ORCID Profile
0000-0003-0143-6263
Current Organisations
Singapore General Hospital
,
National Cancer Centre Singapore
,
Duke-NUS Medical School
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Publications
Cord blood unit factors influencing transplant outcomes from the Asian multiethnic Singapore Cord Blood Bank
Publisher: Springer Science and Business Media LLC
Date: 08-06-2015
DOI: 10.1038/BMT.2015.134
Towards elimination of cervical cancer- human papillomavirus (HPV) vaccination and cervical cancer screening in Asian National Cancer Centers Alliance (ANCCA) member countries
Publisher: Elsevier BV
Date: 10-2023
Long‐term renal outcome after allogeneic hemopoietic stem cell transplant: A comprehensive analysis of risk factors in an Asian patient population
Publisher: Wiley
Date: 03-2017
DOI: 10.1111/CTR.12920
Abstract: Allogeneic hemopoietic stem cell transplantation (allo-HSCT) poses a significant challenge to renal function due to multiple drug- and complication-related renal toxicity. In this single-center series of 216 adult Asian patients with a long and complete follow-up, 41 developed chronic kidney disease (CKD) giving a cumulative incidence of 19.0% at 25 years (median follow-up duration 7.84 years, range 2.0-27.7 years), but only two of the 41 patients reached stage 4 CKD and another two required dialysis. In contrast, acute kidney injury occurred in most patients, where glomerular filtration rate (GFR) suffered a mean fall of 50 mL/min/1.73 m
Developmental Analysis of Bone Marrow Neutrophils Reveals Populations Specialized in Expansion, Trafficking, and Effector Functions
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.IMMUNI.2018.02.002
Abstract: Neutrophils are specialized innate cells that require constant replenishment from proliferative bone marrow (BM) precursors as a result of their short half-life. Although it is established that neutrophils are derived from the granulocyte-macrophage progenitor (GMP), the differentiation pathways from GMP to functional mature neutrophils are poorly defined. Using mass cytometry (CyTOF) and cell-cycle-based analysis, we identified three neutrophil subsets within the BM: a committed proliferative neutrophil precursor (preNeu) which differentiates into non-proliferating immature neutrophils and mature neutrophils. Transcriptomic profiling and functional analysis revealed that preNeu require the C/EBPε transcription factor for their generation from the GMP, and their proliferative program is substituted by a gain of migratory and effector function as they mature. preNeus expand under microbial and tumoral stress, and immature neutrophils are recruited to the periphery of tumor-bearing mice. In summary, our study identifies specialized BM granulocytic populations that ensure supply under homeostasis and stress responses.
Fanconi's Anemia in Adulthood: Chemoradiation-Induced Bone Marrow Failure and a Novel FANCA Mutation Identified by Targeted Deep Sequencing
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-07-2011
Protective role of functionalized single walled carbon nanotubes enhance ex vivo expansion of hematopoietic stem and progenitor cells in human umbilical cord blood.
Publisher: Elsevier BV
Date: 11-2013
DOI: 10.1016/J.NANO.2013.05.009
Abstract: In this study, carboxylic acid functionalized single walled carbon nanotubes (f-SWCNT-COOH) was shown to support the viability and ex vivo expansion of freeze-thawed, non-enriched hematopoietic stem and progenitor cells (HSPC) in human umbilical cord blood-mononucleated cells (UCB-MNC). Our in vitro experiments showed that f-SWCNT-COOH increased the viability of the CD45(+) cells even without cytokine stimulation. It also reduced mitochondrial superoxides and caspase activity in CD45(+) cells. f-SWCNT-COOH drastically reduced the proportions of CD45(-) cells in the non-enriched UCB-MNC. Phenotypic expression analysis and functional colony forming units (CFU) showed significant ex vivo expansion of HSPC, particularly of CD45(+)CD34(+)CD38(-) population and granulocyte-macrophage (GM) colonies, in f-SWCNT-COOH augmented cultures supplemented with basal cytokines. In vivo data suggested that f-SWCNT-COOH expanded UCB-MNC could repopulate immunodeficient mice models with minimal acute or sub-acute symptoms of graft-versus-host disease (GVHD) and f-SWCNT-COOH dependent toxicity. In this paper a novel method is presented by using single wall functionalized carbon nanotubes to enhance viability and ex vivo expansion of freeze-thawed, non-enriched hematopoietic stem and progenitor cells in human umbilical cord blood -mononucleated cells. Detailed data is presented about enhanced viability, including improved repopulation of immunodeficient mice models with minimal acute or sub-acute symptoms of graft-versus-host disease.
