Vu Duong - Academia.edu (original) (raw)

Papers by Vu Duong

Biology

The prognostic significance of the length of internal tandem duplication (ITD) insertions in muta... more The prognostic significance of the length of internal tandem duplication (ITD) insertions in mutant FLT3 genes in acute myeloid leukemia (AML) is controversial. We conducted a retrospective study to evaluate the correlation between the ITD base-pair (bp) insertion length and clinical outcomes. The mutational status of the FLT3 gene was evaluated in 402 of 467 consecutive AML patients treated at the University of Maryland Greenebaum Comprehensive Cancer Center between 2013 and 2020; 77 had FLT3-ITD mutations. Patients were divided into three cohorts based on bp insertion length (<30 (0–33rd percentile), 30–53 (34th–66th percentile),and >53 (>66th percentile)). The median overall survival (OS) of patients was 16.5 months (confidence interval (CI) 7.3-NA), 18.5 months (CI 7.3-NA), and 21.9 months (CI 19.1-NA) (p = 0.03) for the <30, 30–53, and >53 bp insertion length cohorts, respectively. The adjusted median event-free survival (EFS) for the ITD insertion lengths >30...

Cureus, 2020

Clinicians have continued to report on the clinical behavior and characteristics of patients with... more Clinicians have continued to report on the clinical behavior and characteristics of patients with coronavirus disease 2019 (COVID-19) as our knowledge of the virus continues to mature. Herein, we report the case of a 39-year-old male with multiple comorbidities who became critically ill with COVID-19 infection, requiring mechanical ventilation and vasopressors, and then developed agranulocytosis following clinical improvement and resolution of symptoms of COVID infection. The period of agranulocytosis coincided with the development of thrombocytosis, and following resolution of agranulocytosis, the platelet count also normalized, suggesting a possible related mechanism. Interestingly, the patient was treated with TBO-filgrastim 480 mcg daily with a rapid reconstitution of neutrophils. While the mechanism of agranulocytosis remains unknown, we report, to our knowledge, the first known case of agranulocytosis following COVID-19 infection and its successful treatment with granulocyte colony-stimulating factor.

Agriculture, 2021

Rice breeding was conducted for a long time during historical times and is an important job in Vi... more Rice breeding was conducted for a long time during historical times and is an important job in Vietnam because rice is the major food for domestic consumption and export. In this review, we have provided a comprehensive insight into the importance of promising rice germplasm resources, breeding achievements, and breeding approaches as well as discussed challenges and perspectives of rice breeding in this country. With rice germplasm and wild rice relative resources with rich and various genetic diversity, their useful genes and traits have been exploited and integrated into commercial varieties as the final outputs of rice breeding programs. New achievements of the modern genetics era have been approached and effectively contributed to breeding activities in this country. Genome sequences, molecular breeding, and mutation are powerful tools and playing vital roles in developing new varieties with characteristics of interest that should be followed by the current market demands. In t...

Biology, 2021

The significance of FLT3-ITD in acute promyelocytic leukemia (APL) is not well-established. We pe... more The significance of FLT3-ITD in acute promyelocytic leukemia (APL) is not well-established. We performed a bi-center retrospective study of 138 APL patients, 59 (42.8%) of whom had FLT3-ITD. APL patients with FLT3-ITD had higher baseline white blood cell counts (WBCs) (p < 0.001), higher hemoglobin, (p = 0.03), higher aspartate aminotransferase (p = 0.001), lower platelets (p = 0.004), lower fibrinogen (p = 0.003), and higher incidences of disseminated intravascular coagulation (p = 0.005), M3v variant morphology (p < 0.001), and the bcr3 isoform (p < 0.001). FLT3-ITD was associated with inferior post-consolidation complete remission (CR) (p = 0.02) and 5-year overall survival (OS) of 79.7%, compared to 94.4% for FLT3-WT (wild-type) (p = 0.02). FLT3-ITD was strongly associated with baseline WBCs ≥ 25 × 109/L (odds ratio (OR): 54.4; 95% CI: 10.4–286.1; p < 0.001). High FLT3-ITD allelic burdens correlated with high-risk (HR) Sanz scores and high WBCs, with every 1% increas...

