Alan K S Chiang

The University of Hong Kong | HKU · Department of Paediatrics and Adolescent Medicine

Epstein–Barr virus (EBV) is a prevalent human gamma-herpesvirus that infects the majority of the adult population worldwide and is associated with several lymphoid and epithelial malignancies. EBV displays a biphasic life cycle, namely, latent and lytic replication cycles, expressing a diversity of viral proteins. Among the EBV proteins being expre...

Background: Survival of children and adolescents with high-risk, mature B-cell non-Hodgkin lymphoma is improved by the addition of rituximab to chemotherapy. The effect of rituximab on immune reconstitution after therapy has not been well described. Herein, we evaluate the immune effects of the addition of rituximab to intensive chemotherapy, a pr...

Background: Avascular necrosis (AVN) of bone is a debilitating complication of pediatric patients with acute lymphoblastic leukemia (ALL). While it is extensively studied and reported in Western population, studies focused on Orientals are limited. This study aims to evaluate the incidence, risk factors, and clinical outcomes of AVN among Chinese...

This brief report aims to evaluate the treatment outcome of transarterial embolization in ruptured hepatoblastoma complicated with acute intra‐abdominal hemorrhage. Three children (mean age 6 years) with high‐risk hepatoblastoma presented with rupture and acute intra‐abdominal hemorrhage. In addition to aggressive fluid resuscitation and blood prod...

Despite the expanding portfolio of targeted therapies for adults with acute myeloid leukemia (AML), direct implementation in children is challenging due to inherent differences in underlying genetics. Here we established the pharmacologic profile of pediatric AML by screening myeloblast sensitivity to approved and investigational agents, revealing...

B-cell lymphoblastic lymphoma (BCP-LBL) and B-cell acute lymphoblastic leukemia (BCP-ALL) are the malignant counterparts of immature B-cells. BCP-ALL is the most common hematological malignancy in childhood, while BCP-LBL accounts for only 1% of all hematological malignancies in children. Therefore, BCP-ALL has been well studied and treatment proto...

Background Transplant-associated thrombotic microangiopathy (TA-TMA) is an under-recognized yet potentially devastating complication of hematopoietic stem cell transplantation (HSCT) which had increased awareness in recent years. This report summarizes the demographics and outcomes of pediatric TA-TMA in Hong Kong. Methods All patients aged below...

Introduction: Compared with young children who have acute lymphoblastic leukaemia (ALL), adolescents with ALL have unfavourable disease profiles and worse survival. However, limited data are available regarding the characteristics and outcomes of adolescents with ALL who underwent treatment in clinical trials. The aim of this study was to investig...

Jejunal feeding is increasingly utilized in the pediatric population to reduce gastroesophageal reflux or aspiration pneumonia. We describe a pediatric patient who developed persistent neutropenia and anemia secondary to copper deficiency after more than one year of exclusive jejunal feeding. Bone marrow aspiration and trephine biopsy showed vacuol...

Background Hematopoietic stem cell transplantation, despite being a curative treatment for various pediatric disorders, is associated with significant acute and chronic complications. Methods This retrospective review of 196 hematopoietic stem cell transplantation episodes (144 allogeneic, 52 autologous) performed in a tertiary pediatric unit focu...

Asparaginase is an important drug to treat childhood haematological malignancies. Data on the association between human leukocyte antigens (HLA) and asparaginase hypersensitivity among Chinese are lacking. We conducted a retrospective study to identify HLA alleles associated with asparaginase hypersensitivity among Chinese children with acute lymph...

Non-tuberculous mycobacterial (NTM) infection is uncommon yet clinically significant as it could cause severe morbidity and mortality. This study reviewed all paediatric patients under 20 years of age diagnosed to have NTM infection in Queen Mary Hospital during 1 January 1999 to 30 June 2018. Total 7 patients were identified with median age of dia...

PURPOSE A dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone plus rituximab (DA-EPOCH-R) regimen has been shown to deliver excellent survival for adults with primary mediastinal large B-cell lymphoma (PMLBL) without the use of radiotherapy. No international prospective evaluation of this regimen has previousl...

