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  1. Fulltext Double Philadelphia chromosome-positive B acute lymphoblastic leukaemia in an elderly patient
    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
  2. Physical activity of pediatric patients with acute leukemia undergoing induction or consolidation chemotherapy
    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
  3. Vincristine-induced vocal cord palsy: case report and review of the literature
    Latiff ZA, Kamal NA, Jahendran J, Alias H, Goh BS, Syed Zakaria SZ, et al.
    J Pediatr Hematol Oncol, 2010 Jul;32(5):407-10.
    PMID: 20505534 DOI: 10.1097/MPH.0b013e3181e01584
    Vincristine-induced vocal cord paralysis is a rare but serious complication. We report 2 patients with acute lymphoblastic leukemia who developed progressive stridor during induction chemotherapy. There were no clinical features of peripheral or autonomic neuropathy. Flexible laryngoscopy confirmed the diagnosis of bilateral vocal cord palsy; interestingly, the nerve conduction test revealed axonal motor neuropathy involving the median and common peroneal nerves in both patients. The first patient required prolonged ventilatory support necessitating unilateral cordectomy before extubation, whereas the second only required supplemental oxygen therapy. There was resolution of stridor in the first patient after cordectomy and gradual clinical improvement in the second. These cases illustrate that a high index of suspicion of vincristine-induced vocal cord palsy with prompt otolaryngology consultation for laryngoscopy is required in the diagnostic evaluation of a patient who has received vincristine.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*
  4. Fulltext Transient hyperthyroidism following L-asparaginase therapy for acute lymphoblastic leukemia
    Fadilah SAW, Faridah I, Cheong SK
    Med J Malaysia, 2000 Dec;55(4):513-5.
    PMID: 11221167
    The effect of L-asparaginase on the thyroid gland has not been well documented. We report the first two cases of hyperthyroidism associated with thyroid nodule following L-asparaginase therapy for acute lymphoblastic leukemia (ALL). The thyroid function abnormalities were not severe, short-lived and did not require specific therapy.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*
  5. Extensive intracranial haemorrhage as a complication of acute lymphoblastic leukaemia with hyperleukocytosis
    Lim WK, Fong CY, Li L, Foo JC, Yap TY
    J Clin Neurosci, 2019 Jun;64:11-14.
    PMID: 30948308 DOI: 10.1016/j.jocn.2019.03.056
    We report a rare case of distinctive extensive punctate intracranial haemorrhage associated with acute lymphoblastic leukaemia with hyperleukocytosis. A 7-year-old girl presented with hyperleukocytosis (white cell count 788.7 × 109/L; 94% peripheral blasts) and laboratory tumour lysis syndrome. The diagnosis of T-cell acute lymphoblastic leukaemia was established and confirmed by immunophenotyping of peripheral blood and chemotherapy was commenced promptly. On day 3 of treatment, she developed progressive encephalopathy, left sided hemiparesis with left 6th and upper motor neuron 7th cranial nerve palsy. Brain MRI scan showed extensive punctate haemorrhages with perilesional oedema over the frontal, parietal, occipital, temporal, brainstem and cerebellar regions. The lesions were predominantly over the juxtacortical grey matter. She made a full neurological recovery after 3 months. Our report widens the neuroradiological features of intracranial haemorrhage associated with hyperleukocytosis and highlights the importance of prompt chemotherapy in these patients.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
  6. Successful toxicity reduction during delayed intensification in the non-high-risk arm of Malaysia-Singapore Acute Lymphoblastic Leukaemia 2010 study
    Oh BLZ, Lee SHR, Foo KM, Chiew KH, Seeto ZZL, Chen ZW, et al.
    Eur J Cancer, 2021 01;142:92-101.
    PMID: 33246161 DOI: 10.1016/j.ejca.2020.10.010
    In non-high-risk (non-HR) patients, the Malaysia-Singapore Acute Lymphoblastic Leukaemia 2003 (MS2003) study achieved good outcomes. However, its delayed-intensification (DI) phase, comprising repeated blocks of protocol III (2003-PIII), was toxic and caused significant treatment delays. The successor MS2010 study attempted to lower DI toxicity by replacing myelosuppressive drugs (doxorubicin, cytarabine) with vincristine and asparaginase.

