Background and objectives: Donor helper T-lymphocytes may be involved in graft-versus-host diseas... more Background and objectives: Donor helper T-lymphocytes may be involved in graft-versus-host disease (GVHD) and a graft-versus-leukemia effect after bone marrow transplantation (BMT). We assayed donor helper T-lymphocyte precursor frequencies (HTLP(f)) to see whether they could predict the severity of GVHD and disease relapse after transplantation, thereby facilitating donor selection, pre-transplant counselling and modification of GVHD prophylaxis after BMT. Design and methods: Thirty-six consecutive adult BMT recipients and their HLA-identical sibling donors were recruited. HTLP((f)) was measured as a function of interleukin-2 secretion by alloreactive donor T-cells using a limiting dilution assay. Patients were followed prospectively to assess the severity of GVHD and the status of the primary disease after BMT. Results: Eight donors had HTLP((f)) less than or equal to 10(-6); no recipients of these grafts developed severe GVHD after transplantation. Twenty-eight donors had HTLP(f) greater than 10(-6) and 18 recipients of these grafts developed severe GVHD (> or = grade 2) (chi(2) test, p<0.01). Seven donors had HTLP(f) greater than 10(-5) and no recipient had disease relapse. Twenty-nine donors had HTLP(f) less than or equal to 10(-5), 11 recipients of these grafts developed disease relapse (chi(2) test, p=0.08). Interpretation and conclusions: BMT recipients from HLA-identical sibling donors with low (<10(-6)) and high (>10(-5)) HTLP(f) may have a low risk of acute GVHD and disease relapse after transplantation.
We report on a case of diffuse alveolar haemorrhage in a Chinese woman due to methimazole-induced... more We report on a case of diffuse alveolar haemorrhage in a Chinese woman due to methimazole-induced antineutrophil cytoplasmic antibodies. A literature search for anti-thyroid drugs associated with antineutrophil cytoplasmic antibody-induced diffuse alveolar haemorrhages is reviewed. Diffuse alveolar haemorrhage is a rare complication of thiourea agents and the treatment often requires corticosteroids or other immunosuppressants, together with withdrawal of the causative agent.
HLA genes are the most polymorphic in the human genome. High resolution HLA typing from 13,870 bo... more HLA genes are the most polymorphic in the human genome. High resolution HLA typing from 13,870 bone marrow donors in Hong Kong was obtained using Next‐generation sequencing (NGS) technology. Among the 67 novel alleles identified, official HLA allele names of 50 novel class I alleles (HLA‐A, ‐B, ‐C) and 8 novel class II alleles (HLA‐DRB1, ‐DQB1) were assigned by the World Health Organization (WHO) Nomenclature Committee for Factors of the HLA System.
Omicron generally causes milder disease than previous strains of severe acute respiratory syndrom... more Omicron generally causes milder disease than previous strains of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), especially in fully vaccinated individuals. However, incompletely vaccinated children may develop Omicron‐related complications such as those affecting the central nervous system. To characterize the spectrum of clinical manifestations of neuro‐COVID and to identify potential biomarkers associated with clinical outcomes, we recruited 15 children hospitalized for Omicron‐related neurological manifestations in three hospitals in Hong Kong (9 boys and 6 girls aged 1–13 years). All were unvaccinated or incompletely vaccinated. Fourteen (93.3%) were admitted for convulsion, including benign febrile seizure (n = 7), complex febrile seizure (n = 2), seizure with fever (n = 3), and recurrent breakthrough seizure (n = 2), and the remaining nonconvulsive patient developed encephalopathic state with impaired consciousness. None of the seven children with benign febrile...
Human leukocyte antigen (HLA)-B*58:01 allele is a significant risk factor for allopurinol-induced... more Human leukocyte antigen (HLA)-B*58:01 allele is a significant risk factor for allopurinol-induced severe cutaneous adverse reactions (SCARs) which is potentially fatal. In some studies, chronic kidney disease (CKD) was also implicated to compound the risk of SCARs. We aim to investigate if pre-treatment HLA-B*58:01 screening can prevent allopurinol-induced SCARs in Chinese patients with CKD and its cost-effectiveness. We prospectively recruited Chinese CKD patients who required allopurinol during 2011–2015 and performed pre-treatment HLA testing (HLA screening group). Patients tested positive for HLA-B*58:01 were refrained from allopurinol while those tested negative were prescribed allopurinol. The incidence of SCARs in the HLA screening group was compared with the historical control in previous 5 years and the cost-effectiveness of HLA testing was analyzed. In the historical control (2006–2010), 3605 patients on allopurinol were screened, 22 out of 1027 (2.14%) CKD Chinese patients newly started on allopurinol developed SCARs, including 6 SJS/TEN. In the HLA screening group, 28 out of 192 patients (14.6%) tested HLA-B*58:01 positive were advised to avoid allopurinol; 156 out of 164 HLA-B*58:01-negative patients received allopurinol and none developed SCARs. The incidence rate of SCARs was significantly lower in the HLA screening group compared with controls (0% vs 2.14% respectively, p = 0.037*). The targeted HLA screening approach was associated with lower healthcare costs compared with no HLA screening (US$ 92,430 vs US$ 281,226). Pre-treatment HLA-B*58:01 screening is cost-effective to target on patients with CKD in Chinese to prevent allopurinol-induced SCARs.
