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  1. Gan GG, Phipps ME, Lee MM, Lu LS, Subramaniam RY, Bee PC, et al.
    Ann Hematol, 2011 Jun;90(6):635-41.
    PMID: 21110192 DOI: 10.1007/s00277-010-1119-6
    Within the Asian populations, Indian patients had been reported to require higher warfarin dose compared with the Chinese and Malay patients, and this could not entirely be explained by cytochrome P450 (CYP)2C9 gene variants. Genetic variants of vitamin K epoxide oxidase reductase complex subunit 1 (VKORC1) has been well established as one of key determinants in the different responses of warfarin amongst patients. Adult patients who attended an anticoagulation clinic with stable INR were recruited. VKORC1 and CYP2C9 genotype were sequenced, and clinical characteristics were assessed. A total of 91 Malays, 96 Chinese, and 46 Indian patients were recruited. The mean age was 55 years and 51.5% were males. The mean dose of warfarin for all patients was 3.7 mg, and the mean daily dose of warfarin was significantly higher in Indians compared with the Chinese and Malay patients, 4.9 versus 3.5 and 3.3 mg, respectively (p 
  2. Baskaran ND, Gan GG, Adeeba K
    Ann Hematol, 2008 Jul;87(7):563-9.
    PMID: 18437382 DOI: 10.1007/s00277-008-0487-7
    The purpose of this study was to determine if the Multinational Association for Supportive Care in Cancer (MASCC) risk-index score is able to predict the outcome of febrile neutropenia in patients with underlying hematological malignancy and to look at the other possible predictors of outcome. A retrospective study of 116 episodes of febrile neutropenia in patients who were admitted to the hematology ward of a local medical center in Malaysia between January 1st 2004 and January 31st 2005. Patient characteristics and the MASCC score were compared with outcome. The MASCC score predicted the outcome of febrile neutropenic episodes with a positive predictive value of 82.9%, a sensitivity of 93%, and specificity of 67%. Other predictors of a favorable outcome were those patients who had lymphomas versus leukemias, duration of neutropenia of less than 7 days, low burden of illness characterized by the absence of an infective focus and absence of lower respiratory tract infection, a serum albumin of >25 g/l, and the absence of gram-negative bacteremia on univariate analysis but only serum albumin level, low burden of illness, and presence of respiratory infection were significantly associated with unfavorable outcome after multivariate analysis. The MASCC score is a useful predictor of outcome in patients with febrile neutropenia with underlying hematological malignancies. This scoring system may be adapted for use in local settings to guide the clinical management of patients with this condition.
  3. Jackson N, Menon BS, Zarina W, Zawawi N, Naing NN
    Ann Hematol, 1999 May;78(5):233-6.
    PMID: 10391104
    Acute leukemia is more common in males at almost every age, and this fact remains unexplained. A study was carried out in northeast peninsular Malaysia, where the population is predominantly Malay, to examine whether there was a difference in ABO blood group distribution between males and females with acute leukemia (AL). The ABO blood groups of 109 male and 79 female patients with AL (98 ALL, 90 AML) were compared with those of 1019 controls. In the control population, 39.7% were group O. Among males with AL, 39.4% were group O, whereas among females with AL, the proportion was 24.1% (p=0.03). The same trend to a lower proportion of group O among females was seen if the group was divided into adult/pediatric or lymphoblastic/myeloblastic groups, though these differences were not statistically significant. If these findings can be confirmed, they suggest the presence of a "sex-responsive" gene near to the ABO gene locus on chromosome 9, which relatively protects group O women against AL, at least in our population. The existence of such a gene might also partly explain why acute leukemia, and possibly other childhood cancers, are more common in males.
  4. Reddy SC, Quah SH, Low HC, Jackson N
    Ann Hematol, 1998 Jan;76(1):15-8.
    PMID: 9486919
    Retinal changes are common in adult acute leukemia patients at presentation, but their prognostic significance is controversial. A 5-year study has been carried out with newly diagnosed acute leukemia patients aged 12-77 years. Seventy-seven cases (49 AML, 28 ALL) were studied prospectively for the presence of intraretinal hemorrhages (IRH), white-centered hemorrhages, cotton-wool spots, and macular hemorrhages. They were treated according to standard chemotherapy protocols, and then achievement of complete remission (CR) and the duration of overall survival (OS) were compared between the groups with and without these different retinal features. No association was found between the presence of any retinal abnormality and CR induction rate, although there was a trend to a lower CR rate among patients with IRH. The median OS of those with IRH was 72 days, compared with 345 days among those without IRH (p=0.002). A WBC at presentation greater than 50x10(9)/l and age greater than 40 years were also associated with shorter OS (p<0.0001 and p=0.0045, respectively). However, after regression analysis, IRH remained statistically significant as a poor prognostic indicator (p=0.01). We conclude that the presence of IRH is an indicator of poor prognosis in acute leukemia.
  5. Lai YK, Lai NM, Lee SW
    Ann Hematol, 2017 May;96(5):839-845.