    PATIENTS AND METHODS: We analysed 1748 admissions for fever in 315 Singapore children with non-HR acute lymphoblastic leukaemia (ALL) (MS2003, n = 183; MS2010, n = 132), comprising 76% of the total cohort (n = 413), to study the impact of these changes.

    RESULTS: The new 2010-PVa which has no doxorubicin, was associated with significantly fewer hospitalisations due to fever (0.08 versus 0.30 admissions per block [A/blk], p 

    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*
  7. Relationship between oral health status and hematological values in pediatric leukemic patients: an evaluative survey
    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/drug therapy
  8. Fulltext Host genetic variants of ABCB1 and IL15 influence treatment outcome in paediatric acute lymphoblastic leukaemia
    Lu Y, Kham SK, Ariffin H, Oei AM, Lin HP, Tan AM, et al.
    Br. J. Cancer, 2014 Mar 18;110(6):1673-80.
    PMID: 24434428 DOI: 10.1038/bjc.2014.7
    Host germline variations and their potential prognostic importance is an emerging area of interest in paediatric ALL.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
  9. Fulltext Disseminated Geotrichum infection
    Ng KP, Soo-Hoo TS, Koh MT, Kwan PW
    Med J Malaysia, 1994 Dec;49(4):424-6.
    PMID: 7674982
    Intensive chemotherapy has prolonged survival in cancer patients. Unfortunately it has also predisposed them to unusual infections because of their immunocompromised state. We report a case of fungal septicaemia caused by Geotrichum candidum, an imperfect yeast of low virulence in a young girl with acute lymphoblastic leukaemia. It was successfully treated with amphotericin B. The morphological characteristics of this fungus leading to its identification are described.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*
  10. Assessing changes in microstructural integrity of white matter tracts in children with leukaemia following exposure to chemotherapy
    Ramli N, Lim CH, Rajagopal R, Tan LK, Seow P, Ariffin H
    Pediatr Radiol, 2020 08;50(9):1277-1283.
    PMID: 32591982 DOI: 10.1007/s00247-020-04717-x
    BACKGROUND: Intrathecal and intravenous chemotherapy, specifically methotrexate, might contribute to neural microstructural damage.

    OBJECTIVE: To assess, by diffusion tensor imaging, microstructural integrity of white matter in paediatric patients with acute lymphoblastic leukaemia (ALL) following intrathecal and intravenous chemotherapy.

    MATERIALS AND METHODS: Eleven children diagnosed with de novo ALL underwent MRI scans of the brain with diffusion tensor imaging (DTI) prior to commencement of chemotherapy and at 12 months after diagnosis, using a 3-tesla (T) MRI scanner. We investigated the changes in DTI parameters in white matter tracts before and after chemotherapy using tract-based spatial statistics overlaid on the International Consortium of Brain Mapping DTI-81 atlas. All of the children underwent formal neurodevelopmental assessment at the two study time points.

    RESULTS: Whole-brain DTI analysis showed significant changes between the two time points, affecting several white matter tracts. The tracts demonstrated longitudinal changes of decreasing mean and radial diffusivity. The neurodevelopment of the children was near compatible for age at the end of ALL treatment.

    CONCLUSION: The quantification of white matter tracts changes in children undergoing chemotherapy showed improving longitudinal values in DTI metrics (stable fractional anisotropy, decreasing mean and radial diffusivity), which are incompatible with deterioration of microstructural integrity in these children.