Purpose: Children with mediastinal masses often present with insidious symptoms to nonspecialist centers and require interhospital transport to oncology centers for definitive care. We evaluated clinical characteristics and patient outcomes and proposed a management protocol. Materials and methods: This is a retrospective review of all children...

p>The reactivation of lytic cycle of Epstein-Barr Virus (EBV) is an important component of the emerging lytic induction therapy to specifically target the virus in EBV-associated malignancies. The potency of the lytic induction is central to the effectiveness of the lytic induction therapy. It is hampered by cancer cells that are refractory to lyti...

Germline adenomatous polyposis coli (APC) gene mutation is a cancer-predisposing condition commonly presenting as familial adenomatous polyposis. We describe a patient first diagnosed at the age of 3 years with metastatic hepatoblastoma. With a positive family history, germline testing confirmed maternally inherited APC mutation (p.Thr899Ansfs*13)....

Despite poor survival, controversies remain in the treatment for refractory or relapsed pediatric non-Hodgkin lymphoma (r/r NHL). The current project aimed to collect international experience on the re-induction treatment of r/r NHL, hematopoietic stem cell transplantation (HSCT), risk factors associated with outcome, and to suggest treatment recom...

Primary central nervous system (CNS) post‐transplant lymphoproliferative disorder (PTLD) in childhood is rare. Twenty‐five patients were retrieved from nine European Intergroup for Childhood Non‐Hodgkin’s Lymphoma and/or international Berlin–Frankfurt–Münster Study Group members. Types of allografts included kidney (n = 11), liver (n = 4), heart (n...

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...

Data on the spectrum of second malignant neoplasms (SMNs) after primary childhood non-Hodgkin’s lymphoma (NHL) are scarce. One-hundred-and-eighty-nine NHL patients diagnosed in a 30 years period of 1980–2010 developing an SMN were retrieved from 19 members of the European Intergroup for Childhood NHL and/or the international Berlin-Frankfurt-Münste...

the PDF can be download freely on pubmed. https://pubmed.ncbi.nlm.nih.gov/33634751/

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...

[This corrects the article DOI: 10.1371/journal.ppat.1008477.].

Allogeneic hematopoietic stem cell transplantation is curative for transfusion-dependent thalassemia, but mixed chimerism (MC) may herald graft rejection. We report a child who failed bone marrow transplant (BMT) from matched unrelated donor (MUD) successfully salvaged with haploidentical peripheral blood stem cell transplant (PBSCT), but had MC in...

Epstein-Barr virus (EBV) is strongly associated with lymphoproliferative diseases (LPDs), in particular B cell, in both immunocompetent and immunocompromised hosts. The virus is able to manipulate host cell machineries such as the ubiquitin-proteasome system and regulators of Bcl-2 family to enable the persistence of the virus and the survival of t...

Background: Hepatocellular carcinoma (HCC) is a rare hepatic malignancy in children. HBV infection is a key predisposing factor in endemic regions but its impact on outcome has not been studied. We aim to evaluate the prognostic implication of HBV seropositivity and role of cancer surveillance in children with HCC from East Asian populations with n...

Epstein–Barr virus (EBV) lytic induction therapy is an emerging virus-targeted therapeutic approach that exploits the presence of EBV in tumor cells to confer specific killing effects against EBV-associated malignancies. Efforts have been made in the past years to uncover the mechanisms of EBV latent-lytic switch and discover different classes of c...

HIV and EBV are human pathogens that cause a considerable burden to worldwide health. In combination, these viruses are linked to AIDS-associated lymphomas. We found that EBV, which transforms B cells, renders them susceptible to HIV-1 infection in a CXCR4 and CD4-dependent manner in vitro and that CXCR4-tropic HIV-1 integrates into the genome of t...

Background Rituximab added to chemotherapy prolongs survival among adults with B-cell cancer. Data on its efficacy and safety in children with high-grade, mature B-cell non-Hodgkin’s lymphoma are limited. Methods We conducted an open-label, international, randomized, phase 3 trial involving patients younger than 18 years of age with high-risk, mat...

Post-transplant lymphoproliferative disorder (PTLD) is a rare but potentially life-threatening complication, frequently associated with Epstein-Barr virus (EBV), which develops after solid organ or stem cell transplantation. Immunosuppression received by transplant recipients has a significant impact on the development of PTLD by suppressing the fu...