Pharmaceuticals, 2020

Outcomes of acute lymphoblastic leukemia (ALL) in older adults treated with chemotherapy are poor... more Outcomes of acute lymphoblastic leukemia (ALL) in older adults treated with chemotherapy are poor. The CD19/CD3 bispecific T-cell engager (BiTE) antibody blinatumomab is approved for refractory, relapsed or minimal/measurable residual disease (MRD)-positive B-cell ALL, but there is little experience in the upfront setting, including in older patients. We retrospectively analyzed outcomes of blinatumomab monotherapy in five newly diagnosed Philadelphia chromosome-negative B-cell ALL patients over 70 years. Three had cytokine release syndrome, treated with dexamethasone and/or tocilizumab, and four patients had neurotoxicity, treated with dexamethasone, without blinatumomab interruption. All five achieved complete remission (CR) after cycle one, three with undetectable MRD. All five were alive at 8 to 15 months. Three remained in MRD-negative CR. Two relapsed after cycle 3, one with extramedullary disease. In our small cohort of patients over 70 years, blinatumomab was safe initial th...

Agriculture, 2020

Salinity stress is one of the most severe constraints limiting rice production worldwide. Thus, t... more Salinity stress is one of the most severe constraints limiting rice production worldwide. Thus, the development of salt-tolerant rice promises to deal with increasing food demand due to climate change effects. This study investigated the salinity tolerance of mutant rice by evaluating phenotype and genotype, using forty-two simple sequence repeat (SSR) markers linked to the salinity tolerance Saltol quantitative trait locus (QTL) in ten cultivars and mutant lines. Results of phenotypic screening showed that the mutant line SKLo/BC15TB and cultivar BC15TB performed salt tolerance, while the mutant line Bao Thai/DT 84 and cultivar DT84DB were sensitive to salt stress. The markers RM 493, RM 562, RM 10748, RM 518, RM 237, and RM 20224 were the most polymorphic in salinity tolerance. Among them, RM 237, RM 10748, and RM 224 showed the highest polymorphism information (PIC = 0.58). This study reveals that the three markers are profitable for classification of salinity tolerance in both c...

Journal of Clinical Oncology, 2013

7049 Background: FLT3-ITD mutations are present in AML in 30% of patients, most commonly with a n... more 7049 Background: FLT3-ITD mutations are present in AML in 30% of patients, most commonly with a normal karyotype, and are associated with short disease-free survival. In vitro and in vivo studies of FLT3-ITD cell lines and patient samples have demonstrated DNA double-strand break repair by an alternative highly error-prone form of non-homologous end-joining (ALT NHEJ), resulting in illegitimate ligation of non-contiguous DNA breaks, causing DNA deletions and translocations that may contribute to disease progression. To look for clinical evidence of genomic instability, we reviewed cytogenetic changes at relapse. Methods: Charts of patients with cytogenetically normal AML with FLT3-ITD treated at the University of Maryland Greenebaum Cancer Center were reviewed along with metaphase analysis results at diagnosis and relapse. Results: Cytogenetic data were available from first and, when applicable, subsequent relapses for 12 patients with cytogenetically normal AML with FLT3-ITD who re...

Journal of Clinical Oncology, 2012

2099 Background: Primary central nervous system lymphoma (PCNSL) is a rare aggressive variant of ... more 2099 Background: Primary central nervous system lymphoma (PCNSL) is a rare aggressive variant of diffuse large B cell lymphoma (DLBCL) with a poor prognosis. Optimal therapeutic strategies have not yet been defined. High dose methotrexate (HD MTX) is an effective chemotherapeutic agent with superior outcomes compared to historical studies using whole brain radiation therapy (WBRT). Purpose: To review clinicopathologic characteristics, therapy and outcomes of 54 patients (pts) with primary CNS DLBCL. Methods: This was a single center retrospective review of pts with confirmed diagnosis of primary CNS DLBCL from 1999 to 2009. Data was extracted from the Moffitt Cancer Center (MCC) electronic records. Baseline demographics, clinical, pathological and treatment data were collected and analyzed. Pts were stratified according to their treatment regimens including HD MTX (8g/m2) alone or in combinations and WBRT alone or in combination with CT. Descriptive statistical analyses were utilize...

