Displaying publications 1 - 20 of 115 in total

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  1. Yeoh AEJ, Lu Y, Chin WHN, Chiew EKH, Lim EH, Li Z, et al.
    J Clin Oncol, 2018 09 10;36(26):2726-2735.
    PMID: 30044693 DOI: 10.1200/JCO.2018.78.3050
    Purpose Although IKZF1 deletion ( IKZF1del) confers a higher risk of relapse in childhood B-cell acute lymphoblastic leukemia (B-ALL), it is uncertain whether treatment intensification will reverse this risk and improve outcomes. The Malaysia-Singapore ALL 2010 study (MS2010) prospectively upgraded the risk assignment of patients with IKZF1del to the next highest level and added imatinib to the treatment of all patients with BCR- ABL1 fusion. Patients and Methods In total, 823 patients with B-ALL treated in the Malyasia-Singapore ALL 2003 study (MS2003; n = 507) and MS2010 (n = 316) were screened for IKZF1del using the multiplex ligation-dependent probe amplification assay. The impact of IKZF1del on the 5-year cumulative incidence of relapse (CIR) was compared between the two studies. Results Patient characteristics were similar in both cohorts, including IKZF1del frequencies (59 of 410 [14.4%] v 50 of 275 [18.2%]; P = .2). In MS2003, where IKZF1del was not used in risk assignment, IKZF1del conferred a significantly higher 5-year CIR (30.4% v 8.1%; P = 8.7 × 10-7), particularly in the intermediate-risk group who lacked high-risk features (25.0% v 7.5%; P = .01). For patients with BCR-ABL1-negative disease, IKZF1del conferred a higher 5-year CIR (20.5% v 8.0%; P = .01). In MS2010, the 5-year CIR of patients with IKZF1del significantly decreased to 13.5% ( P = .05) and no longer showed a significant difference in patients with BCR-ABL1-negative disease (11.4% v 4.4%; P = .09). The 5-year overall survival for patients with IKZF1del improved from 69.6% in MS2003 to 91.6% in MS2010 ( P = .007). Conclusion Intensifying therapy for childhood B-ALL with IKZF1del significantly reduced the risk of relapse and improved overall survival. Incorporating IKZF1del screening significantly improved treatment outcomes in contemporary ALL therapy.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics*
  2. Yeoh AE, Ariffin H, Chai EL, Kwok CS, Chan YH, Ponnudurai K, et al.
    J Clin Oncol, 2012 Jul 1;30(19):2384-92.
    PMID: 22614971 DOI: 10.1200/JCO.2011.40.5936
    PURPOSE: To improve treatment outcome for childhood acute lymphoblastic leukemia (ALL), we designed the Malaysia-Singapore ALL 2003 study with treatment stratification based on presenting clinical and genetic features and minimal residual disease (MRD) levels measured by polymerase chain reaction targeting a single antigen-receptor gene rearrangement.
    PATIENTS AND METHODS: Five hundred fifty-six patients received risk-adapted therapy with a modified Berlin-Frankfurt-Münster-ALL treatment. High-risk ALL was defined by MRD ≥ 1 × 10(-3) at week 12 and/or poor prednisolone response, BCR-ABL1, MLL gene rearrangements, hypodiploid less than 45 chromosomes, or induction failure; standard-risk ALL was defined by MRD ≤ 1 × 10(-4) at weeks 5 and 12 and no extramedullary involvement or high-risk features. Intermediate-risk ALL included all remaining patients.
    RESULTS: Patients who lacked high-risk presenting features (85.7%) received remission induction therapy with dexamethasone, vincristine, and asparaginase, without anthracyclines. Six-year event-free survival (EFS) was 80.6% ± 3.5%; overall survival was 88.4% ± 3.1%. Standard-risk patients (n = 172; 31%) received significantly deintensified subsequent therapy without compromising EFS (93.2% ± 4.1%). High-risk patients (n = 101; 18%) had the worst EFS (51.8% ± 10%); EFS was 83.6% ± 4.9% in intermediate-risk patients (n = 283; 51%).