Towards a global system of vigilance and surveillance in unrelated donors of haematopoietic progenitor cells for transplantation
Publisher: Springer Science and Business Media LLC
Date: 29-07-2013
DOI: 10.1038/BMT.2013.104
Abstract: Safety of living donors is critical to the success of blood, tissue and organ transplantation. Structured and robust vigilance and surveillance systems exist as part of some national entities, but historically no global systems are in place to ensure conformity, harmonisation and the recognition of rare adverse events (AEs). The World Health Assembly has recently resolved to require AE/reaction (AE/R) reporting both nationally and globally. The World Marrow Donor Association (WMDA) is an international organisation promoting the safety of unrelated donors and progenitor cell products for use in haematopoietic progenitor cell (HPC) transplantation. To address this issue, we established a system for collecting, collating, analysing, distributing and reacting to serious adverse events and reactions (SAE/R) in unrelated HPC donors. The WMDA successfully instituted this reporting system with 203 SAE/R reported in 2011. The committee generated two rapid reports, reacting to specific SAE/R, resulting in practice changing policies. The system has a robust governance structure, formal feedback to the WMDA membership and transparent information flows to other agencies, specialist physicians and transplant programs and the general public.
Donor‐type fresh frozen plasma is effective in preventing hemolytic reaction in major ABO incompatible allogeneic stem cell transplant
Publisher: Wiley
Date: 22-11-2018
DOI: 10.1111/TRF.15053
Abstract: Hemolysis at the time of graft infusion is one of the immediate complications in major ABO-incompatible allogeneic hematopoietic stem cell transplants (HSCTs). We conducted a retrospective analysis to evaluate the efficacy of donor-type fresh frozen plasma (FFP) in reducing isohemagglutinin titer and preventing hemolysis, as well as its effect on delayed red cell engraftment. This is a single-center study on a series of 380 allogeneic HSCT between 2005 and 2015 of which 99 were either major (n = 74) or bidirectional (n = 25) ABO mismatched. Pre-transplant infusion of FFP, post-transplant complications and transfusion requirements were determined by retrospective review of in idual medical records. Laboratory results were also reviewed for evidence of hemolysis and pure red cell aplasia (PRCA). Clinical manifestation of hemolysis attributable to ABO mismatch was present in one recipient of major ABO-incompatible peripheral blood stem cell (PBSC) with a titer of 64. Another recipient of major ABO-incompatible PBSC with a titer of 64 showed biochemical evidence of hemolysis. Both patients recovered with supportive treatment. Hemolysis did not occur in any patients with titer of 32 or less at the time of stem cell infusion. We were unable to demonstrate the influence of any variables on the incidence of PRCA. Our experience demonstrated that donor-type FFP is safe and effective in preventing acute hemolysis in major ABO-mismatched HSCT. We have also established the titer of 64 as the threshold that may cause hemolysis and therefore efforts should be made to reduce titer to below this level.
Combinatorial Single-Cell Analyses of Granulocyte-Monocyte Progenitor Heterogeneity Reveals an Early Uni-potent Neutrophil Progenitor
Publisher: Elsevier BV
Date: 08-2020
Large-Scale Whole-Genome Sequencing of Three Diverse Asian Populations in Singapore
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.CELL.2019.09.019
Abstract: Underrepresentation of Asian genomes has hindered population and medical genetics research on Asians, leading to population disparities in precision medicine. By whole-genome sequencing of 4,810 Singapore Chinese, Malays, and Indians, we found 98.3 million SNPs and small insertions or deletions, over half of which are novel. Population structure analysis demonstrated great representation of Asian genetic ersity by three ethnicities in Singapore and revealed a Malay-related novel ancestry component. Furthermore, demographic inference suggested that Malays split from Chinese ∼24,800 years ago and experienced significant admixture with East Asians ∼1,700 years ago, coinciding with the Austronesian expansion. Additionally, we identified 20 candidate loci for natural selection, 14 of which harbored robust associations with complex traits and diseases. Finally, we show that our data can substantially improve genotype imputation in erse Asian and Oceanian populations. These results highlight the value of our data as a resource to empower human genetics discovery across broad geographic regions.
Preparing for the Next Pandemic: An Asian National Cancer Centers Alliance (ANCCA) Initiative
Publisher: EpiSmart Science Vector Ltd
Date: 09-2021
Mitochondrial superoxide reduction and cytokine secretion skewing by carbon nanotube scaffolds enhance ex vivo expansion of human cord blood hematopoietic progenitors.
