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  1. Ong TC
    J Sports Sci, 1993 Feb;11(1):71-6.
    PMID: 8450589 DOI: 10.1080/02640419308729966
    The maximum oxygen consumption (VO2 max) of 421 healthy adult males from three ethnic groups (Chinese, Malay and Indian), aged 25-54 years, was assessed from direct analyses of their expired respiratory gases during all-out runs on a treadmill as a measure of aerobic fitness. The subjects were divided into three age groups: group 1, 25-34 years; group 2, 35-44 years; group 3, 45-54 years. Each group was further subdivided into non-exercisers (NE), non-regular exercisers (NRE) and regular exercisers (RE). Consistently within each age group, regular exercisers produced significantly higher VO2 max values compared to non-regular exercisers and non-exercisers. They also met the VO2 max requirements for heavy physical work and compared favourably with the standards of the National Physical Fitness Award of Singapore and Cooper's aerobic fitness classification standards based on North American males. Non-regular exercisers and non-exercisers only met the VO2 max requirements for moderate physical work and compared poorly in both of the aerobic fitness standards.
  2. Phan, CL, Ong, TC, Chang, KM, Zubaidah, Z., Puteri Jamilatul, N.M.B.
    Medicine & Health, 2010;5(1):45-48.
    MyJurnal
    The t(8;21)(q22;q22) is a frequently occurring aberration in acute myeloid leukemia (AML) (18-20%) and usually correlate with French-America-British (FAB) M2 subtype. Several studies showed that patients carrying this abnormality demonstrated good response to standard chemotherapy but also have a high incidence of disease relapse. Trisomy 4 is a rare and specific chromosomal abnormality occurring in AML M2 or M4 of the FAB subtypes. We report a case of a 33-year-old female with an apparently clinical and hematologic diagnosis of acute promyelocytic leukemia (APL) in whom cytogenetic analysis revealed an abnormal karyotype with trisomy 4, in addition to t(8;21). Trisomy 4 and t(8;21) in a patient with AML is rare. The significance of t(8;21) with trisomy 4 in AML are unclear but patients bearing this abnormality are associated with a poor prognosis.
  3. Chang KM, Ong TC
    Med J Malaysia, 2008 Sep;63 Suppl C:66-7.
    PMID: 19227675
    Treatment option of Haematological malignancies has expanded over the last decade. The outcome of treatment is expected to be better compare to previously. However, study of treatment outcome for haematological malignancies has not been carried out in Malaysia. The goal of this study is to measure the treatment outcome in patients with haematological malignancy.
  4. Wan Jamaludin WF, Kok WH, Loong L, Palaniappan SK, Zakaria MZ, Ong TC, et al.
    Med J Malaysia, 2018 12;73(6):430-432.
    PMID: 30647224
    Immune Thrombocytopenia Purpura (ITP) secondary to vaccinations is rare, especially after autologous hematopoietic stem cell transplantation (HSCT). A 31-yearold female received autologous HSCT for relapsed Hodgkin Disease, with platelet engraftment at Day+14. One week after receiving second scheduled vaccinations, she developed severe thrombocytopenia (3x109/L) associated with pharyngeal hematoma. Bone marrow (BM) examinations were consistent with ITP, possibly secondary to Influenza vaccine. Platelet increment was poor despite high dose corticosteroids, intravenous immunoglobulin (IVIG), Danazol and Eltrombopag. A repeated BM biopsy was in agreement with ITP. Re-treatment with tapering doses of prednisolone resulted in stable platelet counts at 120x109/L a year later.
  5. Law KB, Chang KM, Hamzah NA, Ng KH, Ong TC
    Indian J Hematol Blood Transfus, 2017 Dec;33(4):483-491.
    PMID: 29075058 DOI: 10.1007/s12288-017-0790-3
    The study aimed to investigate the effect of consolidation treatment with fludarabine, high-dose cytarabine and granulocyte colony-stimulating factor or FLAG in older AML patients. The study included 41 eligible patients above 54 years old, who received both induction and consolidation chemotherapy for AML from 2008 to 2013. The study cohort had a minimum 24 months follow-up period. Survival analysis was carried out to assess patients' overall survival and disease free survival based on types of consolidation regimens. The consolidation treatment with FLAG exerted a protective effect to both overall survival and disease free survival in older patients. Patients who were consolidated with FLAG regimen had a significant longer overall survival (log-rank, p = 0.0025) and disease free survival (log-rank, p = 0.0026). The median overall survival was longer (18.70 months) with the use of FLAG when compared to non-FLAG group (8.09 months). The median disease free survival was also longer (13.84 months) with use of FLAG when compared to the non-FLAG group (4.44 months). Regression analysis with Cox model yielded hazard ratio of 0.245 (p = 0.0094) in overall survival and 0.217 (p = 0.0068) in disease free survival. The use of FLAG as consolidation treatment was associated with approximately 60-80% reduction in hazard rates. The result was adjusted for age, race and gender in regression analysis. Older AML patients had longer remission and survival when consolidated with FLAG regimen after the induction chemotherapy.
  6. Wilfred G, Ong TC, Sh Shahnaz SAK, Wah HK, Carlo ES, Jameela S, et al.
    Blood Cell Ther, 2022 May 25;5(2):45-53.
    PMID: 36710947 DOI: 10.31547/bct-2021-018
    BACKGROUND: Hematopoietic stem cell transplantation (HSCT) provides curative therapy in almost 90% of patients with severe aplastic anemia (SAA). Older age, long duration of disease with consequent heavy exposure to transfusion, and active infection at the time of HSCT have a negative influence on the outcomes, causing graft failure (GF) and graft versus host disease (GVHD).

