Displaying publications 21 - 40 of 111 in total

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  1. Fulltext Cytogenetics and molecular genetic tests for the diagnosis and treatment of chronic myeloid leukemia
    Mohd Khairi Zahry, Ankathil, Ravindran
    Buletin Persatuan Genetik Malaysia, 2008;14(1):9-11.
    MyJurnal
    Chronic Myeloid Leukemia (CML) is a clonal disorder thought to originate in a single abnormal haematopoietic stem cell. This myeloproliferative fatal stem cell disorder comprises
    approximately 14% of all leukemias. In most cases, CML runs a triphasic course, which includes an initial chronic phase that transforms eventually into a blastic phase resembling acute leukemia. In 60%- 80% of patients, an intermediate or accelerated phase precedes the terminal blastic phase. Accelerated phase and blastic phase sometimes are lumped together and considered to be
    advanced phase CML. The entire continuum from chronic phase to blastic phase lasts a median of 3 to 5 years . This time period can be broken down in to the chronic phase which if untreated,
    lasts for 2 to 5 years and finally the fatal blastic phase, which lasts from 3 to 6 months. A patient can present in any of these 3 stages.
    Matched MeSH terms: Leukemia, Myeloid, Chronic-Phase
  2. Aberrant DNA Methylation of SOCS1 Gene is Not Associated with Resistance to Imatinib Mesylate among Chronic Myeloid Leukemia Patients
    Elias MH, Azlan H, Baba AA, Ankathil R
    Cardiovasc Hematol Disord Drug Targets, 2018;18(3):234-238.
    PMID: 29669505 DOI: 10.2174/1871529X18666180419101416
    BACKGROUND: In exploring the cause of Imatinib Mesylate (IM) resistance among Chronic Myeloid Leukemia (CML) patients who do not harbor BCR-ABL dependent mechanism, BCR-ABL independent pathways are the most probable pathways that should be explored. In BCR-ABL independent pathway, SOCS1 plays an important role as it helps in regulating optimal JAK/STAT activity.

    OBJECTIVE: To identify the association of SOCS1 gene hypermethylation in mediating IM Resistance.

    METHOD: The SOCS1 promoter methylation level of 92 BCR-ABL non mutated IM resistant CML patients, 83 IM good response CML patients and 5 normal samples from healthy individuals were measured using Methylation Specific-High Resolution Melt (MS-HRM) analysis.

    RESULTS: Both primers used to amplify promoter region from -333 to -223 and from -332 to -188 showed less than 10% methylation in all CML and normal samples. Consequently, there was no significant difference in SOCS1 promoter methylation level between IM resistant and IM good response patients.

    CONCLUSION: SOCS1 promoter methylation level is not suitable to be used as one of the biomarkers for predicting the possibility of acquiring resistance among CML patients treated with IM.

