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  1. Kuan JW, Melaine Michael S
    Med J Malaysia, 2018 04;73(2):78-85.
    PMID: 29703870 MyJurnal
    OBJECTIVES: There are very few published chronic myeloid leukaemia (CML) epidemiology studies in South-East Asia and no representative from Malaysia.

    METHODS: This is a cross-sectional study of adult CML patients (citizen) in a single but representative centre in southern Sarawak.

    RESULTS: Total 79 patients (Malay 39%, Chinese 30.4%, Iban 17.7%, Bidayuh 12.7%) were identified from the databases. Median age at diagnosis was younger, 40, compared to developed countries due to population structure. M:F ratio was higher, 2.6:1 compared to other countries 1.3-1.7:1. Majority presented at chronic phase (89.5%), low/intermediate risk score (80%) and started imatinib (96%) as first line tyrosine kinase inhibitor (TKI), which 40% of them switched to other TKI due to intolerance (17%) and failure (including disease progression)/not achieving major molecular response (83%). Quantitative polymerase chain reaction (qPCR) assessment after three months of TKI treatment had higher positive predictive value to predict Imatinib failure, 75%, than qPCR assessment after six months of TKI treatment, 58%. Presenting phase, symptoms, signs and laboratory data were like most countries. Estimated prevalence and incidence of CML in southern Sarawak was 69.2/1,000,000 population at the Year 2016 (similar to most developing countries) and 8.0/1,000,000 population per year at the Year 2011-2016 (similar to most countries), respectively. The incidence increased with age and was lowest among Iban, 12.8 and highest among Chinese, 19.5, which was 4x higher than Chinese in China. The prevalence of different BCR-ABL1 transcript type was like other Asia countries CONCLUSION: Significant epidemiological differences on M:F ratio and ethnic groups compared to other countries warrant further study.

  2. Kuan JW, Su AT, Leong CF
    J Clin Apher, 2017 Dec;32(6):517-542.
    PMID: 28485020 DOI: 10.1002/jca.21550
    Granulocyte-colony stimulating factor (G-CSF) mobilizes and increases the amount of hematopoietic stem cells in peripheral blood, enabling its harvest by few apheresis procedures. The pegylated G-CSF has longer half-life and is given once only, which is more comfortable for patients, whereas the non-pegylated requires multiple daily injection because of its short half-life. We summarized results of randomized trials comparing the efficacy and safety of pegylated and non-pegylated G-CSF for peripheral blood stem cell mobilization. We searched the Cochrane CENTRAL, MEDLINE, EMBASE, and two conference proceedings. Two authors made the selection, extracted data and evaluated methodological quality using GRADE independently. We used random-effects model for meta-analysis. We found 3956 records and retrieved 47 full texts. We included eight randomized trials with a total number of 554 randomized and 532 analyzed subjects. The meta-analysis included five trials because not all trials reported the same outcomes. Pooling data from two studies shows no evidence for a difference in the successful mobilization rate (CD34+ cell ≥ 2 × 106 /kg collected) between pegfilgrastim 6 mg (early administration) and filgrastim 5 µg/kg/day (147 participants; risk ratio (RR) 0.87, 95% confidence interval (95%CI) 0.67-1.11; P = .26). Pooling data from three studies shows no difference in the incidence of adverse events between pegylated and non-pegylated G-CSF (170 participants; RR 0.86, 95%CI 0.34-2.17; P = .75). No difference found on the quantity of CD34+ cells collected, number of apheresis procedure in successful mobilization, level of peak PB CD34+ cells achieved, and day of neutrophil and platelet engraftment.
  3. Su AT, Xavier G, Kuan JW
    PLoS One, 2023;18(7):e0287999.
    PMID: 37406016 DOI: 10.1371/journal.pone.0287999
    This study aimed to measure the spectral power differences in the brain rhythms among a group of hospital doctors before and after an overnight on-call duty. Thirty-two healthy doctors who performed regular on-call duty in a tertiary hospital in Sarawak, Malaysia were voluntarily recruited into this study. All participants were interviewed to collect relevant background information, followed by a self-administered questionnaire using Chalder Fatigue Scale and electroencephalogram test before and after an overnight on-call duty. The average overnight sleep duration during the on-call period was 2.2 hours (p<0.001, significantly shorter than usual sleep duration) among the participants. The mean (SD) Chalder Fatigue Scale score of the participants were 10.8 (5.3) before on-call and 18.4 (6.6) after on-call (p-value < 0.001). The theta rhythm showed significant increase in spectral power globally after an overnight on-call duty, especially when measured at eye closure. In contrast, the alpha and beta rhythms showed reduction in spectral power, significantly at temporal region, at eye closure, following an overnight on-call duty. These effects are more statistically significant when we derived the respective relative theta, alpha, and beta values. The finding of this study could be useful for development of electroencephalogram screening tool to detect mental fatigue.
  4. Kuan JW, Pathmanathan R, Chang KM, Tan SM
    Leuk. Res., 2009 Nov;33(11):1574-7.
    PMID: 19215983 DOI: 10.1016/j.leukres.2009.01.016
    Granulocytic sarcoma (GS) can occur de novo or in association with intramedullary myeloid disorders. With the advent of sophisticated molecular detection techniques to detect diagnostic genes such as bcr-abl, PML-RARA and CBFB/MYH11 in bone marrow or peripheral blood, many cases of the so called 'primary' GS are questionable. We report a case of primary GS where the tumor mass bcr-abl translocation was demonstrated by fluorescent in situ hybridization in which there was no evidence of chronic myeloid leukemia (CML). This is an important finding as it highlights the possibility that CML may present as a sole extramedullary form, and illustrates potential treatment by tyrosine kinase inhibitor.
  5. Su AT, Kuan JW, Shanat M, Baderin OS, Haalah M
    Med J Malaysia, 2023 Sep;78(5):621-626.
    PMID: 37775489
    INTRODUCTION: Financial affordability to purchase commodities for disease prevention is an important public health issue. The objective of this paper is to report the financial affordability and willingness to pay amongst the parents of government students for their children's nonmedical mask use, using a newly created Household Face Mask Affordability Questionnaire (MAQ).

