journal Article J Clin Apher · June 2015 High-dose cyclophosphamide (Cy) is frequently employed for peripheral blood mobilization of hematopoietic stem cells before high-dose chemotherapy with autologous stem cell transplantation (ASCT) in multiple myeloma (MM). The benefit of mobilization with C ... Full text Link to item Cite

Late Gastrointestinal Complications of Allogeneic Hematopoietic Stem Cell Transplantation

Conference Biology of Blood and Marrow Transplantation · February 2015 Full text Cite

A global logrank test for adaptive treatment strategies based on observational studies.

Journal Article Stat Med · February 28, 2014 In studying adaptive treatment strategies, a natural question that is of paramount interest is whether there is any significant difference among all possible treatment strategies. When the outcome variable of interest is time-to-event, we propose an invers ... Full text Link to item Cite

Reduced-intensity allogeneic transplantation using alemtuzumab from HLA-matched related, unrelated, or haploidentical related donors for patients with hematologic malignancies.

Journal Article Biol Blood Marrow Transplant · February 2014 We present a comparative study on 124 patients with hematologic malignancies who had undergone reduced-intensity conditioning and then received a transplant from an HLA-matched related (MRD), an HLA-matched unrelated (MUD), or an HLA-haploidentical related ... Full text Link to item Cite

Plasma microRNA signature as a noninvasive biomarker for acute graft-versus-host disease.

Journal Article Blood · November 7, 2013 Acute graft-versus-host disease (aGVHD) is the leading cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Approximately 35% to 50% of HCT recipients develop aGVHD; however, there are no validated diagnostic and pred ... Full text Link to item Cite

Upregulation of IL-1β, IL-6, and CCL-2 by a novel mouse model of pancreatic ischemia-reperfusion injury.

Journal Article Transplantation · April 27, 2013 BACKGROUND: Little is known about the immunologic events surrounding pancreatic ischemia-reperfusion injury (IRI) because of a lack of established experimental models. The purpose of this study was to develop a mouse model for pancreatic IRI to serve as a ... Full text Link to item Cite

Insulin-like growth factor 1 mitigates hematopoietic toxicity after lethal total body irradiation.

Journal Article Int J Radiat Oncol Biol Phys · March 15, 2013 PURPOSE: To investigate whether and how insulin-like growth factor 1 (IGF-1) mitigates hematopoietic toxicity after total body irradiation. METHODS AND MATERIALS: BALB/c mice were irradiated with a lethal dose of radiation (7.5 Gy) and treated with IGF-1 a ... Full text Link to item Cite

Re-induction therapy decisions based on day 14 bone marrow biopsy in acute myeloid leukemia.

Journal Article Leuk Res · January 2013 PURPOSE: The decision to re-induce patients with acute myeloid leukemia (AML) based on results of the day 14 bone marrow (BM) biopsy is variable and lacks evidence based data. The aim of our review was to evaluate the accuracy of a day 14 BM biopsy in dete ... Full text Link to item Cite

Heparan sulfate, an endogenous TLR4 agonist, promotes acute GVHD after allogeneic stem cell transplantation.

Journal Article Blood · October 4, 2012 Graft-versus-host disease (GVHD) remains the most common cause of nonrelapse-related morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although T-cell depletion and intensive immunosuppression are effective in th ... Full text Link to item Cite

Power and sample size calculations for SNP association studies with censored time-to-event outcomes.

Journal Article Genet Epidemiol · September 2012 For many clinical studies in cancer, germline DNA is prospectively collected for the purpose of discovering or validating single-nucleotide polymorphisms (SNPs) associated with clinical outcomes. The primary clinical endpoint for many of these studies are ... Full text Link to item Cite

Outcomes of a 1-day nonmyeloablative salvage regimen for patients with primary graft failure after allogeneic hematopoietic cell transplantation.