    Matched MeSH terms: Leukemia, Myeloid/drug therapy*; Leukemia, Myeloid/genetics*; Leukemia, Myeloid/pathology
  3. siRNA-mediated inhibition of survivin gene enhances the anti-cancer effect of etoposide in U-937 acute myeloid leukemia cells
    Jafarlou M, Baradaran B, Shanehbandi D, Saedi TA, Jafarlou V, Ismail P, et al.
    Cell Mol Biol (Noisy-le-grand), 2016 May 30;62(6):44-9.
    PMID: 27262801
    Acute myeloid leukemia (AML) is one of the most frequent types of leukemia which mostly affects adult people. Resistance to therapeutic drugs is considered as a major clinical concern resulting in a weaker response to chemotherapy, disease relapse and decreased survival rate. Survivin, a member of Inhibitor of Apoptosis Proteins (IAPs), is associated with drug resistance and inhibition of apoptotic mechanisms in numerous hematological malignancies. In the present study, we examined the combined effect of etoposide and siRNA-mediated silencing of survivin on U-937 acute myeloid leukemia cells. The AML cells were transfected with survivin specific siRNA and gene knockdown was confirmed by quantitative real time PCR and western blotting. Subsequently, U-937 cells were assessed for response to etoposide treatment and apoptosis rate was measured with flowcytometery. The cytotoxic effects in siRNA-etoposide group were measured and compared to etoposide single therapy group. Survivin siRNA effectively knocked down the mRNA and protein levels of survivin, which led to lower cell proliferation and enhanced apoptosis. Furthermore, combined treatment of etoposide and survivin siRNA synergistically increased the cell toxic effects of etoposide and its ability to induce apoptosis.
    Matched MeSH terms: Leukemia, Myeloid, Acute/drug therapy*; Leukemia, Myeloid, Acute/genetics*
  4. Congenital papulonodular eruption: presenting sign of congenital leukaemia cutis
    Nanda A, El-Kamel MF, Al-Oneizi EM, Al-Ajmi M, Al-Enezi EM, Madda JP
    Clin Exp Dermatol, 2012 Jul;37(5):509-11.
    PMID: 22712859 DOI: 10.1111/j.1365-2230.2011.04270.x
    Congenital leukaemia (CL) is a rare malignancy that accounts for < 1% of cases of childhood leukaemias. Leukaemia cutis (LC) refers to cutaneous infiltration with leukaemic cells, and is seen in 30-50% of CL cases. It may precede, follow or occur simultaneously with leukaemia. If left untreated, the prognosis is usually poor, but early diagnosis and treatment may result in a favourable prognosis. We report a case of congenital leukaemia cutis with a progressive, violaceous papulonodular eruption (a 'blueberry muffin' rash), which had been noted at birth, as a presenting sign of acute myeloid leukaemia (AML), which on investigation was classified as AML, FAB M2 type with a t(8; 21)(p11;q22) chromosomal defect. The patient had a favourable response to AML chemotherapy.
    Matched MeSH terms: Leukemia, Myeloid, Acute/congenital*; Leukemia, Myeloid, Acute/pathology
  5. Retinal findings in adult leukaemia: correlation with leukocytosis
    Jackson N, Reddy SC, Hishamuddin M, Low HC
    Clin Lab Haematol, 1996 Jun;18(2):105-9.
    PMID: 8866143
    The associations between retinal findings and haematological parameters in acute leukaemia are controversial. Sixty-three newly-diagnosed acute leukaemia patients, aged 12-77 years, were studied prospectively for the presence of intra-retinal haemorrhages (IRH), white-centred haemorrhages (WCH), cotton wool spots (CWS) and macular haemorrhages (MH), Thirty-three patients (52.4%) showed at least one retinal abnormality. The prevalence of individual findings was: IRH (30 cases), WCH (20 cases), CWS (5 cases), MH (11 cases). In contrast to previous studies, there was no association between any of these retinal findings and the haemoglobin level or the platelet count. There was a higher median WBC in patients with IRH (68 x 10(9)/l) than in those without IRH (15.4 x 10(9)/l), P = 0.037. When the acute myeloblastic leukaemia cases were considered separately, an association was also found between higher WBC and the presence of WCH and CWS. There was no association between retinal findings and FAB type in the AML cases. We conclude that a high WBC may be at least as important as anaemia and thrombocytopenia in the pathogenesis of the retinopathy of acute leukaemia.
    Matched MeSH terms: Leukemia, Myeloid/blood; Leukemia, Myeloid/complications; Leukemia, Myeloid/pathology
  6. Excellent Survival Outcomes of Pediatric Patients With Acute Myeloid Leukemia Treated With the MASPORE 2006 Protocol
    Sutiman N, Nwe MS, Ni Lai EE, Lee DK, Chan MY, Eng-Juh Yeoh A, et al.
    Clin Lymphoma Myeloma Leuk, 2021 03;21(3):e290-e300.
    PMID: 33384264 DOI: 10.1016/j.clml.2020.11.016
    PURPOSE: To determine the prognostic factors in pediatric patients with acute myeloid leukemia (AML) and to assess whether their outcomes have improved over time.

    PATIENTS AND METHODS: Sixty-two patients with AML excluding acute promyelocytic leukemia were retrospectively analyzed. Patients in the earlier cohort (n = 36) were treated on the Medical Research Council (MRC) AML12 protocol, whereas those in the recent cohort (n = 26) were treated on the Malaysia-Singapore AML protocol (MASPORE 2006), which differed in terms of risk group stratification, cumulative anthracycline dose, and timing of hematopoietic stem-cell transplantation for high-risk patients.

    RESULTS: Significant improvements in 10-year overall survival and event-free survival were observed in patients treated with the recent MASPORE 2006 protocol compared to the earlier MRC AML12 protocol (overall survival: 88.0% ± 6.5% vs 50.1% ± 8.6%, P = .002; event-free survival: 72.1% ± 9.0 vs 50.1% ± 8.6%, P = .045). In univariate analysis, patients in the recent cohort had significantly lower intensive care unit admission rate (11.5% vs 47.2%, P = .005) and numerically lower relapse rate (26.9% vs 50.0%, P = .068) compared to the earlier cohort. Multivariate analysis showed that treatment protocol was the only independent predictive factor for overall survival (hazard ratio = 0.21; 95% confidence interval, 0.06-0.73, P = .014).

    CONCLUSION: Outcomes of pediatric AML patients have improved over time. The more recent MASPORE 2006 protocol led to significant improvement in long-term survival rates and reduction in intensive care unit admission rate.