$Research paper thumbnail of Comparison of High-Dose Cytarabine, Mitoxantrone, and Pegaspargase (HAM-pegA) to High-Dose Cytarabine, Mitoxantrone, Cladribine, and Filgrastim (CLAG-M) as First-Line Salvage Cytotoxic Chemotherapy for Relapsed/Refractory Acute Myeloid Leukemia$

Journal of Clinical Medicine, 2020

Currently, no standard of care exists for the treatment of relapsed or refractory acute myeloid l... more Currently, no standard of care exists for the treatment of relapsed or refractory acute myeloid leukemia (AML). We present our institutional experience with using either CLAG-M or HAM-pegA, a novel regimen that includes pegaspargase. This is a retrospective comparison of 34 patients receiving CLAG-M and 10 receiving HAM-pegA as first salvage cytotoxic chemotherapy in the relapsed or refractory setting. Composite complete response rates were 47.1% for CLAG-M and 90% for HAM-pegA (p = 0.027). Event-free survival was significantly different in favor of HAM-pegA (p = 0.045), though overall survival was similar between groups. There were no significant differences in toxicities experienced by patients treated with the two regimens, including adverse events of special interest related to pegaspargase (venous thromboembolism, hemorrhage, hepatotoxicity, pancreatitis, and hypersensitivity reactions). HAM-pegA is a novel regimen for relapsed or refractory AML that resulted in improved respon...

European Journal of Nuclear Medicine and Molecular Imaging, 2019

Purpose Peptide receptor radionuclide/chemoradionuclide therapy (PRRT/PRCRT) is an effective ther... more Purpose Peptide receptor radionuclide/chemoradionuclide therapy (PRRT/PRCRT) is an effective therapy for metastatic neuroendocrine neoplasia (NEN), but therapy-related myeloid neoplasms (t-MN) remain of concern. The study reviewed the clinicopathological features and outcomes of patients who developed t-MN. Methods Retrospective analysis of all patients diagnosed with t-MN by 2016 WHO classification, from a cohort of 521 patients who received PRRT/PRCRT over a 12-year period. Molecular next-generation sequencing using an in-house 26-gene panel was performed. Results Twenty-five of 521 (4.8%) patients were diagnosed with t-MN, including six acute myeloid leukaemia (AML) and 19 myelodysplastic syndrome (MDS). The median time from first cycle PRRT/PRCRT to diagnosis of t-MN was 26 months (range 4-91). Twenty-two of 25 (88%) patients had grade 1-2 pancreatic or small bowel NEN with moderate metastatic liver burden. Six patients (24%) had prior chemotherapy. Median number of PRRT cycles = 5 (22/25 (88%) with concomitant radiosensitising chemotherapy). All 25 patients achieved disease stabilisation (68%) or partial response (32%) on RECIST 1.1 at 3 months post-PRRT. At t-MN diagnosis, all patients presented with thrombocytopenia (median nadir 33 × 10 9 /L, range 3-75) and 17 (68%) remained NEN progression-free. Marrow genetic analysis revealed unfavourable karyotype in 16/25 (66%) patients with tumour protein 53 (TP53) mutation in nine (36%). Azacitidine therapy was utilised in ten eligible patients, while four received induction chemotherapy for AML. The median overall survival from first PRRT was 62 months (19-94), but from t-MN diagnosis was only 13 months (1-56), with death due primarily to haematological disease progression. Conclusions The diagnosis of t-MN after PRRT/PRCRT is an infrequent but serious complication with poor overall survival. Most patients present with thrombocytopenia; unfavourable genetic mutations have a poor response to t-MN treatment. Prospective data are needed to explore potential pre-existing genetic factors and predictive biomarkers to minimise the risk of t-MN. Keywords 177 Lu-DOTATATE. Pepetide receptor radionuclide therapy. Neuroendocrine neoplasm. Therapy-related myeloid neoplasm. Myelodysplasia. Acute myeloid leukaemia This article is part of the Topical Collection on Oncology-Digestive Tract.

