Displaying publications 21 - 40 of 51 in total

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  1. Mortality outcomes and survival patterns of patients with myeloproliferative neoplasms in Malaysia
    Yap YY, Sathar J, Law KB, MPN registry working group
    Cancer Causes Control, 2022 Feb;33(2):343-351.
    PMID: 34846616 DOI: 10.1007/s10552-021-01521-2
    BACKGROUND: Prognostication of myeloproliferative neoplasm (MPN) has always been challenging, even with the advent of Janus kinase 2 (JAK2 V617F) molecular studies. The survival pattern of patients diagnosed with MPN in developing countries is still undetermined.

    MATERIALS AND METHODS: The national MPN registry conducted from 2009 to 2015 in Malaysia provided a comprehensive insight into the demographics, clinical characteristics and laboratory parameters of patients diagnosed with MPN nationwide. The study analysed the survival patterns and mortality outcomes and risk among 671 patients diagnosed with essential thrombocythaemia (ET), polycythaemia vera (PV), primary myelofibrosis (PMF) and unclassified MPN (MPN-U). Mortality status was traced and confirmed until the end of December 2018, with right censoring applied to patients alive beyond that.

    RESULTS: The analysed cohort consisted of 283 (42.2%) ET, 269 (40.1%) PV, 62 (9.2%) PMF and 57 (8.5%) MPN-U incident cases with diagnosis made between 2007 and 2015. The majority of patients were male (52.3%) and Malay (48.9%), except for ET, in which the majority of patients were female (60.1%) and of Chinese origin (47.0%). Female patients were found to have significantly better overall survival (OS) rates in ET (p = 0.0285) and MPN-U (p = 0.0070). Patients with JAK2 V617F mutation were found to have marginally inferior OS over time. Multivariable Cox regression identified patients with increased age [hazard ratio (HR) 1.055, 95% CI 1.031; 1.064], reduced haemoglobin (HB) level (HR 0.886, 95% CI 0.831; 0.945, p = 0.0002), being male (HR 1.545, 95% CI 1.077; 2.217, p = 0.0182), and having MPN-U (HR 2.383, 95% CI 1.261; 4.503, p = 0.0075) and PMF (HR 1.975, 95% CI 1.054; 3.701, p = 0.0335) at increased risk for worse mortality outcomes.

    CONCLUSION: Myeloproliferative neoplasm reduces patient survival. The degree of impact on survival varies according to sub-type, sex, bone marrow fibrosis and HB levels. The JAK2 V617F mutation was not found to affect the survival pattern or mortality outcome significantly.

  2. Fulltext A Comparison of the Incidence Rate for Joint Bleeding and FVIII Consumption between On-Demand versus Prophylaxis Factor VIII Replacement Therapy and the Direct Cost of Prophylaxis Treatment in Severe Haemophilia A Patients
    Jamal M, Sathar J, Jamari J, Mohd Saffian S
    Malays J Med Sci, 2023 Feb;30(1):129-136.
    PMID: 36875203 DOI: 10.21315/mjms2023.30.1.11
    BACKGROUND: Haemophilia A is a bleeding disorder caused by inadequate clotting factor VIII (FVIII). There are two main modes of treatment approach in severe haemophilia A patients either with on-demand or prophylaxis therapy with clotting factor FVIII concentrates. In this study, a comparison was made between the bleeding incidence rate of the on-demand and prophylaxis group in severe haemophilia A patients at Ampang Hospital, Malaysia.

    METHODS: A retrospective study involving patients with severe haemophilia was conducted. The patient's self-reported bleeding frequency was retrieved from the patient's treatment folder from January to December 2019.

    RESULTS: Fourteen patients received on-demand therapy, while the other 24 patients received prophylaxis treatment. The total number of joint bleeds in the prophylaxis group was significantly lower compared to the on-demand group (2.79 bleeds versus 21.36 bleeds [P < 0.001]). Furthermore, the total annual usage of FVIII was higher in the prophylaxis group compared to the on-demand group (1,506 IU/kg/year [± 905.98] versus 365.26 IU/kg/year [± 223.90], P = 0.001).

    CONCLUSION: Prophylaxis FVIII therapy is an effective treatment in reducing the frequency of bleeding joints. However, this treatment approach is associated with high cost due to the high consumption of FVIII.