BackgroundHLA‐B*15:11 is associated with carbamazepine (CBZ)‐induced severe cutaneous adverse dru... more BackgroundHLA‐B*15:11 is associated with carbamazepine (CBZ)‐induced severe cutaneous adverse drug reactions (SCARs) in Japanese and some Asian populations, but such data remains relatively limited in Chinese. Routine HLA‐B*15:02 screening is mandatory before CBZ commencement, however, SCARs related to CBZ were still observed in non‐HLA*B‐15:02 carriers.ObjectiveWe aimed to find out the prevalence of HLA‐B*15:11 in Chinese patients and its associations with CBZ‐induced SCARs.MethodWe screened 8,328 blood samples collected for HLA allele typing before CBZ commencement during the period of January 2014 to December 2019. In HLA‐B*15:02 negative Chinese patients, HLA‐B*15:11 status were further screened, and the incidence of SCARs in the CBZ group was compared with the control group without CBZ use.ResultIn this cohort, 1416 out of 8328 patients (17%) tested HLA‐B*15:02 positive and were advised to avoid CBZ, while 80 (0.96%) were found to be HLA‐B*15:11 positive. In 6911 (83%) patients...
Background: Evidence about the impact of marital status before hematopoietic cell transplantation... more Background: Evidence about the impact of marital status before hematopoietic cell transplantation (hct) on outcomes after hct is conflicting. Methods: We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent hct between January 2008 and December 2015. Marital status before hct was declared as one of: married or living with a partner, single (never married), separated or divorced, and widowed. We performed a multivariable analysis to determine the association of marital status with outcomes after hct. Results: We identified 10,226 allogeneic and 5714 autologous hct cases with, respectively, a median follow-up of 37 months (range: 1–102 months) and 40 months (range: 1–106 months). No association between marital status and overall survival was observed in either the allogeneic (p = 0.58) or autologous (p = 0.17) setting. However, marital status was associated with grades 2–4 acute graft-versus-host ...
The primary goal of the HLA‐DPA1 ~ promoter ~ HLA‐DPB1 haplotype component of the 18th IHIWS was ... more The primary goal of the HLA‐DPA1 ~ promoter ~ HLA‐DPB1 haplotype component of the 18th IHIWS was to characterise the extended haplotypes within the HLA‐DP region and survey the extent of genetic diversity in this region across human populations. In this report, we analysed single‐nucleotide polymorphisms (SNPs) in 255 subjects from 6 different cohorts. The results from the HLA‐DP haplotype component have validated findings from the initial pilot study. SNPs in this region were inherited in strong linkage, particularly HLA‐DPA1, SNP‐linked promoter haplotypes and motifs in exon 2 of HLA‐DPB1. We reported 17 SNP‐linked haplotypes in the promoter region. Together with HLA‐DPA1 and HLA‐DPB1 alleles, they formed 74 distinct extended HLA‐DP haplotypes in 438 sequences. We also observed the presence of region‐specific alleles and promoter haplotypes. Our approach involved phasing extended SNPs including promoter SNPs, HLA‐DPA1 and HLA‐DPB1 alleles, in a 22 kb region, GRCh38/hg38 (chr6:33,0...
Background and Objectives. Donor helper T-lymphocytes may be involved in graft-versus-host diseas... more Background and Objectives. Donor helper T-lymphocytes may be involved in graft-versus-host disease (GVHD) and a graft-versus-leukemia effect after bone marrow transplantation (BMT). We assayed donor helper T-lymphocyte precursor frequencies (HTLPf) to see whether they could predict the severity of GVHD and disease relapse after transplantation, thereby facilitating donor selection, pre-transplant counselling and modification of GVHD prophylaxis after BMT.