    MATERIALS AND METHODS: This was a cross-sectional study involving the parents or guardians of 50.6% (44/87) government schools in the whole of Kuching Division of Sarawak. The sampling method was multistage cluster sampling, whereby stage one involved random sampling of 49.2% (30/61) primary schools and 53.8% (14/46) secondary schools in the Kuching Division, followed by stage two cluster sampling of one class per non-examination standard in each randomly sampled school. All students in the sampled classes were asked to bring a face-validated questionnaire (MAQ) back home to be answered by one of their parents or a guardian. A total of 2559 out of 3661 distributed questionnaires were collected, with a response rate of 70%. The data collection period was between April and June of 2022 so as the recall bias of the information collected, especially on the actual spending on the face masks for the school going students, was minimised. The relevant summary statistics for self-perceived face masks characteristics, face mask expenses, affordability and willingness to pay were calculated. We regress separately the monthly affordability and willingness to pay amount against age, occupation, marital status, total number of children, monthly income and monthly saving to build predictive models for affordability and willingness to pay amount per child per month.

    RESULTS: The average Scale-level Face Validity Indexes for all aspects of validity (clarity, comprehension, relevancy, representativeness) are high (0.91 to 1.00) for MAQ. Most of the respondents were mothers, married, working as private employees with a mean age of 41 and belonged to the B40 and M40 group. The average monthly saving per family was RM540, which was about 15% of the total income. The average actual monthly spending to purchase face masks for one child is RM24. On average, a family can afford to pay RM23.80 for one child per month to purchase face masks. The willingness to pay for the same was RM25.27. The median affordability, willingness to pay and actual spending for face masks per child was RM16.67 per month. Taking 75th percentile as the reasonable maximum expenses per child for face masks per month, the affordable amount by most parents is RM30, with the willingness to pay at 10% higher. Affordability to purchase a face mask is influenced by the marital status, occupation, income, saving and the number of dependent of the breadwinner of a household. The most important face mask characteristics expected by the parents are better filtration efficiency and easier breathability.

    CONCLUSION: The affordability and willingness to pay the amount to purchase face masks amongst parents of government students in Sarawak were RM30 and RM33 per child per month, respectively.