  3. α-Haemoglobin stabilising protein expression is influenced by mean cell haemoglobin and HbF levels in HbE/β-thalassaemia individuals
    Lim WF, Muniandi L, George E, Sathar J, Teh LK, Gan GG, et al.
    Blood Cells Mol. Dis., 2012 Jan 15;48(1):17-21.
    PMID: 22079025 DOI: 10.1016/j.bcmd.2011.10.002
    The alpha haemoglobin stabilising protein (AHSP) acts as a molecular chaperone for α-globin by stabilising nascent α-globin before transferring it to waiting free β-globin chains. Binding of AHSP to α-globin renders α-globin chemically inert whereby preventing it from precipitating and forming reactive oxygen species byproducts. The AHSP has been actively studied in the recent years, particularly in its relation to β-thalassaemia. Studies have shown that AHSP is a modifier in β-thalassaemia mice models. However, this relationship is less established in humans. Studies by some groups showed no correlation between the AHSP haplotypes and the severity of β-thalassaemia, whereas others have shown that certain AHSP haplotype could modify the phenotype of β-thalassaemia intermedia patients. We investigated the expression of AHSP in relation to selected demographic data, full blood count, HPLC results, HbE/β-thalassaemia genotype, Xmn-1 Gγ polymorphism, α-globin, β-globin and γ-globin expression. We found that AHSP expression was significantly correlated to mean cell haemoglobin level, HbF %, α-globin, β-globin and excess α-globin expression. We concluded that AHSP could be a secondary compensatory mechanism in red blood cells to counterbalance the excess α-globin chains in HbE/β-thalassaemia individuals.
  4. Fulltext Correlation of BACH1 and Hemoglobin E/Beta-Thalassemia Globin Expression
    Lee TY, Muniandy L, Teh LK, Abdullah M, George E, Sathar J, et al.
    Turk J Haematol, 2016 Mar 05;33(1):15-20.
    PMID: 26377036 DOI: 10.4274/tjh.2014.0197
    The diverse clinical phenotype of hemoglobin E (HbE)/β-thalassemia has not only confounded clinicians in matters of patient management but has also led scientists to investigate the complex mechanisms involved in maintaining the delicate red cell environment where, even with apparent similarities of α- and β-globin genotypes, the phenotype tells a different story. The BTB and CNC homology 1 (BACH1) protein is known to regulate α- and β-globin gene transcriptions during the terminal differentiation of erythroid cells. With the mutations involved in HbE/β-thalassemia disorder, we studied the role of BACH1 in compensating for the globin chain imbalance, albeit for fine-tuning purposes.
  5. Fulltext Fatal Delayed Haemolytic Transfusion Reaction and Hyperhaemolysis Syndrome in a Pregnant Woman with Sickle Cell Anaemia
    Asnawi AW, Sathar J, Mohamed R, Deraman R, Kumaran S, Hamid SS, et al.
    Indian J Hematol Blood Transfus, 2016 Jun;32(Suppl 1):251-3.
    PMID: 27408406 DOI: 10.1007/s12288-014-0495-9
    Clinical manifestations of sickle cell disease (SCD) arise from the tendency of the sickle haemoglobin to polymerize and deform red blood cells into the characteristic sickle shape. Sickle cell crisis is a devastating complication that may occur in patients with SCD. If not managed properly permanent organ damage and even death may be the final outcome. A case of a 32-year-old Nigerian lady, Gravida 1 Para 0 in her first trimester, with SCD who developed signs and symptoms of delayed haemolytic transfusion reaction after receiving packed red cell transfusion is demonstrated. Multiple red cell alloantibodies were detected in the patient's plasma; anti-Fy a, anti-Jk b and anti-E. The patient miscarriaged and succumbed to complications of hyperhaemolysis with delayed haemolytic transfusion reaction, acute chest syndrome and renal failure. There is an urgent need for mandatory red cell antibody screen and identification especially in high-risk cases. Prevention of alloimmunization by supplying phenotype-specific red cells is also required.
  6. Fulltext Clinical characteristics and outcomes of thrombotic microangiopathy in Malaysia
    Yap YY, Sathar J, Law KB, Zulkurnain PAB, Edmund SC, Chang KM, et al.
    Blood Res, 2018 Jun;53(2):130-137.
    PMID: 29963519 DOI: 10.5045/br.2018.53.2.130
    Background: Thrombotic microangiopathy (TMA) with non-deficient ADAMTS-13 (a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13) outcome is unknown hence the survival analysis correlating with ADAMTS-13 activity is conducted in Malaysia.

    Methods: This was a retrospective epidemiological study involving all cases of TMA from 2012-2016.