    PURPOSE: To describe the outcomes of all patients with SAA who received hematopoietic stem cell transplantation at a tertiary center in Malaysia.

    MATERIALS AND METHODS: We included a 20 y cohort of patients who underwent transplantation from January 1, 1999 to December 31, 2019. Data were obtained from electronic medical records. Demographics, clinical characteristics, and treatment outcomes were analyzed using descriptive statistics. Overall survival (OS) was analyzed using Kaplan-Meier curves. All analyses were conducted using the Statistical Package for the Social Sciences (SPSS) version 25.

    RESULTS: Eighty patients were analyzed. The median age at diagnosis was 19 years, and 59% patients were male (n = 47). Malay ethnicity was the highest (52.5%), followed by Chinese (20.0%) and Native Sabah (15.0%). The median duration from diagnosis to transplantation was 13.5 weeks. A majority of patients received Cy-ATG conditioning (n = 51, 63.8%). Forty-one patients (51.2%) used peripheral blood as stem cell source, 36 patients (45.0%) used granulocyte colony stimulating factor (G-CSF) primed marrow graft and 3 patients (3.8%) used both. The mean nucleated mononuclear cell and CD34 cell doses were 4.7 ± 1.7 × 108/kg and 4.6 ± 1.9 × 106/kg, respectively. Median engraftment for WBCs and platelets was 14 and 15 days, respectively. There was no difference in WBC and platelet engraftment in patients who received peripheral blood stem cell transplantation or bone marrow transplant. At a median follow-up of 54 months, 49 patients (61.3%) achieved complete remission and 8 patients (10.0%) achieved partial remission. The estimated 5 y OS was 63% and higher among those who received HSCT within 3 months of diagnosis. Twenty-two patients (27.5%) died within 100 d of transplantation, and a majority of these died due to pre-engraftment death.

    DISCUSSION AND CONCLUSIONS: Our study found that patients who received early allogeneic transplantation for SAA had better outcomes. Pre-engraftment failure was the major cause of transplant-related mortality within 100 d. Further studies are required to identify the factors responsible for delaying transplantation to improve treatment outcomes.