  6. Kuan JW, Su AT, Tay SP, Fong IL, Kubota S, Su'ut L, et al.
    Int J Hematol, 2020 Feb;111(2):217-224.
    PMID: 31707540 DOI: 10.1007/s12185-019-02768-x
    The BCR-ABL1 fusion gene is the driver mutation of Philadelphia chromosome-positive chronic myeloid leukemia (CML). Its expression level in CML patients is monitored by a real-time quantitative polymerase chain reaction defined by the International Scale (qPCRIS). BCR-ABL1 has also been found in asymptomatic normal individuals using a non-qPCRIS method. In the present study, we examined the prevalence of BCR-ABL1 in a normal population in southern Sarawak by performing qPCRIS for BCR-ABL1 with ABL1 as an internal control on total white blood cells, using an unbiased sampling method. While 146 of 190 (76.8%) or 102 of 190 (53.7%) samples showed sufficient amplification of the ABL1 gene at > 20,000 or > 100,000 copy numbers, respectively, in qPCRIS, one of the 190 samples showed amplification of BCR-ABL1 with positive qPCRIS of 0.0023% and 0.0032% in two independent experiments, the sequence of which was the BCR-ABL1 e13a2 transcript. Thus, we herein demonstrated that the BCR-ABL1 fusion gene is expected to be present in approximately 0.5-1% of normal individuals in southern Sarawak.
  7. Kuan JW, Su AT, Leong CF, Osato M, Sashida G
    Acta Haematol., 2020;143(2):96-111.
    PMID: 31401626 DOI: 10.1159/000501146
    The treatment of chronic myeloid leukaemia (CML) requires quantitative polymerase chain reaction (qPCR) to monitor BCR-ABL1 in International Scale (IS). Some normal subjects were found to harbour BCR-ABL1. We performed a systematic review on normal subjects harbouring BCR-ABL1. A literature search was done on July 16, 2017 using EBSCOhost Research Databases interface and Western Pacific Region Index Medicus. Two authors selected the studies, extracted the data, and evaluated the quality of studies using the modified Appraisal Tool for Cross-Sectional Studies independently. The outcomes were prevalence, level of BCR-ABL1IS, proportion, and time of progression to CML. The initial search returned 4,770 studies. Eleven studies, all having used convenient sampling, were included, with total of 1,360 subjects. Ten studies used qualitative PCR and one used qPCR (not IS). The mean prevalence of M-BCR was 5.9, 15.5, and 15.9% in cord blood/newborns/infants (CB/NB/I) (n = 170), children (n = 90), and adults (n = 454), respectively, while m-BCR was 15, 26.9, and 23.1% in CB/NB/I (n = 786), children (n = 67), and adults (n = 208), respectively. No study reported the proportion and time of progression to CML. Nine studies were graded as moderate quality, one study as poor quality, and one study as unacceptable. The result of the studies could neither be inferred to the general normal population nor compared. Follow-up data were scarce.
  8. Kuan JW, Su AT, Leong CF, Osato M, Sashida G
    Int J Hematol, 2019 Jan;109(1):130.
    PMID: 30406326 DOI: 10.1007/s12185-018-2556-6
    The author would like to correct the error in the publication of the original article. The corrected detail is given below for your reading.
  9. Kuan JW, Law CS, Wong XQ, Ko CT, Awang ZH, Chew LP, et al.
    Appl Radiat Isot, 2016 Oct;116:13-21.
    PMID: 27472826 DOI: 10.1016/j.apradiso.2016.07.016
    Radioimmunotherapy is an established treatment modality in Non-Hodgkin's lymphoma. The only two commercially available radioimmunotherapies - (90)Y-ibritumomab tiuxetan is expensive and (131)I-tositumomab has been discontinued from commercial production. In resource limited environment, self-labelling (131)I-rituximab might be the only viable practical option. We reported our pioneer experience in Malaysia on self-labelling (131)I-rituximab, substituting autologous haematopoietic stem cell transplantation (HSCT) and a patient, the first reported case, received high dose (131)I-rituximab (6000MBq/163mCi) combined with BEAM conditioning for autologous HSCT.
  10. Kuan JW, Chang KM, Phan CL, Wong SP, Lim SM, Toh SG, et al.
    Med J Malaysia, 2021 May;76(3):414-416.
    PMID: 34031342
    Fluctuation of BCR-ABL1 real-time quantitative polymerase chain reaction in International Scale (qPCRIS) level below major molecular response (MMR) (0.1%IS) is a known phenomenon after stopping tyrosine kinase inhibitor (TKI) in chronic myeloid leukaemia (CML) patients who are attempting treatment free remission (TFR). We report here four cases of fluctuation beyond MMR during conduct of a Malaysia Stop TKI Trial (MSIT) to examine the validity of the commonly used relapse criterion - loss of MMR for one reading - aiming to provide evidence in setting relapse criteria for future CML patients who want to attempt TFR.
  11. Kuan JW, Su AT, Wahab M, Hamdan A, Hashim J, Kiyu A, et al.
    BMC Cancer, 2023 Jun 19;23(1):563.
    PMID: 37337159 DOI: 10.1186/s12885-023-10988-y
    BACKGROUND: Published epidemiological studies of haematological cancers are few. Hereby we present a 20-year epidemiological data of haematological cancers in Sarawak from a population-based cancer registry.