    Results: We evaluated 243 patients with a median age of 34.2 years; 57.6% were female. Majority of the patients were Malay (62.5%), followed by Chinese (23.5%) and Indian (8.6%). The proportion of patients with thrombotic thrombocytopenic purpura (TTP) was 20.9%, 72.2% of which were acquired while 27.8% were congenital. Patients with ADAMTS-13 activity ≥5% had a four-fold higher odds of mortality compared to those with ADAMTS-13 activity <5% (odds ratio: 4.133, P=0.0425). The mortality rate was 22.6% (N=55). Most cases had secondary etiologies (42.5%), followed by acquired TTP (16.6%), atypical hemolytic uremic syndrome (HUS) or HUS (12.8%) and congenital TTP (6.4%). Patients with secondary TMA had inferior overall survival (P=0.0387). The secondary causes comprised systemic lupus erythematosus (30%), infection (29%), pregnancy (10%), transplant (8%), malignancy (6%), and drugs (3%). Transplant-associated TMA had the worst OS (P=0.0016) among the secondary causes. Plasma exchange, methylprednisolone and intravenous immunoglobulin were recorded as first-line treatments in 162 patients, while rituximab, bortezomib, vincristine, azathioprine, cyclophosphamide, cyclosporine, and tacrolimus were described in 78 patients as second-line treatment.

    Conclusion: This study showed that TMA without ADAMTS-13 deficiency yielded inferior outcomes compared to TMA with severeADAMTS-13 deficiency, although this difference was not statistically significant.

  7. Fulltext A Novel Algorithm Using Cell Population Data (VCS Parameters) as a Screening Discriminant between Alpha and Beta Thalassemia Traits
    Ambayya A, Sahibon S, Yang TW, Zhang QY, Hassan R, Sathar J
    Diagnostics (Basel), 2021 Nov 22;11(11).
    PMID: 34829510 DOI: 10.3390/diagnostics11112163
    Thalassemia is one of the major inherited haematological disorders in the Southeast Asia region. This study explored the potential utility of red blood cell (RBC) parameters and reticulocyte cell population data (CPD) parameters in the differential diagnosis of α and β-thalassaemia traits as a rapid and cost-effective tool for screening of thalassemia traits. In this study, a total of 1597 subjects (1394 apparently healthy subjects, 155 subjects with α-thalassaemia trait, and 48 subjects with β-thalassaemia trait) were accrued. The parameters studied were the RBC parameters and reticulocyte CPD parameters derived from Unicel DxH800. A novel algorithm named αβ-algorithm was developed: (MN-LMALS-RET × RDW) - MCH) to discriminate α from β-thalassaemia trait with a cut-off value of 1742.5 [AUC = 0.966, sensitivity = 92%, specificity = 90%, 95% CI = 0.94-0.99]. Two prospective studies were carried: an in-house cohort to assess the specificity of this algorithm in 310 samples comprising various RBC disorders and in an interlaboratory cohort of 65 α-thalassemia trait, and 30 β-thalassaemia trait subjects to assess the reproducibility of the findings. We propose the αβ-algorithm to serve as a rapid, inexpensive surrogate evaluation tool of α and β-thalassaemia in the population screening of thalassemia traits in geographic regions with a high burden of these inherited blood disorders.
  8. Fulltext Health-related quality of life using EQ-5D among chronic myeloid leukaemia patients in health centres in Klang Valley, Malaysia
    Wan Puteh SE, Aizuddin AN, Tumian NR, Sathar J, Mohamad Selamat E
    PLoS One, 2021;16(8):e0256804.
    PMID: 34449814 DOI: 10.1371/journal.pone.0256804
    Chronic Myeloid Leukaemia (CML) responds well with the targeted therapy drugs, Tyrosine Kinase Inhibitors (TKI), that give potentially long-term disease control for the patients. The objective of this study was to determine the disease burden and factors influencing the health-related quality of life (HRQoL) and health status of CML patients in Klang Valley, Malaysia. CML patients were recruited from haematological outpatient clinics in health centres in Klang Valley, Malaysia. A semi-guided self-administered questionnaire was used. HRQoL was measured by EQ-5D utility value and health status was by visual analogue score (VAS). Logistic regression analysis was conducted to determine the factors influencing HRQoL and health status. A total of 221 respondents participated, where more than half were Malay (56.6%), male (53.4%), and an Imatinib user (68.8%). Majority were diagnosed at the chronic phase (89.5%). The mean age of diagnosis was 41 years old. Significant determinant associated with HRQoL was age of diagnosis. These factors had no significant effect on the HRQoL of these patients regardless of types of TKI used and initial phase of CML. The overall HRQoL of CML patients were comparable to, if not higher, than the general population. Any TKI that was good enough to eliminate disease symptoms and erase patient's worries, can possibly make CML patients have a better quality of life than typical cancer patients and even the general population.
  9. Fulltext Inequality in Drug Utilization among Chronic Myeloid Leukaemia Patients in Malaysia: A Cost-Utility Analysis
    Wan Puteh SE, Mohamad Selamat E, Aizuddin AN, Tumian NR, Sathar J
    Asian Pac J Cancer Prev, 2022 Dec 01;23(12):4253-4260.
    PMID: 36580008 DOI: 10.31557/APJCP.2022.23.12.4253
    BACKGROUND: The burden of chronic myeloid leukaemia (CML) is increasing due to longer patient survival, better life expectancy of the general population, and increasing drug prices. Funding is one of the main concerns in the choice of CML medication used worldwide; thus, patient assistance programmes were introduced to ensure accessibility to affordable treatment. In this study, we evaluated CML drug distribution inequality in Malaysia through patient assistance programmes, using pharmaco-economics methods to evaluate CML treatment from the care provider's perspective.