  7. Chong SL, Ahmad Asnawi AW, Hamzah R, Liew PK, Ong TC, Tan SM, et al.
    Case Rep Oncol, 2021;14(3):1814-1820.
    PMID: 35111014 DOI: 10.1159/000521159
    Cancer-related microangiopathic hemolytic anemia (MAHA) is a rare and life-threatening condition. We present a patient who had been treated for invasive lobular breast carcinoma in clinical remission with fever and hemolytic anemia. The peripheral blood film showed MAHA and thrombocytopenia, and a functional deficiency of ADAMTS13 activity of 23% consistent with acquired thrombotic thrombocytopenic purpura. Bone marrow aspirate and trephine biopsy confirmed metastatic carcinoma. Further evaluation revealed the involvement of multiple bone sites without recurrence of the primary tumor. The patient received a daily plasma exchange with cryosupernatant and was pulsed with corticosteroids. MAHA related to breast cancer appears to be a rare occurrence.
  8. Suthandiram S, Gan GG, Mohd Zain S, Bee PC, Lian LH, Chang KM, et al.
    Tumour Biol., 2015 Mar;36(3):1819-34.
    PMID: 25384508 DOI: 10.1007/s13277-014-2785-0
    Corroborating evidence related to the role of aberrations on one-carbon metabolism (OCM) genes has been inconsistent. We evaluated the association between polymorphisms in 12 single nucleotide polymorphisms (SNPs) in 8 OCM genes (CBS, FPGS, FTHFD, MTRR, SHMT1, SLC19A1, TCN1, and TYMS), and non-Hodgkin lymphoma (NHL) risk in a multi-ethnic population which includes Malay, Chinese and Indian ethnic subgroups. Cases (N = 372) and controls (N = 722) were genotyped using the Sequenom MassARRAY platform. Our results of the pooled subjects showed a significantly enhanced NHL risk for CBS Ex9 + 33C > T (T versus C: OR 1.55, 95% CI 1.22-1.96, P = 0.0003), CBS Ex18-319G > A (A versus G: OR 1.15, 95% CI 1.14-1.83; P = 0.002), SHMT1 Ex12 + 236 T > C (T versus C: OR 1.44, 95% CI 1.15-1.81, P = 0.002), and TYMS Ex8 + 157C > T (T versus C: OR 1.29, 95% CI 1.06-1.57, P = 0.01). Haplotype analysis for CBS SNPs showed a significantly decreased risk of NHL in subjects with haplotype CG (OR 0.69, 95% CI 0.56-0.86, P = <0.001). The GG haplotype for the FTHFD SNPs showed a significant increased risk of NHL (OR 1.40, 95% CI 1.12-1.76, P = 0.002). For the TYMS gene, haplotype CAT at TYMS (OR 0.67, 95% CI 0.49-0.90, P = 0.007) was associated with decreased risk of NHL, while haplotype TAC (OR 1.29, 95% CI 1.05-1.58, P = 0.01) was found to confer increased risk of NHL. Our study suggests that variation in several OCM genes (CBS, FTHFD, SHMT1, TCN1, and TYMS) may influence susceptibility to NHL.
  9. Suthandiram S, Gan GG, Zain SM, Bee PC, Lian LH, Chang KM, et al.
    Pharmacogenomics, 2014 Aug;15(11):1479-94.
    PMID: 25303299 DOI: 10.2217/pgs.14.97
    Pharmacogenetics of methotrexate (MTX) contributes to interindividual differences in toxicity. We aimed to evaluate the impact of SNPs within the MTX pathway genes on MTX-induced toxicity and MTX plasma levels at 48 h following treatment in Asian adults with acute lymphoblastic leukemia or non-Hodgkin lymphoma.
  10. Suthandiram S, Gan GG, Zain SM, Haerian BS, Bee PC, Lian LH, et al.
    J Hum Genet, 2014 May;59(5):280-7.
    PMID: 24646728 DOI: 10.1038/jhg.2014.19
    An imbalance in folate metabolism can adversely affect DNA synthesis and methylation systems which can lead to susceptibility to non-Hodgkin lymphoma (NHL). Whether single nucleotide polymorphisms (SNPs) and their haplotypes in the methylenetetrahydrofolate reductase (MTHFR) are associated with NHL, remain inconclusive. We investigated the association between MTHFR C677T and A1298C SNPs and NHL risk in a population which is made up of Malay, Chinese and Indian ethnic subgroups. A total of 372 NHL patients and 722 controls were genotyped using the Sequenom MassARRAY platform. Our results of the pooled subjects failed to demonstrate significant association between the MTHFR C677T and A1298C SNPs with NHL and its subtypes. The results were in agreement with the previous meta-analyses. In the Indian ethnic subgroup however, single locus analysis of MTHFR A1298C appears to confer risk to NHL (Odds ratio (OR) 1.91, 95% confidence interval (95% CI) 1.22-3.00, P=0.006). The risk is almost doubled in homozygous carrier of MTHFR 1298CC (OR 4.03, 95% CI 1.56-10.43, P=0.004). Haplotype analysis revealed higher frequency of CC in the Indian NHL patients compared with controls (OR 1.86, 95% CI 1.18-2.93, P=0.007). There is lack of evidence to suggest an association between MTHFR C677T and A1298C with the risk of NHL in the Malays and Chinese. In the Indians however, the MTHFR A1298C confers risk to NHL. This study suggests ethnicity modifies the relationship between polymorphisms in the folate-metabolizing gene and NHL.
  11. Lim YY, Chin YM, Tai MC, Fani S, Chang KM, Ong TC, et al.
    Leuk Lymphoma, 2015 Jan;56(1):163-8.
    PMID: 24684230 DOI: 10.3109/10428194.2014.907895
    We evaluated the association of two IL10 single nucleotide polymorphisms (SNPs) (rs1800896 and rs1800871) with non-Hodgkin lymphoma (NHL) risk in the three major races of the Malaysian population (Malay, Chinese and Indian; 317 cases and 330 controls). Our initial screening demonstrated that rs1800871 but not rs1800896 was significantly associated with increased NHL risk in Malays (pMalay-Rec = 0.007) and Chinese only (pChinese-Rec = 0.039). Subsequent combined analysis of the Malay and Chinese revealed significant association of rs1800871 with all (ALL) NHL subtypes (pMeta-ALL-NHL-Rec = 0.001), ALL B-cell subtypes (pMeta-ALL-B-cell-Rec = 0.003), diffuse large B-cell lymphoma (DLBCL) subtype (pMeta-DLBCL-Rec = 0.002) and ALL T-cell subtypes (pMeta-ALL-T-cell-Rec = 0.031). SNP rs1800896 showed increased risk only in follicular lymphoma (FL) (pMeta-FL-Dom = 0.0004). We also detected a male-specific association of rs1800871 with increased NHL risk (pMeta-Male-ALL-NHL-Rec = 0.006) in the combined analysis. To our knowledge, this is the first report on the association of IL10 promoter SNPs with NHL susceptibility in the three major races of Malaysia.
  12. Chan SL, Ong TC, Gao YF, Tiong YS, Wang de Y, Chew FT, et al.
    J Immunol, 2008 Aug 15;181(4):2586-96.
    PMID: 18684949
    A high incidence of sensitization to Blomia tropicalis, the predominant house dust mite species in tropical regions, is strongly associated with allergic diseases in Singapore, Malaysia, and Brazil. IgE binding to the group 5 allergen, Blo t 5, is found to be the most prevalent among all B. tropicalis allergens. The NMR structure of Blo t 5 determined represents a novel helical bundle structure consisting of three antiparallel alpha-helices. Based on the structure and sequence alignment with other known group 5 dust mite allergens, surface-exposed charged residues have been identified for site-directed mutagenesis and IgE binding assays. Four charged residues, Glu76, Asp81, Glu86, and Glu91 at around the turn region connecting helices alpha2 and alpha3 have been identified to be involved in the IgE binding. Using overlapping peptides, we have confirmed that these charged residues are located on a major putative linear IgE epitope of Blo t 5 from residues 76-91 comprising the sequence ELKRTDLNILERFNYE. Triple and quadruple mutants have been generated and found to exhibit significantly lower IgE binding and reduced responses in skin prick tests. The mutants induced similar PBMC proliferation as the wild-type protein but with reduced Th2:Th1 cytokines ratio. Mass screening on a quadruple mutant showed a 40% reduction in IgE binding in 35 of 42 sera of atopic individuals. Findings in this study further stressed the importance of surface-charged residues on IgE binding and have implications in the cross-reactivity and use of Blo t 5 mutants as a hypoallergen for immunotherapy.
  13. Ten LC, Chin YM, Tai MC, Chin EF, Lim YY, Suthandiram S, et al.
    Sci Rep, 2017 01 31;7:41400.
    PMID: 28139690 DOI: 10.1038/srep41400
    Large consortia efforts and genome-wide association studies (GWASs) have linked a number of genetic variants within the 6p21 chromosomal region to non-Hodgkin lymphoma (NHL). Complementing these efforts, we genotyped previously reported SNPs in the human leukocyte antigen (HLA) class I (rs6457327) and class II (rs9271100, rs2647012 and rs10484561) regions in a total of 1,145 subjects (567 NHL cases and 578 healthy controls) from two major ethnic groups in Malaysia, the Malays and the Chinese. We identified a NHL-associated (PNHL_add = 0.0008; ORNHL_add = 0.54; 95% CI = 0.37-0.77) and B-cell associated (PBcell_add = 0.0007; ORBcell_add = 0.51; 95% CI = 0.35-0.76) SNP rs2647012 in the Malaysian Malays. In silico cis-eQTL analysis of rs2647012 suggests potential regulatory function of nearby HLA class II molecules. Minor allele rs2647012-T is linked to higher expression of HLA-DQB1, rendering a protective effect to NHL risk. Our findings suggest that the HLA class II region plays an important role in NHL etiology.
  14. 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.