    PMID: 28197721 DOI: 10.1007/s00277-017-2945-6
    Emerging epidemiological evidence suggests that patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency may have a higher risk of developing diabetes. The aim of the review was to synthesise the evidence on the association between G6PD deficiency and diabetes. A systematic search on Medline, EMBASE, AMED and CENTRAL databases for studies published between January 1966 and September 2016 that assessed the association between G6PD deficiency and diabetes was conducted. This was supplemented by a review of the reference list of retrieved articles. We extracted data on study characteristics, outcomes and performed an assessment on the methodological quality of the studies. A random-effects model was used to compute the summary risk estimates. Fifteen relevant publications involving 949,260 participants were identified, from which seven studies contributed to the meta-analysis. G6PD deficiency was associated with a higher odd of diabetes (odds ratio 2.37, 95% confidence interval 1.50-3.73). The odds ratio of diabetes among men was higher (2.22, 1.31-3.75) compared to women (1.87, 1.12-3.12). This association was broadly consistent in the sensitivity analysis. Current evidence suggests that G6PD deficiency may be a risk factor for diabetes, with higher odds among men compared to women. Further research is needed to determine how G6PD deficiency moderates diabetes.
  6. Azman NF, Abdullah WZ, Hanafi S, Diana R, Bahar R, Johan MF, et al.
    Ann Hematol, 2020 Apr;99(4):729-735.
    PMID: 32078010 DOI: 10.1007/s00277-020-03927-5
    HbE/Beta thalassemia (HbE/β-thalassemia) is one of the common genetic disorders in South East Asia. It is heterogeneous in its clinical presentation and molecular defects. There are genetic modifiers which have been reported to influence the disease severity of this disorder. The aim of this study was to determine the genetic polymorphisms which were responsible for the disease clinical diversity. A case-control study was conducted among Malay transfusion-dependent HbE/β-thalassemia patients. Patients who were confirmed HbE/β-thalassemia were recruited and genotyping study was performed on these subjects. Ninety-eight patients were selected and divided into moderate and severe groups based on clinical parameters using Sripichai scoring system (based on hemoglobin level, spleen size, growth development, the age of first transfusion and age of disease presentation). Forty-three (44.9%) and 55 (56.1%) patients were found to have moderate and severe clinical presentation, respectively. Genotyping analysis was performed using Affymetrix 6.0 microarray platform. The SNPs were filtered using PLINK and Manhattan plot by R software. From the GWAS results, 20 most significant SNPs were selected based on disease severity when compared between moderate and severe groups. The significant SNPs found in this study were mostly related to thalassemia complications such as rs7372408, associated with KCNMB2-AS1 and SNPs associated with disease severity. These findings could be used as genetic predictors in managing patients with HbE/β-thalassemia and served as platform for future study.
  7. Chia WC, Khoo TS, Abdul Wahid SFS, Razak NFA, Alauddin H, Raja Sabudin RZA, et al.
    Ann Hematol, 2019 May;98(5):1279-1291.
    PMID: 30783731 DOI: 10.1007/s00277-019-03626-w
    Short tandem repeat (STR) analysis is used in chimerism monitoring after allogeneic hematopoietic stem cell transplantation (HSCT) for patients with various hematologic malignancies. Commercial forensic STR kits often contain loci with huge differences in power of discrimination (PD) across populations, causing some loci to be less informative for chimerism analysis in certain populations. This study aimed to construct a new STR multiplex panel with highly informative loci for efficient chimerism analysis. Thirteen STR markers which exhibit high PD (> 0.9) in at least 80% of 50 populations globally were selected to form a new panel and used in STR analysis of 253 Malaysian subjects. Cumulative power of discrimination (CPD) and combined power of exclusion (CPE) were determined from 253 Malaysian individuals. Loci informativity was assessed and compared to the commercial AmpFLSTR Identifiler PCR Amplification kit in 14 donor-recipient pairs. The new panel had detected 202 unique alleles including five novel alleles from the 253 individuals with high CPD and CPE (> 0.99999999999999999 and > 0.999999997 respectively). All loci from the new panel in the donor-recipient pair analysis showed higher than 50% informativity, while five loci from the commercial kit demonstrated lower than 50% informativity. Four loci from the new panel ranked the highest informativity. A sequenced allelic ladder which consists of 202 unique alleles from the 253 subjects was also developed to ensure accurate allele designation. The new 13-loci STR panel, thus, could serve as an additional powerful, accurate, and highly informative panel for chimerism analysis for HSCT patients.
  8. Abdullah N, Ismail N, Abd Jalal N, Mohd Radin F, Othman R, Kamalul Arifin AS, et al.
    Ann Hematol, 2020 Nov;99(11):2521-2527.
    PMID: 32975589 DOI: 10.1007/s00277-020-04279-w
    This study was aimed at determining the prevalence of anaemia amongst the Malaysian Cohort participants and the associated risk factors. This was a cross-sectional study that involved 102,388 participants from The Malaysian Cohort (TMC) aged between 35 and 70 years old recruited from April 2006 to September 2012. Venous blood was taken for the full blood count. The prevalence of anaemia was 13.8% with majority having the microcytic-hypochromic type (59.7%). Comparison between the ethnic groups showed that Indians have the highest prevalence of anaemia (19.9%), followed by Malays (13.1%), and Chinese (12.0%). The prevalence of anaemia was substantially higher in females (20.1%) compared to males (4.9%). Amongst the female participants, the prevalence of anaemia was highest amongst those who were younger than 49 years old and decreased as the age increased. In contrast, the prevalence of anaemia in males increased with age. Gender, ethnicity, age, marital status, presence of platelet disorders and kidney disease were significant risk factors associated with anaemia and contributed to 14.9% of the risk of developing anaemia in this population. The prevalence of anaemia amongst the Malaysian Cohort participants is 13.8% with the majority having the microcytic and hypochromic type implying iron deficiency as the main cause. It is important that those who have anaemia be further investigated and treated.
    Study name: The Malaysian Cohort (TMC) project
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