    METHODS: Patients with CML were recruited from outpatient haematological clinics at the national centre of intervention and referral for haematological conditions and a public teaching hospital. The health-related quality of life or utility scores were derived using the EuroQol EQ-5D-5L questionnaire. Costing data were obtained from the Ministry of Health Malaysia Casemix MalaysianDRG. Imatinib and nilotinib drug costs were obtained from the administration of the participating hospitals and pharmaceutical company.

    RESULTS: Of the 221 respondents in this study, 68.8% were imatinib users. The total care provider cost for CML treatment was USD23,014.40 for imatinib and USD43,442.69 for nilotinib. The governmental financial assistance programme reduced the total care provider cost to USD13,693.51 for imatinib and USD19,193.45 for nilotinib. The quality-adjusted life years (QALYs) were 17.87 and 20.91 per imatinib and nilotinib user, respectively. Nilotinib had a higher drug cost than imatinib, yet its users had better life expectancy, utility score, and QALYs. Imatinib yielded the lowest cost per QALYs at USD766.29.

    CONCLUSION: Overall, imatinib is more cost-effective than nilotinib for treating CML in Malaysia from the care provider's perspective. The findings demonstrate the importance of cancer drug funding assistance for ensuring that the appropriate treatments are accessible and affordable and that patients with cancer use and benefit from such patient assistance programmes. To establish effective health expenditure, drug distribution inequality should be addressed.