    CONCLUSION: Our results demonstrate significant progress over previous trials in the region. Three-drug remission-induction therapy combined with MRD-based risk stratification to identify poor responders is an effective strategy for childhood ALL.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy*
  3. Yeoh AE, Lu Y, Chan JY, Chan YH, Ariffin H, Kham SK, et al.
    Leuk. Res., 2010 Mar;34(3):276-83.
    PMID: 19651439 DOI: 10.1016/j.leukres.2009.07.003
    To study genetic epidemiology of childhood acute lymphoblastic leukemia (ALL) in the Chinese and Malays, we investigated 10 polymorphisms encoding carcinogen- or folate-metabolism and transport. Sex-adjusted analysis showed NQO1 609CT significantly protects against ALL, whilst MTHFR 677CT confers marginal protection. Interestingly, we observed that NQO1 609CT and MTHFR 1298 C-allele have greater genetic impact in boys than in girls. The combination of SLC19A1 80GA heterozygosity and 3'-TYMS -6bp/-6bp homozygous deletion is associated with reduced ALL risk in Malay boys. Our study has suggested the importance of gender and race in modulating ALL susceptibility via the folate metabolic pathway.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/ethnology*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics*
  4. Yeoh AE, Li Z, Dong D, Lu Y, Jiang N, Trka J, et al.
    Br J Haematol, 2018 Jun;181(5):653-663.
    PMID: 29808917 DOI: 10.1111/bjh.15252
    Accurate risk assignment in childhood acute lymphoblastic leukaemia is essential to avoid under- or over-treatment. We hypothesized that time-series gene expression profiles (GEPs) of bone marrow samples during remission-induction therapy can measure the response and be used for relapse prediction. We computed the time-series changes from diagnosis to Day 8 of remission-induction, termed Effective Response Metric (ERM-D8) and tested its ability to predict relapse against contemporary risk assignment methods, including National Cancer Institutes (NCI) criteria, genetics and minimal residual disease (MRD). ERM-D8 was trained on a set of 131 patients and validated on an independent set of 79 patients. In the independent blinded test set, unfavourable ERM-D8 patients had >3-fold increased risk of relapse compared to favourable ERM-D8 (5-year cumulative incidence of relapse 38·1% vs. 10·6%; P = 2·5 × 10-3 ). ERM-D8 remained predictive of relapse [P = 0·05; Hazard ratio 4·09, 95% confidence interval (CI) 1·03-16·23] after adjusting for NCI criteria, genetics, Day 8 peripheral response and Day 33 MRD. ERM-D8 improved risk stratification in favourable genetics subgroups (P = 0·01) and Day 33 MRD positive patients (P = 1·7 × 10-3 ). We conclude that our novel metric - ERM-D8 - based on time-series GEP after 8 days of remission-induction therapy can independently predict relapse even after adjusting for NCI risk, genetics, Day 8 peripheral blood response and MRD.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma
  5. Yap LF, Lee D, Khairuddin A, Pairan MF, Puspita B, Siar CH, et al.
    Oral Dis, 2015 Oct;21(7):850-7.
    PMID: 25580884 DOI: 10.1111/odi.12309
    NOTCH signalling can exert oncogenic or tumour suppressive effects in both solid and haematological malignancies. Similar to T-cell acute lymphoblastic leukaemia (T-ALL), early studies suggested a pro-tumorigenic role of NOTCH in head and neck squamous cell carcinoma (HNSCC), mainly based on the increased expression levels of the genes within the pathway. Recently, data from exome sequencing analyses unexpectedly pointed to a tumour suppressor role for NOTCH in HNSCC by identifying loss-of-function mutations in the NOTCH1 gene in a significant proportion of patients. These data have questioned the accepted role of NOTCH in HNSCC and the possible rationale of targeting NOTCH in this disease. This review summarises the current information on NOTCH signalling in HNSCC and discusses how this pathway can apparently exert opposing effects within the same disease.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma
  6. Wong RS, Mohamed SM, Nadarajah VD, Tengku IA
    PMID: 20591169 DOI: 10.1186/1756-9966-29-86
    Various strains of Bacillus thuringiensis (Bt) have been found to produce parasporal proteins that are cytotoxic to human cancer cells. This study aims to establish the binding affinity of purified Bt 18 toxin for CEM-SS (T lymphoblastic leukaemia cell line), to determine if competition exists between the toxin and commercial anticancer drugs for the binding site on CEM-SS and to localise the binding site of the toxin on CEM-SS.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology
  7. Wan Rosalina WR, Teh LK, Mohamad N, Nasir A, Yusoff R, Baba AA, et al.
    J Clin Pharm Ther, 2012 Apr;37(2):237-41.
    PMID: 21545474 DOI: 10.1111/j.1365-2710.2011.01272.x
    Genetic polymorphisms of thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphohydrolase (ITPA 94C>A) contribute to variable responses, including fatal adverse effects, among subjects treated with 6-mercaptopurine (6-MP). Our objectives were to investigate the distribution of specific TPMT and ITPA genotypes in healthy subjects and patients with acute lymphoblastic leukaemia (ALL) from the three main ethnic groups (Malays, Chinese and Indians) in Malaysia and the association of the polymorphisms with adverse effects of 6-MP.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
  8. Venkataraghavan K, Majithia U, Choudhary P, Trivedi K, Shah S
    J Contemp Dent Pract, 2016 Jan-Feb;15(5):614-7.
    PMID: 25707835
    INTRODUCTION: Leukemia is a malignancy of the bone marrow and constitutes 30% of all childhood cancers. The leukemic condition itself and its therapy cause oral signs and symptoms with significant morbidity.
    AIMS AND OBJECTIVES: The aim of this study was to review the oral health status in children with leukemia and relate the gingival and periodontal findings to the changes in their hematological values.
    MATERIALS AND METHOD: The oral health status in 47 pediatric leukemic patients in the age group of 6 to 14 years was assessed using the dmft/DMFT index, OHI(S) index and modified gingival index (MGI). Their hematological reports on the day of examination were obtained. The patients were divided into three groups based on the status of treatment. The relation between the platelet count and the WBC count with the MGI score was checked.
    RESULTS: The highest dmf and DMF scores were seen in patients who were currently under treatment. Though an inverse relation was seen between the platelet count and the MGI score, a statistically significant value was not obtained.
    CONCLUSION: A longitudinal follow-up of patients should be carried out in order to establish a relation between the hematological parameters and the gingival inflammation score
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma/radiotherapy
  9. Tuck, Sang Hoe, Kok, Wai Chum
    MyJurnal
    A five-week-old infant presented with infantile acute lymphoblastic leukaemia. He devel-oped an early CNS and bone marrow relapse despite intensive treatment. This paper discusses infantile leukaemia and its treatment.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma
  10. Teh HS, Fadilah SA, Leong CF
    Singapore Med J, 2007 Feb;48(2):e46-9.
    PMID: 17304378
    Transverse myelopathy is one of the rare complications following administration of intrathecal chemotherapy. We report two cases of transverse myelopathy following administration of intrathecal methotrexate and cytarabine arabinoside. One patient was a 17-year-old Malay man who had lymphoblastic lymphoma in the leukaemic phase, while the other patient was a 40-year-old Malay man with relapsed Hodgkin's lymphoma. Both cases demonstrated variability in onset of symptoms, clinical progression and final outcome from the complication.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
  11. Tay CG, Lee VWM, Ong LC, Goh KJ, Ariffin H, Fong CY
    Pediatr Blood Cancer, 2017 Aug;64(8).
    PMID: 28139029 DOI: 10.1002/pbc.26471
    BACKGROUND: Vincristine, an essential component of childhood acute lymphoblastic leukaemia (ALL) therapeutic protocols, is associated with dose-dependent neurotoxicity, but its long-term morbidity in treated children has not been clearly elucidated. The aim of this study is to determine the prevalence of vincristine-induced peripheral neuropathy (VIPN) among Malaysian childhood ALL survivors and its impact on motor function and quality of life.