Publisher: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.NANO.2015.06.005
Abstract: In this study, we report that surface functional groups of single walled carbon nanotubes (f-SWCNT) are critical for mediating survival and ex vivo expansion of hematopoietic stem and progenitor cells (HSPC) in human umbilical cord blood (UCB). In comparison to amide (-O-NH2) and polyethylene-glycol (-PEG) functionalized SWCNT, carboxylic acid (-COOH) variants gave optimal viability support which correlated with maximal reduction of lethal mitochondrial superoxides in HSPC. Cytokine array illustrated that f-SWCNT-COOH maintained higher proportion of HSPC associated cytokines and minimal level of differentiation promoting factors. Transplantation of f-SWCNT-COOH expanded grafts in sub-lethally irradiated immunodeficient mice resulted in higher engraftment of HSPC in bone marrow compared to control when they were co-transplanted with non-expanded cells from the same UCB. Expanded grafts mediated higher survival rate of mice compared to non-expanded grafts due to lower graft-versus-host-disease which is likely a consequence of proportion of immune cells in the grafts. Umbilical cord blood (UCB) is a potential source of hematopoietic stem and progenitor (HSPC) cells. One major hurdle for its clinical use is the insufficient yield of cell number. The authors in this study elegantly demonstrated the importance of various functional groups on single-walled carbon nanotubes (f-SWCNT) in enhancing ex vivo expansion of HSPC in UCB. The findings may pave a way for having UCB as a source for HSPC for clinical use in the future.
WPSS is a strong prognostic indicator for clinical outcome of allogeneic transplant for myelodysplastic syndrome in Southeast Asian patients
Publisher: Springer Science and Business Media LLC
Date: 18-12-2014
DOI: 10.1007/S00277-014-2275-X
Abstract: To better understand the predictive factors and improve clinical outcome of allogeneic transplant for patients with myelodysplastic syndrome (MDS), we retrospectively analyzed the post-transplant outcome of 60 Southeast Asian patients with MDS. Multivariate analysis showed that WHO classification-based Prognostic Scoring System (WPSS) significantly affect overall survival (OS), progression-free survival (PFS), cumulative incidence of relapse (CIR), and cumulative incidence of non-relapse mortality (CINRM). Stratified by WPSS into very low/low, intermediate, high, and very high-risk categories, 3-year OS was 100, 61, 37, and 18% (p = 0.02) PFS was 100, 55, 32, and 18% (p = 0.014) CIR was 12, 24, 38, and 59% (p = 0.024) CINRM was 0, 6, 12, and 26% (p = 0.037), respectively. WHO classification, Revised International Prognostic Scoring System (IPSS-R), IPSS-R-defined cytogenetic risk groups, donor gender, and acute and chronic graft vs host disease (GVHD) also influenced different aspects of transplant outcome. We found that WPSS is a powerful predictor of post-transplant outcome. WPSS provides an important model not only for prognostication but also for exploration of further post-transplant measures such as immunological maneuvers or novel therapy to improve the poor outcome of high-risk patients.
Early relapse post autologous transplant is a stronger predictor of survival compared with pretreatment patient factors in the novel agent era: analysis of the Singapore Multiple Myeloma Working Group
Publisher: Springer Science and Business Media LLC
Date: 14-03-2016
DOI: 10.1038/BMT.2016.43
Abstract: The clinical outcome of multiple myeloma is heterogeneous. Both the depth of response to induction and transplant as well as early relapse within a year are correlated with survival, but it is unclear which factor is most relevant in Southeast Asian patients with multiple myeloma. We retrospectively analyzed outcomes of 215 patients who were treated with upfront autologous transplant in Singapore between 2000 and 2014. In patients who received novel agent (NA)-based induction, achieving only partial response (PR) post-induction was associated with poorer OS (HR 1.95, P=0.047) and PFS (HR 2.9, P<0.001), while achieving only PR post-transplant was strongly correlated with both OS (HR 3.3, P=0.001) and PFS (HR 7.6, P<0.001), compared with patients who achieved very good partial response (VGPR) or better. Early relapse was detected in 18% of all patients, although nearly half had initially achieved VGPR or better post-transplant. Early relapse after NA-based induction led to significantly shorter OS (median 22 months vs not reached, P<0.001), and was strongly associated with OS (HR 13.7, P<0.001). The impact of suboptimal post-transplant response and early relapse on survival may be more important than pretransplant factors, such as International Staging System or cytogenetics, and should be considered in risk stratification systems to rationalize therapy.