  10. Fulltext Genomic Alterations, Gene Expression Profiles and Functional Enrichment of Normal-Karyotype Acute Myeloid Leukaemia Based on Targeted Next-Generation Sequencing
    Ambayya A, Razali R, Sulong S, Zulkefli ES, Yap YY, Sathar J, et al.
    Cancers (Basel), 2023 Feb 22;15(5).
    PMID: 36900179 DOI: 10.3390/cancers15051386
    Characterising genomic variants is paramount in understanding the pathogenesis and heterogeneity of normal-karyotype acute myeloid leukaemia (AML-NK). In this study, clinically significant genomic biomarkers were ascertained using targeted DNA sequencing and RNA sequencing on eight AML-NK patients' samples collected at disease presentation and after complete remission. In silico and Sanger sequencing validations were performed to validate variants of interest, and they were followed by the performance of functional and pathway enrichment analyses for overrepresentation analysis of genes with somatic variants. Somatic variants involving 26 genes were identified and classified as follows: 18/42 (42.9%) as pathogenic, 4/42 (9.5%) as likely pathogenic, 4/42 (9.5%) as variants of unknown significance, 7/42 (16.7%) as likely benign and 9/42 (21.4%) as benign. Nine novel somatic variants were discovered, of which three were likely pathogenic, in the CEBPA gene with significant association with its upregulation. Transcription misregulation in cancer tops the affected pathways involving upstream genes (CEBPA and RUNX1) that were deregulated in most patients during disease presentation and were closely related to the most enriched molecular function gene ontology category, DNA-binding transcription activator activity RNA polymerase II-specific (GO:0001228). In summary, this study elucidated putative variants and their gene expression profiles along with functional and pathway enrichment in AML-NK patients.
  11. Fulltext Clinical and immunological markers of dengue progression in a study cohort from a hyperendemic area in Malaysia
    Rathakrishnan A, Klekamp B, Wang SM, Komarasamy TV, Natkunam SK, Sathar J, et al.
    PLoS One, 2014;9(3):e92021.
    PMID: 24647042 DOI: 10.1371/journal.pone.0092021
    With its elusive pathogenesis, dengue imposes serious healthcare, economic and social burden on endemic countries. This study describes the clinical and immunological parameters of a dengue cohort in a Malaysian city, the first according to the WHO 2009 dengue classification.
  12. Amplification of BCR-ABL and t(3;21) in a patient with blast crisis of chronic myelogenous leukemia
    Phan CL, Megat Baharuddin PJ, Chin LP, Zakaria Z, Yegappan S, Sathar J, et al.
    Cancer Genet. Cytogenet., 2008 Jan 1;180(1):60-4.
    PMID: 18068536
    The Philadelphia (Ph) chromosome, or t(9;22), is the hallmark of chronic myelogenous leukemia (CML). It results in juxtaposition of the 5' part of the BCR gene on chromosome 22 to the 3' part of the ABL1 gene (previously ABL) on chromosome 9. CML is clinically characterized by three distinct phases: chronic, accelerated, and blast phase. Blast crisis is characterized by the rapid expansion of a population of differentiation arrested blast cells (myeloid or lymphoid cells population), with secondary chromosomal abnormalities present. We report a case of myeloid blast crisis of CML resistant to imatinib mesylate and chemotherapy. By use of cytogenetic, fluorescence in situ hybridization, and comparative genomic hybridization methods, we identified a cluster of BCR-ABL amplification on inverted duplication of the Ph chromosome with t(3;21)(q26;q22) and increased genomic levels of the RUNX1 gene (previously AML1). The t(3;21)(q26;q22) is a recurrent chromosomal abnormality in some cases of CML blast phase and in treatment-related myelodysplastic syndrome and acute myeloid leukemia. Amplification or copy number increase of RUNX1 has been reported in childhood acute lymphoblastic leukemia. Our study indicated that the progenitor of CML was BCR-ABL dependent through the amplification of Ph chromosome as a mechanism of resistance to imatinib therapy. The coexistence of BCR-ABL and t(3;21)(q26;q22) with RUNX1 rearrangement might play a pivotal role in the CML blast transformation.
  13. Fulltext Dengue patients exhibit higher levels of PrM and E antibodies than their asymptomatic counterparts
    Yeo AS, Rathakrishnan A, Wang SM, Ponnampalavanar S, Manikam R, Sathar J, et al.
    Biomed Res Int, 2015;2015:420867.
    PMID: 25815314 DOI: 10.1155/2015/420867
    Dengue virus infection is a common tropical disease which often occurs without being detected. These asymptomatic cases provide information in relation to the manifestation of immunological aspects. In this study, we developed an ELISA method to compare neutralizing effects of dengue prM and E antibodies between dengue patients and their asymptomatic household members. Recombinant D2 premembrane (prM) was constructed, cloned, and tested for antigenicity. The recombinant protein was purified and tested with controls by using an indirect ELISA method. Positive dengue serum samples with their asymptomatic pair were then carried out onto the developed ELISA. In addition, commercially available recombinant envelope (E) protein was used to develop an ELISA which was tested with the same set of serum samples in the prM ELISA. Asymptomatic individuals showed preexisting heterotypic neutralizing antibodies. The recombinant prM was antigenically reactive in the developed ELISA. Dengue patients had higher prM and E antibodies compared to their household members. Our study highlights the neutralizing antibodies levels with respect to dengue prM and E between dengue patients and asymptomatic individuals.
  14. Importance of extended blood group genotyping in multiply transfused patients
    Osman NH, Sathar J, Leong CF, Zulkifli NF, Raja Sabudin RZA, Othman A, et al.
    Transfus Apher Sci, 2017 Jun;56(3):410-416.
    PMID: 28438419 DOI: 10.1016/j.transci.2017.03.009
    Blood group antigen systems are not limited to the ABO blood groups. There is increasing interest in the detection of extended blood group systems on the red cell surface. The conventional method used to determine extended blood group antigens or red cell phenotype is by serological testing, which is based on the detection of visible haemagglutination or the presence of haemolysis. However, this technique has many limitations due to recent exposure to donor red cell, certain drugs or medications or other diseases that may alter the red cell membrane. We aimed to determine the red cell blood group genotype by SNP real time PCR and to compare the results with the conventional serological methods in multiply transfused patients. Sixty-three patients participated in this study whose peripheral blood was collected and blood group phenotype was determined by serological tube method while the genotype was performed using TaqMan®Single Nucleotide Polymorphism (SNP) RT-PCR assays for RHEe, RHCc, Kidd and Duffy blood group systems. Discrepancies were found between the phenotype and genotype results for all blood groups tested. Accurate red blood cell antigen profiling is important for patients requiring multiple transfusions. The SNP RT-PCR platform is a reliable alternative to the conventional method.
  15. Fulltext Aberrant monocyte responses predict and characterize dengue virus infection in individuals with severe disease
    Yong YK, Tan HY, Jen SH, Shankar EM, Natkunam SK, Sathar J, et al.
    J Transl Med, 2017 05 31;15(1):121.
    PMID: 28569153 DOI: 10.1186/s12967-017-1226-4
    BACKGROUND: Currently, several assays can diagnose acute dengue infection. However, none of these assays can predict the severity of the disease. Biomarkers that predicts the likelihood that a dengue patient will develop a severe form of the disease could permit more efficient patient triage and allows better supportive care for the individual in need, especially during dengue outbreaks.