    METHODS: Haematological cancer cases with ICD-10 coded C81-C96 and ICD-O coded /3 diagnosed from 1996 to 2015 were retrieved from Sarawak Cancer Registry. Adult was defined as those 15 years and above. Incidence rate (IR) was calculated based on yearly Sarawak citizen population stratified to age, gender, and ethnic groups. Age-standardised IR (ASR) was calculated using Segi World Standard Population.

    RESULTS: A total of 3,947 cases were retrieved and analysed. ASR was 10 and male predominance (IR ratio 1.32, 95%CI 1.24,1.41). Haematological cancers generally had a U-shaped distribution with lowest IR at age 10-14 years and exponential increment from age 40 years onwards, except acute lymphoblastic leukaemia (ALL) with highest IR in paediatric 2.8 versus adult 0.5. There was a significant difference in ethnic and specific categories of haematological cancers, of which, in general, Bidayuh (IR ratio 1.13, 95%CI 1.00, 1.27) and Melanau (IR ratio 0.54, 95%CI 0.45, 0.65) had the highest and lowest ethnic-specific IR, respectively, in comparison to Malay. The ASR (non-Hodgkin lymphoma, acute myeloid leukaemia, ALL, chronic myeloid leukaemia, and plasma cell neoplasm) showed a decreasing trend over the 20 years, -2.09 in general, while Hodgkin lymphoma showed an increasing trend of + 2.80. There was crude rate difference between the 11 administrative divisions of Sarawak.

    CONCLUSIONS: This study provided the IR and ASR of haematological cancers in Sarawak for comparison to other regions of the world. Ethnic diversity in Sarawak resulted in significant differences in IR and ASR.

  12. Kuan JW, Su AT, Leong CF, Osato M, Sashida G
    Int J Hematol, 2018 Nov;108(5):465-484.
    PMID: 30218276 DOI: 10.1007/s12185-018-2528-x
    BACKGROUND: Studies of a provisional entity pre-clinical chronic myeloid leukaemia (CML), which precedes chronic phase (CP) without leucocytosis or blood/marrow feature of CML CP, has been increasing.

    OBJECTIVE: To perform a systematic review of pre-clinical CML and analysis the data relevant to disease progression to CML CP.

    METHOD: We performed a literature search on 16 July 2017 using EBSCOhost Research Databases interface and Western Pacific Region Index Medicus. Two authors selected the studies, extracted the data and evaluated the quality of studies using an 8-item tool, independently. The outcomes were percentage of Philadelphia chromosome in the number of metaphases examined (Ph%), correlation between Ph% and blood count and time progress to CML.

    RESULT: Our initial search returned 4770 studies. A total of 10 studies with a total 17 subjects were included. The lowest Ph%, which eventually progresses to CML, was 10%. Absolute basophil count seemed to correlate better with Ph% compared to total white cell and absolute eosinophil count. The time from the first documented pre-clinical CML to CML ranged from 12 to 48 months. The overall quality of the included studies was average.

    CONCLUSION: This is the first systematic review on pre-clinical CML. This entity requires additional large-scale studies.