Leukemia & lymphoma, Jan 11, 2018

Journal of hematopathology, Sep 1, 2018

We describe two patients with acute promyelocytic leukemia (APL) with an unusual immunophenotype ... more We describe two patients with acute promyelocytic leukemia (APL) with an unusual immunophenotype with co-expression of myeloperoxidase (MPO) with cytoplasmic CD3 (cCD3) representing myeloid and T-lineage differentiation. Both harbored -ITD mutations. One additionally had a deletion in the gene affecting the primer binding site, thus limiting measurable residual disease (MRD) analysis during follow-up. Both patients achieved durable remission with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO)-based therapy, thus mitigating the need for repetitive conventional chemotherapy cycles and allogeneic stem cell transplantation. Our report highlights the complexity and challenge of diagnosis and management of APL due to the variant immunophenotype and genetics, and underscores the importance of synthesizing information from all testing modalities. The association of the unusual immunophenotype and -ITD mutation illustrates the plasticity of the hematopoietic stem cell and the path...

The Journal of infectious diseases, Jan 12, 2018

Nontyphoidal Salmonella (NTS) organisms are a major cause of gastroenteritis and bacteremia, but ... more Nontyphoidal Salmonella (NTS) organisms are a major cause of gastroenteritis and bacteremia, but little is known about maternally acquired immunity and natural exposure in infant populations residing in areas where NTS disease is highly endemic. We recruited 503 pregnant mothers and their infants (following delivery) from urban areas in Vietnam and followed infants until they were 1 year old. Exposure to the dominant NTS serovars, Salmonella enterica serovars Typhimurium and Enteritidis, were assessed using lipopolysaccharide (LPS) O antigen-specific antibodies. Antibody dynamics, the role of maternally acquired antibodies, and NTS seroincidence rates were modeled using multivariate linear risk factor models and generalized additive mixed-effect models. Transplacental transfer of NTS LPS-specific maternal antibodies to infants was highly efficient. Waning of transplacentally acquired NTS LPS-specific antibodies at 4 months of age left infants susceptible to Salmonella organisms, aft...

American journal of leukemia research, 2018

Relapsed Philadelphia chromosome (Ph) positive Acute Lymphoblastic Leukemia (ALL) is an aggressiv... more Relapsed Philadelphia chromosome (Ph) positive Acute Lymphoblastic Leukemia (ALL) is an aggressive lymphoid malignancy with a poor prognosis and no randomized studies demonstrating superiority of any single salvage regimen. We present the case of a 33-year-old woman with relapsed Ph positive precursor (pre) B-cell ALL with rapidly rising peripheral blasts while on blinatumomab monotherapy initially, but ultimately responded with the addition of Vincristine Sulfate Liposome Injection (VSLI). Ponatinib was added later when it became available for the patient, and she ultimately achieved a complete remission. Further study is warranted to explore mechanisms of potential synergy, and the safety and efficacy of the combination of blinatumomab and VSLI.

$Research paper thumbnail of Asparaginase Erwinia chrysanthemi effectively depletes plasma glutamine in adult patients with relapsed/refractory acute myeloid leukemia$