    METHODS: We measured 20 plasma markers i.e. IFN-γ, IL-10, granzyme-B, CX3CL1, IP-10, RANTES, CXCL8, CXCL6, VCAM, ICAM, VEGF, HGF, sCD25, IL-18, LBP, sCD14, sCD163, MIF, MCP-1 and MIP-1β in 141 dengue patients in over 230 specimens and correlate the levels of these plasma markers with the development of dengue without warning signs (DWS-), dengue with warning signs (DWS+) and severe dengue (SD).

    RESULTS: Our results show that the elevation of plasma levels of IL-18 at both febrile and defervescence phase was significantly associated with DWS+ and SD; whilst increase of sCD14 and LBP at febrile phase were associated with severity of dengue disease. By using receiver operating characteristic (ROC) analysis, the IL-18, LBP and sCD14 were significantly predicted the development of more severe form of dengue disease (DWS+/SD) (AUC = 0.768, P 

  16. Fulltext Turoctocog alfa pegol provides effective management for major and minor surgical procedures in patients across all age groups with severe haemophilia A: Full data set from the pathfinder 3 and 5 phase III trials
    Tosetto A, Neff A, Lentz SR, Santagostino E, Nemes L, Sathar J, et al.
    Haemophilia, 2020 May;26(3):450-458.
    PMID: 32293786 DOI: 10.1111/hae.13980
    INTRODUCTION: Turoctocog alfa pegol is a glycoPEGylated recombinant factor VIII (FVIII) with an extended half-life developed for prophylaxis, treatment of bleeds and perioperative management in patients with haemophilia A.

    AIM: Evaluate the efficacy and safety of turoctocog alfa pegol treatment for major and minor surgeries in the pathfinder 3 and 5 phase III trials.

    METHODS: Adults/adolescents aged ≥12 years with severe haemophilia A (FVIII <1%) received perioperative turoctocog alfa pegol treatment planned to achieve FVIII activity levels >80% during major surgery (pathfinder 3). The primary end point was haemostatic efficacy during surgery; secondary end points were blood loss, haemostatic effect postsurgery, consumption, transfusions, safety and health economics. Children (0-11 years) undergoing minor surgeries received 20-75 IU/kg turoctocog alfa pegol at Investigator's discretion (pathfinder 5).

    RESULTS: pathfinder 3 included 35 patients undergoing 49 major surgeries. Haemostasis was successful in 47/49 (95.9%) surgeries; two had moderate haemostatic responses. Median (mean) blood loss during major surgery was 75 (322.6) mL. Four bleeds were reported postsurgery; three were successfully treated with turoctocog alfa pegol (one was not evaluated). On the day of surgery, overall mean (median) dose was 75.5 (74.5) IU/kg and mean (median) number of doses was 1.7 (2.0). Five procedures required 11 transfusions on the day of surgery or days 1-6. No safety concerns or inhibitors were identified. Forty-five minor surgeries in 23 children were performed without complications.

    CONCLUSION: Turoctocog alfa pegol was effective for perioperative haemostatic management of major and minor surgeries in patients across age groups with severe haemophilia A.