    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*
  11. Fulltext Parental reports of behavioural outcome among paediatric leukaemia survivors in Malaysia: a single institution experience
    Hamidah A, Sham Marina M, Tamil AM, Loh CK, Zarina LA, Jamal R, et al.
    Trop Med Int Health, 2014 Oct;19(10):1177-84.
    PMID: 25047756 DOI: 10.1111/tmi.12358
    To determine the behavioural impact of chemotherapy in survivors of acute lymphoblastic leukaemia (ALL) treated with chemotherapy only and to identify treatment-related or sociodemography-related factors that might be associated with behavioural outcome.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*
  12. Intensifying Treatment of Childhood B-Lymphoblastic Leukemia With IKZF1 Deletion Reduces Relapse and Improves Overall Survival: Results of Malaysia-Singapore ALL 2010 Study
    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*
  13. The differential metabolite profiles of acute lymphoblastic leukaemic patients treated with 6-mercaptopurine using untargeted metabolomics approach
    Bannur Z, Teh LK, Hennesy T, Rosli WR, Mohamad N, Nasir A, et al.
    Clin Biochem, 2014 Apr;47(6):427-31.
    PMID: 24582698 DOI: 10.1016/j.clinbiochem.2014.02.013
    Acute lymphoblastic leukaemia (ALL) has posed challenges to the clinician due to variable patients' responses and late diagnosis. With the advance in metabolomics, early detection and personalised treatment are possible.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*
  14. Fulltext Minimal residual disease-guided treatment deintensification for children with acute lymphoblastic leukemia: results from the Malaysia-Singapore acute lymphoblastic leukemia 2003 study
    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
  15. Polymorphism of ITPA 94C>A and risk of adverse effects among patients with acute lymphoblastic leukaemia treated with 6-mercaptopurine
    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
  16. Fulltext Characterisation of the binding properties of Bacillus thuringiensis 18 toxin on leukaemic cells
    Wong RS, Mohamed SM, Nadarajah VD, Tengku IA
    J Exp Clin Cancer Res, 2010;29:86.
    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
  17. Age, sex, haemoglobin level, and white cell count at diagnosis are important prognostic factors in children with acute lymphoblastic leukemia treated with BFM-type protocol
    Ng SM, Lin HP, Ariffin WA, Zainab AK, Lam SK, Chan LL
    J Trop Pediatr, 2000 Dec;46(6):338-43.
    PMID: 11191144
    The presenting features and treatment outcome for 575 Malaysian children (< or = 12 years of age) with newly diagnosed acute lymphoblastic leukemia (ALL), admitted to the University Hospital, Kuala Lumpur, Malaysia between 1 January 1980 and 30 May 1995 were evaluated to determine their prognostic significance. Two-year overall survival was achieved in 67 per cent of all patients and 55 per cent of patients were relapse-free at 2 years. All except 10 patients, with identified French-American-British L3 morphology were treated with the modified Berlin-Frankfurt-Munster 78 treatment protocol. Univariate analyses of failure rate conferred age, sex, white cell count and hemoglobin level as potentially significant prognostic factors. All four presenting features retained their prognostic strength in a multivariate analysis. Race, platelet count, morphological subtype, liver/spleen size, lymphadenopathy, central nervous system and mediastinal mass involvement did not show any significant effect on treatment outcome. The 2-year survival rate was significantly different with regard to age, white cell count and hemoglobin level. However, sex was not significantly related to overall survival. These prognostic factors may have implications on future stratification of risk-adjusted initial treatment in the management of childhood ALL. Our analysis of Malaysian children is similar to what could be predicted based on previous studies in other populations.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*
  18. Streptokinase infusion for asparaginase-induced arterial thrombosis
    Omar KZ, Ariffin H, Abdullah WA, Chan LL, Lin HP
    Med. Pediatr. Oncol., 2000 May;34(5):377-8.
    PMID: 10797367
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
  19. Fulltext Ocular involvement in acute lymphoblastic leukaemia
    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/drug therapy
  20. Retinopathy in acute leukaemia at initial diagnosis: correlation of fundus lesions and haematological parameters
    Reddy SC, Jackson N
    Acta Ophthalmol Scand, 2004 Feb;82(1):81-5.
    PMID: 14738490
    PURPOSE: To determine the prevalence of retinal changes in newly diagnosed acute leukaemia patients, and to establish the relationship between retinal lesions and haematological parameters in these patients.

    METHODS: A total of 127 patients with acute leukaemia (myeloid and lymphoid), of both genders, aged between 13 and 77 years, were examined by an ophthalmologist for retinal changes using direct/indirect ophthalmoscopy within 2 days of diagnosis before starting chemotherapy.

    RESULTS: Retinal lesions were seen in 62 cases (49%), with intraretinal haemorrhages being the most common lesion (42%). A high white blood cell count was significantly associated with intraretinal haemorrhages (p = 0.04) and white-centred haemorrhages (p = 0.001), while a low platelet count was significantly associated with intraretinal haemorrhages (p = 0.03) in acute myeloid leukaemia patients.

    CONCLUSIONS: A high white blood cell count may be considered as important as a low platelet count in the pathogenesis of leukaemic retinopathy.

    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
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