  15. 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.
  16. 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.
  17. Hughes TP, Munhoz E, Aurelio Salvino M, Ong TC, Elhaddad A, Shortt J, et al.
    Br J Haematol, 2017 10;179(2):219-228.
    PMID: 28699641 DOI: 10.1111/bjh.14829
    The Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Extending Molecular Responses (ENESTxtnd) study was conducted to evaluate the kinetics of molecular response to nilotinib in patients with newly diagnosed chronic myeloid leukaemia in chronic phase and the impact of novel dose-optimization strategies on patient outcomes. The ENESTxtnd protocol allowed nilotinib dose escalation (from 300 to 400 mg twice daily) in the case of suboptimal response or treatment failure as well as dose re-escalation for patients with nilotinib dose reductions due to adverse events. Among 421 patients enrolled in ENESTxtnd, 70·8% (95% confidence interval, 66·2-75·1%) achieved major molecular response (BCR-ABL1 ≤ 0·1% on the International Scale) by 12 months (primary endpoint). By 24 months, 81·0% of patients achieved major molecular response, including 63·6% (56 of 88) of those with dose escalations for lack of efficacy and 74·3% (55 of 74) of those with dose reductions due to adverse events (including 43 of 54 patients with successful re-escalation). The safety profile of nilotinib was consistent with prior studies. The most common non-haematological adverse events were headache, rash, and nausea; cardiovascular events were reported in 4·5% of patients (grade 3/4, 3·1%). The study was registered at clinicaltrials.gov (NCT01254188).
  18. Yap YY, Law KB, Sathar J, Lau NS, Goh AS, Chew TK, et al.
    Exp Hematol Oncol, 2018;7:31.
    PMID: 30564475 DOI: 10.1186/s40164-018-0124-7
    Background: The evolution of molecular studies in myeloproliferative neoplasms (MPN) has enlightened us the understanding of this complex disease consisting of polycythaemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The epidemiology is well described in the western world but not in Asian countries like Malaysia.