  17. Clinical and haematological characteristics of 38 individuals with Hb G-Makassar in Malaysia
    Esa E, Mohamad AS, Hamzah R, Hamid FSA, Aziz NA, Sevaratnam V, et al.
    EJHaem, 2023 Nov;4(4):940-948.
    PMID: 38024609 DOI: 10.1002/jha2.750
    Haemoglobin (Hb) G-Makassar is a rare Hb variant. It presents a diagnostic challenge as it imitates sickle Hb (Hb S) in standard electrophoresis and high-performance liquid chromatography assays requiring DNA analysis to confirm diagnosis. Both have point mutations in codon 6, exon 1 in the β-globin (HBB) gene with different pathogenicities. This study describes the clinical phenotype, haematology and genotype of Hb G-Makassar. Clinical and laboratory data of 38 cases of Hb G-Makassar over 8 years were analysed. Hb G-Makassar was confirmed by a direct sequencing of HBB gene and co-inheritance of α-thalassaemia determined through multiplex gap-PCR and multiplex Amplification Refractory Mutation System polymerase chain reaction. All cases were Malays, predominantly from Terengganu (n = 20, 52.6%). There were 14 (36.8%) males and 24 (63.2%) females with median age of 25 years. Majority (n = 33, 86.8%) had features of thalassaemia trait with mean ± SD for Hb, mean cell volume (MCV) and mean cell haemoglobin (MCH) as 13.21 g/dL ± 1.69, 73.06 ± 4.48 fL and 24.71 ± 1.82 pg, respectively. None had evidence of haemolysis or thromboembolic complications. Six genotypes were identified; ßG-Makassar/ß,αα/αα (n = 19, 50.0%), ßG-Makassar/ßE,αα/αα (n = 4, 10.5%), ßG-Makassar/ßNewYork,αα/αα (n = 1, 2.6%), ßG-Makassar/ß,αα/-α (n = 11, 28.9%), ßG-Makassar/ß,αα/αAdanaα (n = 2, 5.3%) and ßG-Makassar/ß,αα/-SEA (n = 1, 2.6%). The ßG-Makassar/ß,αα/αα showed that features of thalassaemia trait with mean ± SD for Hb, MCV and MCH were 13.74 g/dL ± 2.40, 76.18 ± 6.02 fL and 25.79 ± 2.41 pg, respectively. This is the largest study reporting a significant number of Hb G-Makassar in Malaysia. Although the mutation is similar to Hb S, the phenotype is benign.
  18. Fulltext Haematological reference intervals in a multiethnic population
    Ambayya A, Su AT, Osman NH, Nik-Samsudin NR, Khalid K, Chang KM, et al.
    PLoS One, 2014;9(3):e91968.
    PMID: 24642526 DOI: 10.1371/journal.pone.0091968
    INTRODUCTION: Similar to other populations, full blood count reference (FBC) intervals in Malaysia are generally derived from non-Malaysian subjects. However, numerous studies have shown significant differences between and within populations supporting the need for population specific intervals.

    METHODS: Two thousand seven hundred twenty five apparently healthy adults comprising all ages, both genders and three principal races were recruited through voluntary participation. FBC was performed on two analysers, Sysmex XE-5000 and Unicel DxH 800, in addition to blood smears and haemoglobin analysis. Serum ferritin, soluble transferrin receptor and C-reactive protein assays were performed in selected subjects. All parameters of qualified subjects were tested for normality followed by determination of reference intervals, measures of central tendency and dispersion along with point estimates for each subgroup.

    RESULTS: Complete data was available in 2440 subjects of whom 56% (907 women and 469 men) were included in reference interval calculation. Compared to other populations there were significant differences for haemoglobin, red blood cell count, platelet count and haematocrit in Malaysians. There were differences between men and women, and between younger and older men; unlike in other populations, haemoglobin was similar in younger and older women. However ethnicity and smoking had little impact. 70% of anemia in premenopausal women, 24% in postmenopausal women and 20% of males is attributable to iron deficiency. There was excellent correlation between Sysmex XE-5000 and Unicel DxH 800.

    CONCLUSION: Our data confirms the importance of population specific haematological parameters and supports the need for local guidelines rather than adoption of generalised reference intervals and cut-offs.

  19. Fulltext Autologous stem cell transplantation (ASCT) outcome for multiple myeloma in a tertiary referral centre in Malaysia
    Liam CCK, Boo YL, Lee YL, Law KB, Ho KW, Shahnaz SAKS, et al.
    Blood Cell Ther, 2021 Feb 25;4(1):1-8.
    PMID: 36712843 DOI: 10.31547/bct-2020-009
    BACKGROUND: Multiple Myeloma (MM) is characterized by the presence of clonal plasma cells. These often result in complications including bone destruction, hypercalcemia, renal insufficiency, and anaemia. Induction with a triplet or quadruplet regimen followed by autologous stem cell transplantation (ASCT) has been the standard of care for transplant eligible patients to achieve durable remission.

    PURPOSE: This is a retrospective analytical study to determine the outcome of Multiple Myeloma patients who underwent ASCT in Ampang Hospital.

    MATERIALS AND METHODS: We included a 5-year cohort of patients transplanted from 1st July 2014 to 30th June 2019. Data were obtained through electronic medical records. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were analyzed using simple and multiple Cox proportional hazard regression analysis. All analyses were done using software R version 3.6.2 with validated statistical packages.