Cancer chemotherapy and pharmacology, Jan 8, 2017

Depletion of glutamine (Gln) has emerged as a potential therapeutic approach in the treatment of ... more Depletion of glutamine (Gln) has emerged as a potential therapeutic approach in the treatment of acute myeloid leukemia (AML), as neoplastic cells require Gln for synthesis of cellular components essential for survival. Asparaginases deplete Gln, and asparaginase derived from Erwinia chrysanthemi (Erwinaze) appears to have the greatest glutaminase activity of the available asparaginases. In this Phase I study, we sought to determine the dose of Erwinaze that safely and effectively depletes plasma Gln levels to ≤ 120 μmol/L in patients with relapsed or refractory (R/R) AML. Five patients were enrolled before the study was halted due to issues with Erwinaze manufacturing supply. All patients received Erwinaze at a dose of 25,000 IU/m2 intravenously three times weekly for 2 weeks. Median trough plasma Gln level at 48 h after initial Erwinaze administration was 27.6 μmol/L, and 80% (lower limit of 1-sided 95% CI 34%) of patients achieved at least one undetectable plasma Gln value (< ...

Annals of hematology, Jan 22, 2017

The prognostic value of peripheral blasts (PB) is not well-studied in patients with myelodysplast... more The prognostic value of peripheral blasts (PB) is not well-studied in patients with myelodysplastic syndromes (MDS). We evaluated the impact of PB on overall survival (OS) and transformation to acute myeloid leukemia (AML) in a large cohort. The MDS database at the Moffitt Cancer Center was retrospectively reviewed to identify patients with ≥ 1% PB (PB-MDS) and those without PB (BM-MDS). We also assessed the correlation between PB and gene mutations. One thousand seven hundred fifty-eight patients were identified, among whom 13% had PB near the time of diagnosis. PB-MDS patients were more likely to be younger with trilineage cytopenia, complex karyotype, higher-risk disease, transfusion dependence, and therapy-related MDS. The rate of AML transformation was 49 vs. 26% (p < 0.005) and median OS was 16.5 vs. 45.8 months (p < 0.005) in the PB-MDS and BM-MDS groups, respectively. In Cox regression analysis, the presence of PB was an independent prognostic covariate for OS, HR 1.57...

Cancer cell, Oct 10, 2016

Poly (ADP-ribose) polymerase inhibitors (PARPis) are clinically effective predominantly for BRCA-... more Poly (ADP-ribose) polymerase inhibitors (PARPis) are clinically effective predominantly for BRCA-mutant tumors. We introduce a mechanism-based strategy to enhance PARPi efficacy based on DNA damage-related binding between DNA methyltransferases (DNMTs) and PARP1. In acute myeloid leukemia (AML) and breast cancer cells, DNMT inhibitors (DNMTis) alone covalently bind DNMTs into DNA and increase PARP1 tightly bound into chromatin. Low doses of DNMTis plus PARPis, versus each drug alone, increase PARPi efficacy, increasing amplitude and retention of PARP1 directly at laser-induced DNA damage sites. This correlates with increased DNA damage, synergistic tumor cytotoxicity, blunting of self-renewal, and strong anti-tumor responses, in vivo in unfavorable AML subtypes and BRCA wild-type breast cancer cells. Our combinatorial approach introduces a strategy to enhance efficacy of PARPis in treating cancer.

Clinical lymphoma, myeloma & leukemia, Aug 1, 2016

Eltrombopag used for thrombocytopenia in myelodysplastic syndrome (MDS) patients is being explore... more Eltrombopag used for thrombocytopenia in myelodysplastic syndrome (MDS) patients is being explored in clinical trials including those with chronic myelomonocytic leukemia (CMML). We report our experience treating patients with CMML enrolled in a sequential 2-stage dose escalation study with eltrombopag in patients with MDS after hypomethylating agent failure. Patients with CMML were compared with patients with MDS in respect to response and adverse events. Among 33 patients in the study, we treated 7 patients with CMML. Hematological improvement or better (by International Working Group 2006 criteria) was observed in 6 (23%) of 26 MDS patients and 1 (14%) of 7 patients with CMML. The responding patient with CMML had bilineage response. Two patients with CMML became platelet transfusion-independent. Five (71%) patients with CMML developed leukocytosis compared with 3 (12%) patients with MDS. Four (57%) patients with CMML showed peripheral myeloblasts after treatment compared with 11 ...

American Journal of Managed Care, Mar 17, 2015