Background and objectives: Donor helper T-lymphocytes may be involved in graft-versus-host diseas... more Background and objectives: Donor helper T-lymphocytes may be involved in graft-versus-host disease (GVHD) and a graft-versus-leukemia effect after bone marrow transplantation (BMT). We assayed donor helper T-lymphocyte precursor frequencies (HTLP(f)) to see whether they could predict the severity of GVHD and disease relapse after transplantation, thereby facilitating donor selection, pre-transplant counselling and modification of GVHD prophylaxis after BMT. Design and methods: Thirty-six consecutive adult BMT recipients and their HLA-identical sibling donors were recruited. HTLP((f)) was measured as a function of interleukin-2 secretion by alloreactive donor T-cells using a limiting dilution assay. Patients were followed prospectively to assess the severity of GVHD and the status of the primary disease after BMT. Results: Eight donors had HTLP((f)) less than or equal to 10(-6); no recipients of these grafts developed severe GVHD after transplantation. Twenty-eight donors had HTLP(f) greater than 10(-6) and 18 recipients of these grafts developed severe GVHD (> or = grade 2) (chi(2) test, p<0.01). Seven donors had HTLP(f) greater than 10(-5) and no recipient had disease relapse. Twenty-nine donors had HTLP(f) less than or equal to 10(-5), 11 recipients of these grafts developed disease relapse (chi(2) test, p=0.08). Interpretation and conclusions: BMT recipients from HLA-identical sibling donors with low (<10(-6)) and high (>10(-5)) HTLP(f) may have a low risk of acute GVHD and disease relapse after transplantation.
We report on a case of diffuse alveolar haemorrhage in a Chinese woman due to methimazole-induced... more We report on a case of diffuse alveolar haemorrhage in a Chinese woman due to methimazole-induced antineutrophil cytoplasmic antibodies. A literature search for anti-thyroid drugs associated with antineutrophil cytoplasmic antibody-induced diffuse alveolar haemorrhages is reviewed. Diffuse alveolar haemorrhage is a rare complication of thiourea agents and the treatment often requires corticosteroids or other immunosuppressants, together with withdrawal of the causative agent.
HLA genes are the most polymorphic in the human genome. High resolution HLA typing from 13,870 bo... more HLA genes are the most polymorphic in the human genome. High resolution HLA typing from 13,870 bone marrow donors in Hong Kong was obtained using Next‐generation sequencing (NGS) technology. Among the 67 novel alleles identified, official HLA allele names of 50 novel class I alleles (HLA‐A, ‐B, ‐C) and 8 novel class II alleles (HLA‐DRB1, ‐DQB1) were assigned by the World Health Organization (WHO) Nomenclature Committee for Factors of the HLA System.
Omicron generally causes milder disease than previous strains of severe acute respiratory syndrom... more Omicron generally causes milder disease than previous strains of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), especially in fully vaccinated individuals. However, incompletely vaccinated children may develop Omicron‐related complications such as those affecting the central nervous system. To characterize the spectrum of clinical manifestations of neuro‐COVID and to identify potential biomarkers associated with clinical outcomes, we recruited 15 children hospitalized for Omicron‐related neurological manifestations in three hospitals in Hong Kong (9 boys and 6 girls aged 1–13 years). All were unvaccinated or incompletely vaccinated. Fourteen (93.3%) were admitted for convulsion, including benign febrile seizure (n = 7), complex febrile seizure (n = 2), seizure with fever (n = 3), and recurrent breakthrough seizure (n = 2), and the remaining nonconvulsive patient developed encephalopathic state with impaired consciousness. None of the seven children with benign febrile...
Human leukocyte antigen (HLA)-B*58:01 allele is a significant risk factor for allopurinol-induced... more Human leukocyte antigen (HLA)-B*58:01 allele is a significant risk factor for allopurinol-induced severe cutaneous adverse reactions (SCARs) which is potentially fatal. In some studies, chronic kidney disease (CKD) was also implicated to compound the risk of SCARs. We aim to investigate if pre-treatment HLA-B*58:01 screening can prevent allopurinol-induced SCARs in Chinese patients with CKD and its cost-effectiveness. We prospectively recruited Chinese CKD patients who required allopurinol during 2011–2015 and performed pre-treatment HLA testing (HLA screening group). Patients tested positive for HLA-B*58:01 were refrained from allopurinol while those tested negative were prescribed allopurinol. The incidence of SCARs in the HLA screening group was compared with the historical control in previous 5 years and the cost-effectiveness of HLA testing was analyzed. In the historical control (2006–2010), 3605 patients on allopurinol were screened, 22 out of 1027 (2.14%) CKD Chinese patients newly started on allopurinol developed SCARs, including 6 SJS/TEN. In the HLA screening group, 28 out of 192 patients (14.6%) tested HLA-B*58:01 positive were advised to avoid allopurinol; 156 out of 164 HLA-B*58:01-negative patients received allopurinol and none developed SCARs. The incidence rate of SCARs was significantly lower in the HLA screening group compared with controls (0% vs 2.14% respectively, p = 0.037*). The targeted HLA screening approach was associated with lower healthcare costs compared with no HLA screening (US$ 92,430 vs US$ 281,226). Pre-treatment HLA-B*58:01 screening is cost-effective to target on patients with CKD in Chinese to prevent allopurinol-induced SCARs.