    RESULTS: 139 patients were analyzed. The median age at transplant was 56 years old and 56.1% are males (n＝78). The most common subtype is IgG Kappa (n＝67, 48.2%). Only 93 patients in which the International Staging System (ISS) could be determined, and among them, 33.3% of patients (n＝31) have advanced stage Ⅲ disease. The most common induction received before ASCT was a bortezomib based regimen and/or an immunomodulatory (IMiD) based regimen. 63.3% of patients achieved at least a very good partial response (VGPR) before ASCT. Most patients received myeloablative conditioning (MAC) (n＝119, 85.6%). The mean cell dose is 3.68×106/kg. The median time to engraftment was 11 days for both platelet and absolute neutrophil count (ANC). With the median follow-up of 17.3 (range, 6.2-33.4) months, the median OS and PFS were not reached. The 1-year and 2-year PFS were 75% (95% CI 66-82%) and 52% (95% CI 42-62%), respectively. The 1-year and 2-year OS were 82% (95% CI 74-88%) and 70% (95% CI 60-78%), respectively. 6 patients (4.3%) had transplant-related mortality (TRM). IgA subtype was found to adversely affect PFS. Maintenance therapy and the absence of renal impairment was associated with better PFS and OS.

    DISCUSSION AND CONCLUSIONS: Our study found that ASCT following induction treatment is safe and beneficial to achieve a deeper remission status. In our study, the addition of maintenance therapy is associated with an improved outcome in PFS and OS.

  20. Efficacy and safety of fitusiran prophylaxis in people with haemophilia A or haemophilia B with inhibitors (ATLAS-INH): a multicentre, open-label, randomised phase 3 trial
    Young G, Srivastava A, Kavakli K, Ross C, Sathar J, You CW, et al.
    Lancet, 2023 Mar 29.
    PMID: 37003287 DOI: 10.1016/S0140-6736(23)00284-2
    BACKGROUND: Fitusiran, a subcutaneous investigational small interfering RNA therapeutic, targets antithrombin to rebalance haemostasis in people with haemophilia A or haemophilia B, irrespective of inhibitor status. We evaluated the efficacy and safety of fitusiran prophylaxis in people with haemophilia A or haemophilia B with inhibitors.

    METHODS: This multicentre, randomised, open-label phase 3 study was done at 26 sites (primarily secondary or tertiary centres) in 12 countries. Men, boys, and young adults aged 12 years or older with severe haemophilia A or haemophilia B with inhibitors previously treated with on-demand bypassing agents were randomly assigned (2:1) to receive once-a-month 80 mg subcutaneous fitusiran prophylaxis (fitusiran prophylaxis group) or to continue with bypassing agents on-demand (bypassing agents on-demand group) for 9 months. The primary endpoint was mean annualised bleeding rate during the efficacy period in the intention-to-treat population estimated by negative binomial model. Safety was assessed as a secondary endpoint in the safety population. This trial is complete and is registered with ClinicalTrials.gov, NCT03417102.

    FINDINGS: Between Feb 14, 2018, and June 23, 2021, 85 participants were screened for inclusion, of whom 57 (67%; 57 [100%] men; median age 27·0 years [IQR 19·5-33·5]) were randomly assigned: 19 (33%) participants to the bypassing agent on-demand group and 38 (67%) participants to the fitusiran prophylaxis. Negative binomial model-based mean annualised bleeding rate was significantly lower in the fitusiran prophylaxis group (1·7 [95% CI 1·0-2·7]) than in the bypassing agents on-demand group (18·1 [10·6-30·8]), corresponding to a 90·8% (95% CI 80·8-95·6) reduction in annualised bleeding rate in favour of fitusiran prophylaxis (p<0·0001). 25 (66%) participants had zero treated bleeds in the fitusiran prophylaxis group versus one (5%) in the bypassing agents on-demand group. The most frequent treatment-emergent adverse event in the fitusiran prophylaxis group was increased alanine aminotransferase in 13 (32%) of 41 participants in the safety population; there were no increased alanine aminotransferase treatment-emergent adverse events in the bypassing agents on-demand group. Suspected or confirmed thromboembolic events were reported in two (5%) participants in the fitusiran prophylaxis group. No deaths were reported.

    INTERPRETATION: Subcutaneous fitusiran prophylaxis resulted in statistically significant reductions in annualised bleeding rate in participants with haemophilia A or haemophilia B with inhibitors, with two-thirds of participants having zero bleeds. Fitusiran prophylaxis might show haemostatic efficacy in participants with haemophilia A or haemophilia B with inhibitors; therefore, the therapeutic might have the potential to improve the management of people with haemophilia.

    FUNDING: Sanofi.

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