Journal Article Bone Marrow Transplant · May 2012 Primary graft failure after allogeneic hematopoietic cell transplantation is a life-threatening complication. A shortened conditioning regimen may reduce the risk of infection and increase the chance of survival. Here, we report the outcome of 11 patients ... Full text Link to item Cite

Phase II study of cenersen, an antisense inhibitor of p53, in combination with fludarabine, cyclophosphamide and rituximab for high-risk chronic lymphocytic leukemia.

Journal Article Leuk Lymphoma · February 2012 Patients with chronic lymphocytic leukemia (CLL) with deletion or mutation of TP53 have exceedingly poor clinical outcomes. Cenersen, an oligonucleotide targeting TP53, has been shown to abrogate the activity of TP53 gain-of-function mutants and to increas ... Full text Link to item Cite

Emergent anxiety after antidepressant initiation: a retrospective cohort study of Veterans Affairs Health System patients with depression.

Journal Article Clin Ther · December 2011 BACKGROUND: Initiation of antidepressant treatment for depression may be associated with new onset (emergent) anxiety. OBJECTIVE: The purpose of this study was to assess demographic and clinical factors associated with emergent anxiety following a new anti ... Full text Link to item Cite

Relative risk regression for current status data in case-cohort studies

Journal Article Canadian Journal of Statistics · December 1, 2011 We propose using the weighted likelihood method to fit a general relative risk regression model for the current status data with missing data as arise, for example, in case-cohort studies. The missingness probability is either known or can be reasonably es ... Full text Cite

Sample size formulae for two-stage randomized trials with survival outcomes.

Journal Article Biometrika · September 2011 Two-stage randomized trials are growing in importance in developing adaptive treatment strategies, i.e. treatment policies or dynamic treatment regimes. Usually, the first stage involves randomization to one of the several initial treatments. The second st ... Full text Link to item Cite

Hematopoietic cell infusion for the treatment of nuclear disaster victims: new data from the Chernobyl accident.

Journal Article Int J Radiat Biol · August 2011 PURPOSE: To present previously unavailable data on the use of stem cell administration to aid recovery of victims of the Chernobyl disaster. On 26 April 1986, an accident at Unit 4 of the Chernobyl Nuclear Power Plant took place during the planned test of ... Full text Link to item Cite

Feasibility of low-dose interleukin-2 therapy following T-cell-depleted nonmyeloablative allogeneic hematopoietic stem cell transplantation from HLA-matched or -mismatched family member donors.

Journal Article Cancer Invest · January 2011 INTRODUCTION: High relapse rates and infections remain primary causes of failure in nonmyeloablative transplantation. Interleukin-2 (IL-2) may stimulate the immune system and improve outcomes. The primary objective of this pilot study was to evaluate the f ... Full text Link to item Cite

Construction of confidence intervals and regions for ordered binomial probabilities

Journal Article American Statistician · November 1, 2010 In biomedical studies and other areas, there are often situations where parameters are known to be ordered. In these situations, incorporating the order restriction can produce much more efficient estimates than ignoring it. There is much research on point ... Full text Cite

Weighted likelihood method for grouped survival data in case-cohort studies with application to HIV vaccine trials.

Journal Article Biometrics · December 2008 Grouped failure time data arise often in HIV studies. In a recent preventive HIV vaccine efficacy trial, immune responses generated by the vaccine were measured from a case-cohort sample of vaccine recipients, who were subsequently evaluated for the study ... Full text Link to item Cite

Analysis on binary responses with ordered covariates and missing data.

Journal Article Stat Med · August 15, 2007 We consider the situation of two ordered categorical variables and a binary outcome variable, where one or both of the categorical variables may have missing values. The goal is to estimate the probability of response of the outcome variable for each cell ... Full text Link to item Cite

Comparing an experimental agent to a standard agent: relative merits of a one-arm or randomized two-arm Phase II design.

Journal Article Clin Trials · 2006 BACKGROUND: Phase II clinical trials in cancer are used to assess whether a new agent has sufficiently promising efficacy to proceed on to a larger definitive study comparing the new agent to a standard agent. PURPOSE: A crucial issue in determining the us ... Full text Link to item Cite