    PROCEDURE: Survivors of childhood ALL aged 4-18 years who had completed chemotherapy for 2 years or more were evaluated for VIPN using both the clinical Total Neuropathy Score (cTNS) and nerve conduction studies. Motor function and quality of life of the survivors were assessed via the Bruininks-Oseretsky Test of Motor Proficiency Brief Form, Second Edition (BOT-2 Brief Form) and the Paediatric Quality of Life version 4.0 Generic Core Scales (PedsQL4.0) questionnaire, respectively.

    RESULTS: One hundred and one survivors with a duration of follow-up ranging from 2.0 to 10.3 years were recruited. Twenty-seven (26.7%) had abnormal cTNS scores and 69 (68.3%) had electrophysiological evidence of neuropathy. Of these, 16 (15.8%) had combined clinical and electrophysiological neuropathy (VIPN). Those previously treated on the intermediate- or high-risk treatment stratification arms had a higher risk of developing VIPN (67.3 vs. 32.7%; odds ratio [OR]: 9.06, 95% confidence interval [CI]: 1.14-71.86; P = 0.014). Survivors with VIPN had significantly lower quality of life scores in the physical (P = 0.024) and social domains (P = 0.039) compared with peers without VIPN, but no association with poorer motor function was observed.

    CONCLUSIONS: Sixteen percent of ALL survivors had VIPN. VIPN should be increasingly recognised as a late effect of chemotherapy, as it significantly affects physical and social function quality of life.

    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*
  12. Tang YL, Raja Sabudin RZ, Leong CF, Ko CC, Chia WK, Salwati S, et al.
    Malays J Pathol, 2015 Dec;37(3):275-9.
    PMID: 26712675 MyJurnal
    A rare case of double Philadelphia chromosome-positive B Acute lymphoblastic Leukaemia (B-ALL) is reported here. A 60-year-old lady presented with one month history of fever, submandibular lymphadenopathy, loss of appetite and weight loss. Physical examination revealed multiple palpable cervical lymph nodes. Blood film showed leucocytosis with 72% blasts. Bone marrow assessment confirmed a diagnosis of B-ALL with presence of double Philadelphia (Ph) chromosomes. As she was very ill, she was initially treated with an attenuated regimen of induction chemotherapy consisting of rituximab, cyclophosphamide, vincristine and prednisolone (R-CVP) along with intrathecal chemotherapy comprising methotrexate, cytarabine and hydrocortisone. Bone marrow examination post-induction chemotherapy showed >5% blasts. She was subsequently re-induced with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) along with intrathecal chemotherapy, following which she went into complete remission. Consolidation chemotherapy consisting of methotrexate, methylprednisolone, cytarabine, intrathecal chemotherapy and imatinib was subsequently administered followed by maintenance chemotherapy consisting of vincristine, prednisolone and imatinib (IDEAMOP). She developed spontaneous bruises and relapsed four months into her maintenance chemotherapy with 90% blasts in the bone marrow which was treated with fludarabine, cytarabine and granulocyte colony stimulating factor (FLAG). Unfortunately she developed neutropenic sepsis which was complicated by invasive lung aspergillosis. Bone marrow examination post-FLAG showed 80% blasts. Despite aggressive antifungal therapy, her lung infection worsened and she finally succumbed to her illness 13 months after the initial diagnosis. We highlight a rare case of elderly B-ALL with double Ph chromosomes which carries a poor prognosis despite aggressive treatment for the disease and its complications.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics*
  13. Tan SY, Poh BK, Nadrah MH, Jannah NA, Rahman J, Ismail MN
    J Hum Nutr Diet, 2013 Jul;26 Suppl 1:23-33.
    PMID: 23701375 DOI: 10.1111/jhn.12074
    The assessment of nutritional status among paediatric patients is important for the planning and execution of nutritional strategies that strive to optimise the quality of life and growth among sick children. The present study aimed to evaluate the nutritional status and dietary intake among children with acute leukaemia.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
  14. Tan SY, Poh BK, Chong HX, Ismail MN, Rahman J, Zarina AL, et al.
    Leuk. Res., 2013 Jan;37(1):14-20.