Post-transplant lymphoproliferative disorder (PTLD) is a potentially fatal complication after organ transplantation frequently associated with the Epstein-Barr virus (EBV). Immunosuppressive treatment is thought to allow the expansion of EBV-infected B cells, which often express all eight oncogenic EBV latent proteins. Here, we assessed whether HLA...

Key Points Children with PCNSL and no immunodeficiency have a good outcome when treated by a histological subtype–driven and radiation-free protocol. New treatment guidelines are needed for PCNSL in children and adolescents with an underlying immunodeficiency.

Significance EBNA1 is the only Epstein–Barr virus (EBV) latent protein responsible for viral genome maintenance and is expressed in all EBV-infected cells. Zn ²⁺ is essential for oligomerization of the functional EBNA1. We constructed an EBNA1 binding peptide with a Zn ²⁺ chelator to create an EBNA1-specific inhibitor (ZRL 5 P 4 ). ZRL 5 P 4 by its...

Autophagy, a conserved cellular mechanism, is manipulated by a number of viruses for different purposes. We previously demonstrated that an iron-chelator-like small compound, C7, reactivates Epstein-Barr virus (EBV) lytic cycle by activating the ERK1/2-autophagy axis in epithelial cancers. Here, we aim to identify the specific stage of autophagy re...

Blastic plasmacytoid dendritic cell neoplasm is an uncommon aggressive haemato-lymphoid neoplasm derived from type 2 dendritic cells which occur mainly in adults and elderly. It usually manifests as cutaneous lesions on face, scalp, trunk or limbs. In this report, we describe a 6-year old girl with unusual presentation of septic shock and perianal...

[This corrects the article DOI: 10.18632/oncotarget.14540.].

Pharmaceutical reactivation of lytic cycle of Epstein-Barr virus (EBV) represents a potential therapeutic strategy against EBV-associated epithelial malignancies e.g. gastric carcinoma (GC) and nasopharyngeal carcinoma (NPC). A novel lytic inducing compound, C7, which exhibits structural similarity to Dp44mT, a known chelator of intracellular iron,...

Pharmaceutical reactivation of lytic cycle of Epstein-Barr virus (EBV) represents a potential therapeutic strategy against EBV-associated epithelial malignancies e.g. gastric carcinoma (GC) and nasopharyngeal carcinoma (NPC). A novel lytic inducing compound, C7, which exhibits structural similarity to Dp44mT, a known chelator of intracellular iron,...

We report the first case of microabscesses detected by polymerase chain reaction (PCR) amplification of nucleic acid from ultrasound-guided aspirated fluid in a three-year old boy with acute lymphoblastic leukemia and febrile neutropenia during induction chemotherapy. Fever persisted despite effective antifungal treatment. The addition of corticost...

Epstein-Barr virus (EBV) is strongly associated with a spectrum of EBV-associated lymphoproliferative diseases (EBV-LPDs) ranging from post-transplant lymphoproliferative disorder, B cell lymphomas (e.g., endemic Burkitt lymphoma, Hodgkin lymphoma, and diffuse large B cell lymphoma) to NK or T cell lymphoma (e.g., nasal NK/T-cell lymphoma). The vir...

Nasopharyngeal carcinoma (NPC) is an Epstein–Barr-associated malignancy. Both the host and viral factors are known to contribute to the oncogenic development of NPC. NPC has a wide mutational diversity and many signaling pathways are known to be activated in the tumor cells. However, molecularly targeted therapeutic agents licensed for the treatmen...

Pharmaceutical reactivation of lytic cycle of Epstein–Barr virus (EBV) represents a potential therapeutic strategy against EBV-associated epithelial malignancies, e.g., gastric carcinoma (GC) and nasopharyngeal carcinoma (NPC). A novel lytic-inducing compound, C7, which exhibits structural similarity to Di-2-Pyridyl Ketone 4, 4-Dimethyl-3-Thiosemic...

Whether certain variants of Epstein‐Barr virus (EBV) are linked to the pathogenesis of nasopharyngeal carcinoma (NPC), which shows a marked geographic restriction, remains an unresolved issue. We performed a case‐control study comparing genomic sequences of EBV isolated from saliva samples of 142 population carriers with those from primary tumour b...