BackgroundHLA‐B*15:11 is associated with carbamazepine (CBZ)‐induced severe cutaneous adverse dru... more BackgroundHLA‐B*15:11 is associated with carbamazepine (CBZ)‐induced severe cutaneous adverse drug reactions (SCARs) in Japanese and some Asian populations, but such data remains relatively limited in Chinese. Routine HLA‐B*15:02 screening is mandatory before CBZ commencement, however, SCARs related to CBZ were still observed in non‐HLA*B‐15:02 carriers.ObjectiveWe aimed to find out the prevalence of HLA‐B*15:11 in Chinese patients and its associations with CBZ‐induced SCARs.MethodWe screened 8,328 blood samples collected for HLA allele typing before CBZ commencement during the period of January 2014 to December 2019. In HLA‐B*15:02 negative Chinese patients, HLA‐B*15:11 status were further screened, and the incidence of SCARs in the CBZ group was compared with the control group without CBZ use.ResultIn this cohort, 1416 out of 8328 patients (17%) tested HLA‐B*15:02 positive and were advised to avoid CBZ, while 80 (0.96%) were found to be HLA‐B*15:11 positive. In 6911 (83%) patients...
Background: Evidence about the impact of marital status before hematopoietic cell transplantation... more Background: Evidence about the impact of marital status before hematopoietic cell transplantation (hct) on outcomes after hct is conflicting. Methods: We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent hct between January 2008 and December 2015. Marital status before hct was declared as one of: married or living with a partner, single (never married), separated or divorced, and widowed. We performed a multivariable analysis to determine the association of marital status with outcomes after hct. Results: We identified 10,226 allogeneic and 5714 autologous hct cases with, respectively, a median follow-up of 37 months (range: 1–102 months) and 40 months (range: 1–106 months). No association between marital status and overall survival was observed in either the allogeneic (p = 0.58) or autologous (p = 0.17) setting. However, marital status was associated with grades 2–4 acute graft-versus-host ...
The primary goal of the HLA‐DPA1 ~ promoter ~ HLA‐DPB1 haplotype component of the 18th IHIWS was ... more The primary goal of the HLA‐DPA1 ~ promoter ~ HLA‐DPB1 haplotype component of the 18th IHIWS was to characterise the extended haplotypes within the HLA‐DP region and survey the extent of genetic diversity in this region across human populations. In this report, we analysed single‐nucleotide polymorphisms (SNPs) in 255 subjects from 6 different cohorts. The results from the HLA‐DP haplotype component have validated findings from the initial pilot study. SNPs in this region were inherited in strong linkage, particularly HLA‐DPA1, SNP‐linked promoter haplotypes and motifs in exon 2 of HLA‐DPB1. We reported 17 SNP‐linked haplotypes in the promoter region. Together with HLA‐DPA1 and HLA‐DPB1 alleles, they formed 74 distinct extended HLA‐DP haplotypes in 438 sequences. We also observed the presence of region‐specific alleles and promoter haplotypes. Our approach involved phasing extended SNPs including promoter SNPs, HLA‐DPA1 and HLA‐DPB1 alleles, in a 22 kb region, GRCh38/hg38 (chr6:33,0...
Background and Objectives. Donor helper T-lymphocytes may be involved in graft-versus-host diseas... more Background and Objectives. Donor helper T-lymphocytes may be involved in graft-versus-host disease (GVHD) and a graft-versus-leukemia effect after bone marrow transplantation (BMT). We assayed donor helper T-lymphocyte precursor frequencies (HTLPf) to see whether they could predict the severity of GVHD and disease relapse after transplantation, thereby facilitating donor selection, pre-transplant counselling and modification of GVHD prophylaxis after BMT.
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Papers by Janette Kwok