    PMID: 23099236 DOI: 10.1016/j.leukres.2012.09.005
    This study aimed to assess the physical activity levels of pediatric patients with acute leukemia undergoing chemotherapy. Thirty-eight pediatric patients and matched controls, aged 3-12 years old, were measured for weight, height, and other anthropometric parameters. Physical activity was assessed using actical accelerometer and activity log book. Patients recorded significantly lower mean total activity counts (26.2±30.2 cpm vs. 192.2±68.8 cpm; p<0.01) and spent more time in sedentary activities (1301±121 min vs. 1020±101 min; p<0.001) compared to controls. They also achieved fewer 1-5-min bouts of moderate-vigorous physical activity (MVPA) compared to controls (1.50±5.95 vs. 37.38±40.36; p<0.001). In conclusion, patients had lower physical activity level and intensity; and simple exercise intervention programs may be needed to minimize the detrimental effects of prolonged sedentary behaviors.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma/physiopathology*
  15. Tan R, Ng KP, Gan GG, Na SL
    Med J Malaysia, 2013 Dec;68(6):479-80.
    PMID: 24632920 MyJurnal
    In the past two decades, Fusarium species have been increasingly recognized as serious pathogens in immunocompromised patients. The outcome of fusariosis in the context of severe persistent neutropaenia has been almost universally fatal. The treatment of fusariosis in immunocompromised patients remains a challenge and the prognosis of systemic fusariosis in this population remains poor. This report presents a case of fatal fusariosis in a 37- year-old patient who was diagnosed with precursor-B cell Acute Lymphoblastic Leukaemia (ALL).
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma
  16. Tan AK, Azman A, Hoe TS, Rohana T
    Med J Malaysia, 1994 Dec;49(4):409-11.
    PMID: 7674978
    A six-year-old boy, a known case of acute lymphoblastic leukaemia (ALL) on remission since 1991 presented with leukocoria and poor vision of the left eye for two days' duration. Examination revealed endophthalmitis in the left eye with raised intraocular pressure. Anterior chamber paracentesis with vitreous biopsy confirmed a diagnosis of ocular involvement. Further investigation revealed that he also had bone marrow and central nervous system relapse. Clinical manifestation and treatment modalities of ocular involvement in leukaemia are discussed.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology*
  17. TI TS
    Med J Malaya, 1962 Mar;16:214-8.
    PMID: 13921142
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma*
  18. 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.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics
  19. Sulong S
    Malays J Med Sci, 2010 Jul;17(3):5-12.
    PMID: 22135543
    Screening of the entire human genome using high-density single nucleotide polymorphism array (SNPA) has become a powerful technique used in cancer genetics and population genetics studies. The GeneChip® Mapping Array, introduced by Affymetrix, is one SNPA platform utilised for genotyping studies. This GeneChip system allows researchers to gain a comprehensive view of cancer biology on a single platform for the quantification of chromosomal amplifications, deletions, and loss of heterozygosity or for allelic imbalance studies. Importantly, this array analysis has the potential to reveal novel genetic findings involved in the multistep development of cancer. Given the importance of genetic factors in leukaemogenesis and the usefulness of screening the whole genome, SNPA analysis has been utilised in many studies to characterise genetic aberrations in childhood acute lymphoblastic leukaemia.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma
  20. Shiun Chuen C, Md Daud MK, Che Jalil NA, Hazmi H
    Med J Malaysia, 2017 10;72(5):318-320.
    PMID: 29197892 MyJurnal
    A patient presenting with an ear polyp is a common finding in otorhinolaryngology practice. The common causes include chronic otitis media and cholesteatoma. We report an adult female patient with a history of acute leukaemia presenting with chronic otitis media symptoms and right ear polyp. She was subsequently diagnosed as relapse of B-cell acute lymphoblastic leukaemia based on histopathological examination. The presentation may be similar to an inflammatory pathology of the middle ear, making it misleading.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis*
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