  13. Kuan JW, Su AT, Wong SP, Sim XY, Toh SG, Ong TC, et al.
    Transfus Apher Sci, 2015 Oct;53(2):196-204.
    PMID: 25910537 DOI: 10.1016/j.transci.2015.03.017
    There are few randomized trials comparing filgrastim and pegfilgrastim in peripheral blood stem cell mobilization (PBSCM). None of the trials studied the effects of the timing of pegfilgrastim administration on the outcomes of mobilization. We conducted a randomized triple blind control trial comparing the outcomes of filgrastim 5 µg/kg daily from day 3 onwards, 'early' pegfilgrastim 6 mg on day 3 and 'delayed' pegfilgrastim 6 mg on day 7 in cyclophosphamide PBSCM in patients with no previous history of mobilization. Peripheral blood (PB) CD34+ cell count was checked on day 8 and day 11 onward. Apheresis was started when PB CD34+ ≥ 10/µl from day 11 onward. The primary outcome was the successful mobilization rate, defined as cumulative collection of ≥2 × 10(6)/kg CD34+ cells in three or less apheresis. The secondary outcomes were the day of neutrophil and platelet engraftment post transplantation. There were 156 patients randomized and 134 patients' data analyzed. Pegfilgrastim 6 mg day 7 produced highest percentage of successful mobilization, 34 out of 48 (70.8%) analyzed patients, followed by daily filgrastim, 28 out of 44 (63.6%) and day 3 pegfilgrastim, 20 out of 42 (47.6%) (p = 0.075). Pegfilgrastim day 7 and daily filgrastim reported 1.48 (p = 0.014) and 1.49 (p = 0.013) times higher successful mobilization rate respectively as compared to pegfilgrastim day 3 after adjusting for disease, gender and exposure to myelotoxic agent. Multiple myeloma patients were three times more likely to achieve successful mobilization as compared to acute leukemia or lymphoma patients. Pegfilgrastim avoided the overshoot of white cells compared to filgrastim. There was no difference in the duration of both white cells and platelet recovery post transplantation between the three interventional arms.
  14. Ting CY, Chang KM, Kuan JW, Sathar J, Chew LP, Wong OJ, et al.
    Int J Med Sci, 2019;16(4):556-566.
    PMID: 31171907 DOI: 10.7150/ijms.27610
    Background: Clinical significance of germinal center B-cell (GCB) and non-GCB sub-categorization, expression of MYC, BCL2, BCL6, CD5 proteins and Epstein Barr virus encoded RNA (EBER) positivity in diffuse large B-cell lymphoma (DLBCL) remain controversial. Could these biomarkers accurately identify high risk DLBCL patients? Are MYC, BCL2 and BCL6 proteins expression feasible as baseline testing to predict c-Myc, BCL2 or BCL6 gene rearrangements? Aims: To investigate prognostic values of GCB/non-GCB sub-categorization, Double Protein Expression Lymphoma (DPL), Triple Protein Expression Lymphoma (TPL), positivity of CD5 protein and EBER in patients with DLBCL disease. To evaluate correlation between BCL2 , c-Myc and BCL6 gene rearrangements with BCL2, MYC and BCL6 proteins expression. Methods: Diagnostic tissue samples of 120 DLBCL patients between January 2012 to December 2013 from four major hospitals in Malaysia were selected. Samples were subjected to immunohistochemical staining, fluorescent in-situ hybridization (FISH) testing, and central pathological review. Pathological data were correlated with clinical characteristics and treatment outcome. Results: A total of 120 cases were analysed. Mean age of diagnosis was 54.1 years ± 14.6, 64 were males, 56 were females, mean follow up period was 25 months (ranged from 1 to 36 months). Of the 120 cases, 74.2% were non-GCB whereas 25.8% were GCB, 6.7% were EBER positive, 6.7% expressed CD5 protein, 13.3% were DPL and 40% were TPL. The prevalence of c-Myc, BCL2, BCL6 gene rearrangements were 5.8%, 5.8%, and 14.2%, respectively; and 1.6% were Double Hit Lymphoma (DHL). EBER positivity, DPL, TPL, c-Myc gene rearrangement, BCL2 gene rearrangement, extra copies of BCL2 gene and BCL6 gene rearrangement were associated with shorter median overall survival (P<0.05). IPI score was the significant determinants of median overall survival in DPL and TPL (P<0.05). CD5 protein expression and GCB/non-GCB sub-categorization did not affect treatment outcome (P>0.05). Overall, c-Myc, BCL2 and BCL6 gene rearrangements showed weak correlation with expression of MYC, BCL2 and BCL6 proteins (P>0.05). Fluorescent in situ hybridization is the preferred technique for prediction of treatment outcome in DLBCL patients. Conclusion:c-Myc, BCL2, and BCL6 gene rearrangements, EBER expression, DHL, TPL and IPI score are reliable risk stratification tools. MYC, BCL2 and BCL6 proteins expression are not applicable as baseline biomarkers to predict c-Myc, BCL2, and BCL6 gene rearrangements.
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