What We Learned From Plasma BK-Virus Monitoring in Allogeneic Hematopoietic Transplant Recipients
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2016
BK-virus prophylaxis: still no answer
Publisher: Springer Science and Business Media LLC
Date: 06-05-2013
DOI: 10.1038/BMT.2013.62
An exploration of the applicability of the refined disease risk index and its integration with other independent risk factors for individualized prognostication
Publisher: Springer Science and Business Media LLC
Date: 31-10-2016
DOI: 10.1038/BMT.2016.286
Abstract: The refined disease risk index (DRI) is a powerful prognostic model based solely on the disease type and stage for predicting survival outcomes of various hematological malignancies after allogeneic transplant. Here, we analyzed our series of 690 patients transplanted over the past 15 years, and showed that besides overall survival (OS), the refined DRI is also able to segregate event-free survival and relapse mortality in our cohort of largely Southeast Asian patients with a long and complete follow-up. Stratification by refined DRI remains statistically significant even when broken down by specific diseases each with a smaller number of patients, as well as for a small subset of patients younger than 18 years old, providing a robust model for prognostication. Multivariable analysis shows that refined DRI, age, year of transplant and donor type are independent risk factors for OS. We further demonstrated here that prognostication for a given patient with a specific disease can be made more discriminating by integrating independent risk factors such as age and donor type with the refined DRI. The future development of prognostic system incorporating the refined DRI with patient- and transplant-related risk factors will provide a more precise estimate of transplant outcome.
Use of Valacyclovir for the treatment of cytomegalovirus antigenemia after hematopoietic stem cell transplantation
Publisher: Springer Science and Business Media LLC
Date: 19-06-2015
Recurrent trichosporonosis with central nervous system involvement in an allogeneic hematopoietic stem cell transplant recipient
Publisher: Wiley
Date: 07-09-2016
DOI: 10.1111/TID.12577
Abstract: Trichosporon is an ubiquitous yeast that has emerged as an opportunistic pathogen in the immunocompromised host. We describe a case of invasive trichosporonosis in an allogeneic hematopoietic stem cell transplant (allo-HSCT) recipient while on caspofungin antifungal prophylaxis. She developed disseminated trichosporonosis in the pre-engraftment period and was successfully treated with voriconazole. She later developed 2 further episodes of invasive trichosporonosis involving the central nervous system. This case highlights the challenges of managing trichosporonosis in allo-HSCT recipients and suggests the need for lifelong therapy in some patients.
Mobilization kinetics of peripheral blood stem cells with rescue plerixafor – real-world experience from a single center
Publisher: Informa UK Limited
Date: 24-02-2020
Pre-transplant achievement of negativity in minimal residual disease and French–American–British L1 morphology predict superior outcome after allogeneic transplant for Philadelphia chromosome positive
Publisher: Informa UK Limited
Date: 24-10-2014
DOI: 10.3109/10428194.2014.956318
Abstract: To better understand predictive factors and improve the clinical outcome of allogeneic transplant for patients with Philadelphia positive acute lymphoblastic leukemia, we analyzed 67 Southeast Asian patients transplanted in our institutions. Multivariate analysis showed that disease status before transplant, year of transplant and, interestingly, French-American-British (FAB) subtype had a significant impact on overall survival (OS) and non-relapse mortality. Patients who were minimal residual disease (MRD) negative at transplant had a 3-year OS of 73% compared to those who were MRD positive (45%) and refractory (0%). The 3-year cumulative incidence of relapse was 18% and 36% for the MRD negative and positive groups, respectively. FAB L1 subtype had a significantly superior 3-year OS of 63% vs. 29% for L2 subtype. Pre-transplant use of a tyrosine kinase inhibitor significantly improved outcomes in univariate but not multivariate analysis, as it served to induce more patients into MRD negativity, which was the factor that directly improved transplant outcome.
Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
Publisher: Wiley
Date: 10-2019
Abstract: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring ex les of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer‐reviewed by leading experts in the field, making this an essential research companion.
Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)
Publisher: Wiley
Date: 12-2021
Abstract: The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical s les with ex les of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer‐reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state‐of‐the‐art handbook for basic and clinical researchers.
Respiratory virus infection after allogeneic hematopoietic stem cell transplant in a tropical center: Predictive value of the immunodeficiency scoring index
Publisher: Wiley
Date: 27-04-2017
DOI: 10.1111/TID.12693
Related Organisations
Related Funding Activities
No related grants have been discovered for William Ying Khee Hwang.