4-year old girl with acute myeloid leukaemia (AML) t(8,21) CNS-positive disease developed prolonged neutropenic fever without obvious focus despite broad spectrum anti-bacterials and anti-fungals, later found to have right lower limb pain. She was confirmed to have right calcaneal osteomyelitis due to Mycobacterium abscessus with subcutaneous absce...

The survival rates of childhood cancers have increased significantly in recent years, and the long-term complications of childhood cancers have become an important issue. Although communication and hearing complications have been documented in survivors, they have not been widely investigated across different types of cancer. Therefore, we conducte...

The lack of representative nasopharyngeal carcinoma (NPC) models has seriously hampered research on EBV carcinogenesis and preclinical studies in NPC. Here we report the successful growth of five NPC patient-derived xenografts (PDXs) from fifty-eight attempts of transplantation of NPC specimens into NOD/SCID mice. The take rates for primary and rec...

1 Background and aim We reviewed the results and pattern of failure of the consensus HB/HCC 1996 treatment protocol for pediatric hepatoblastoma (HB) in Hong Kong. The role of SIOPEL and Children's Hepatic tumors International Collaboration (CHIC) risk stratification was evaluated. 2 Methods Patients enrolled on the protocol from 1996 to 2014 were...

BACKGROUND An 8-year old girl initially presented with petechiae for 6 months and hepatomegaly of 2 centimeters. Investigations showed platelet count of 25x109/L, haemoglobin level of 11g/dL and serial absolute neutrophil counts (ANC) around 0.7 to 1.2 x109/L. Bone marrow aspiration (BMA) and trephine showed active trilineage haematopoiesis. Intrav...

1 Objective The aim of this study was to review clinical outcomes and prognosis of paediatric patients with acute lymphoblastic leukaemia (ALL) with TCF3‐PBX1 rearrangement. 2 Patients All children in Hong Kong diagnosed with ALL with TCF3‐PBX1 rearrangement over the past two decades were included. 3 Methods Six hundred and twenty‐four newly diag...

Relapsed/refractory NB carries a bleak outcome, warranting novel treatment options. HaploHSCT induces a graft‐versus‐NB effect via natural killer cell alloreactivity. Review of patients with relapsed/refractory NB who underwent haploHSCT with ex vivo T‐cell depletion in our unit from 2013 through 2018. Ten patients were identified (male=5; median a...

Combination of suberoylanilide hydroxamic acid (SAHA) and bortezomib (SAHA/ bortezomib) was shown to synergistically induce killing of lymphoblastoid cell lines (LCL) and Burkitt lymphoma (BL) of type III or Wp-restricted latency, both of which express EBNA3A, -3B and -3C proteins. We hypothesize that SAHA/bortezomib can counteract the survival fun...

Long term carriers were shown to generate robust polyfunctional T cell (PFC) responses against lytic and latent antigens of Epstein-Barr virus (EBV). However, the time of emergence of PFC responses against EBV antigens, pattern of immunodominance and difference between CD4+ and CD8+ T cell responses during various stages of EBV infection are not cl...

Epstein-Barr virus (EBV) is closely associated with several lymphomas (endemic Burkitt lymphoma, Hodgkin lymphoma and nasal NK/T-cell lymphoma) and epithelial cancers (nasopharyngeal carcinoma and gastric carcinoma). To maintain its persistence in the host cells, the virus manipulates the ubiquitin-proteasome system to regulate viral lytic reactiva...

Currently, out of the 82 US FDA-approved targeted therapies for adult cancer treatments, only three are approved for use in children irrespective of their genomic status. Apart from leukemia, only a handful of genomic-based trials involving children with solid tumors are ongoing. Emerging genomic data for pediatric solid tumors may facilitate the d...

A total of 16 cases of congenital fibrosarcoma have been reported from 1975 to March 2015. Five of the 16 had abnormal fusion between erythroblast transformation specific translocation variant 6 and neurotrophin recptor gene neurotrophic tyrosine kinase, receptor, type 3 (ETV6-NTRK3); in another five out of 16 this was absent, and six were not test...