    Materials and methods: This retrospective national registry of MPN was conducted from year 2009 to 2015 in Malaysia.

    Results: A total of 1010 patients were registered over a period of 5 years. The mean age was 54 years with male predominance. The ethnic distribution revealed that Chinese had a relatively high weighted incidence proportion (43.2%), followed by Indian (23.8%), Malay (15.8%) and other ethnic groups (17.2%). The types of MPN reported were 40.4% of ET (n = 408), 38.1% of PV (n = 385), 9.2% of PMF (n = 93), 3.1% of hypereosinophilic syndrome (HES) (n = 31) and 7.9% of unclassifiable MPN (MPN-U) (n = 80). Splenomegaly was only palpable clinically in 32.2% of patients. The positive JAK2 V617F mutation was present in 644 patients with 46.6% in PV, 36.0% in ET, 9.0% in PMF, and 7.4% in MPN-U, and had significantly lower haemoglobin (p 

  19. Mac Aogáin M, Tiew PY, Lim AYH, Low TB, Tan GL, Hassan T, et al.
    Am J Respir Crit Care Med, 2019 04 01;199(7):842-853.
    PMID: 30265843 DOI: 10.1164/rccm.201807-1355OC
    RATIONALE: Allergic sensitization is associated with poor clinical outcomes in asthma, chronic obstructive pulmonary disease, and cystic fibrosis; however, its presence, frequency, and clinical significance in non-cystic fibrosis bronchiectasis remain unclear.

    OBJECTIVES: To determine the frequency and geographic variability that exists in a sensitization pattern to common and specific allergens, including house dust mite and fungi, and to correlate such patterns to airway immune-inflammatory status and clinical outcomes in bronchiectasis.

    METHODS: Patients with bronchiectasis were recruited in Asia (Singapore and Malaysia) and the United Kingdom (Scotland) (n = 238), forming the Cohort of Asian and Matched European Bronchiectasis, which matched recruited patients on age, sex, and bronchiectasis severity. Specific IgE response against a range of common allergens was determined, combined with airway immune-inflammatory status and correlated to clinical outcomes. Clinically relevant patient clusters, based on sensitization pattern and airway immune profiles ("immunoallertypes"), were determined.

    MEASUREMENTS AND MAIN RESULTS: A high frequency of sensitization to multiple allergens was detected in bronchiectasis, exceeding that in a comparator cohort with allergic rhinitis (n = 149). Sensitization was associated with poor clinical outcomes, including decreased pulmonary function and more severe disease. "Sensitized bronchiectasis" was classified into two immunoallertypes: one fungal driven and proinflammatory, the other house dust mite driven and chemokine dominant, with the former demonstrating poorer clinical outcome.

    CONCLUSIONS: Allergic sensitization occurs at high frequency in patients with bronchiectasis recruited from different global centers. Improving endophenotyping of sensitized bronchiectasis, a clinically significant state, and a "treatable trait" permits therapeutic intervention in appropriate patients, and may allow improved stratification in future bronchiectasis research and clinical trials.

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