    Matched MeSH terms: Leukemia, Myeloid, Acute/diagnosis; Leukemia, Myeloid, Acute/mortality*; Leukemia, Myeloid, Acute/therapy*
  7. Fulltext Multiplexed automated digital quantification of fusion transcripts: comparative study with fluorescent in-situ hybridization (FISH) technique in acute leukemia patients
    Akhter A, Mughal MK, Elyamany G, Sinclair G, Azma RZ, Masir N, et al.
    Diagn Pathol, 2016 Sep 15;11(1):89.
    PMID: 27632978 DOI: 10.1186/s13000-016-0541-z
    The World Health Organization (WHO) classification system defines recurrent chromosomal translocations as the sole diagnostic and prognostic criteria for acute leukemia (AL). These fusion transcripts are pivotal in the pathogenesis of AL. Clinical laboratories universally employ conventional karyotype/FISH to detect these chromosomal translocations, which is complex, labour intensive and lacks multiplexing capacity. Hence, it is imperative to explore and evaluate some newer automated, cost-efficient multiplexed technologies to accommodate the expanding genetic landscape in AL.
    Matched MeSH terms: Leukemia, Myeloid, Acute/diagnosis; Leukemia, Myeloid, Acute/genetics*
  8. Fulltext Receptor tyrosine kinase (c-Kit) inhibitors: a potential therapeutic target in cancer cells
    Abbaspour Babaei M, Kamalidehghan B, Saleem M, Huri HZ, Ahmadipour F
    Drug Des Devel Ther, 2016;10:2443-59.
    PMID: 27536065 DOI: 10.2147/DDDT.S89114
    c-Kit, a receptor tyrosine kinase, is involved in intracellular signaling, and the mutated form of c-Kit plays a crucial role in occurrence of some cancers. The function of c-Kit has led to the concept that inhibiting c-Kit kinase activity can be a target for cancer therapy. The promising results of inhibition of c-Kit for treatment of cancers have been observed in some cancers such as gastrointestinal stromal tumor, acute myeloid leukemia, melanoma, and other tumors, and these results have encouraged attempts toward improvement of using c-Kit as a capable target for cancer therapy. This paper presents the findings of previous studies regarding c-Kit as a receptor tyrosine kinase and an oncogene, as well as its gene targets and signaling pathways in normal and cancer cells. The c-Kit gene location, protein structure, and the role of c-Kit in normal cell have been discussed. Comprehending the molecular mechanism underlying c-Kit-mediated tumorogenesis is consequently essential and may lead to the identification of future novel drug targets. The potential mechanisms by which c-Kit induces cellular transformation have been described. This study aims to elucidate the function of c-Kit for future cancer therapy. In addition, it has c-Kit inhibitor drug properties and their functions have been listed in tables and demonstrated in schematic pictures. This review also has collected previous studies that targeted c-Kit as a novel strategy for cancer therapy. This paper further emphasizes the advantages of this approach, as well as the limitations that must be addressed in the future. Finally, although c-Kit is an attractive target for cancer therapy, based on the outcomes of treatment of patients with c-Kit inhibitors, it is unlikely that Kit inhibitors alone can lead to cure. It seems that c-Kit mutations alone are not sufficient for tumorogenesis, but do play a crucial role in cancer occurrence.
    Matched MeSH terms: Leukemia, Myeloid, Acute/drug therapy*; Leukemia, Myeloid, Acute/genetics; Leukemia, Myeloid, Acute/metabolism
  9. Fulltext Tsukamurella tyrosinosolvens intravascular catheter-related bacteremia in a haematology patient: a case report
    Karunakaran R, Halim HA, Ng KP, Hanifah YA, Chin E, Jaafar FL, et al.
    Eur Rev Med Pharmacol Sci, 2011 Nov;15(11):1343-6.
    PMID: 22195371
    Tsukamurella spp. are a rare but important cause of intravascular catheter-related bacteremia in immunocompromised patients. The organism is an aerobic, Gram-positive, weakly acid-fast bacillus that is difficult to differentiate using standard laboratory methods from other aerobic actinomycetales such as Nocardia spp., Rhododoccus spp., Gordonia spp., and the rapid growing Mycobacterium spp. We report a case of Tsukamurella tyrosinosolvens catheter-related bacteremia in a 51-year-old haematology patient who responded to treatment with imipenem and subsequent line removal. 16srRNA sequencing allowed for the prompt identification of this organism.
    Matched MeSH terms: Leukemia, Myeloid; Leukemia, Myeloid, Acute/complications; Leukemia, Myeloid, Acute/drug therapy
  10. Fulltext Job characteristics of a Malaysian bank's anti-money laundering system and its employees' job satisfaction
    Kannan R, Reddiar Y, Ramakrishnan K, Eastaff MS, Ramesh S
    F1000Res, 2021;10:1052.
    PMID: 36225238 DOI: 10.12688/f1000research.73234.2
    Background: Banks and financial institutions are vulnerable to money laundering (ML) as a result of crime proceeds infiltrating banks in the form of significant cash deposits. Improved financial crime compliance processes and systems enable anti-ML (AML) analysts to devote considerable time and effort to case investigation and process quality work, thereby lowering financial risks by reporting suspicious activity in a timely and effective manner. This study uses Job Characteristics Theory (JCT) to evaluate the AML system through the job satisfaction and motivation of its users. The purpose of this study is to determine how satisfied AML personnel are with their jobs and how motivated they are to work with the system. Methods: This cross-sectional study used JCT to investigate the important elements impacting employee satisfaction with the AML system. The five core dimensions of the job characteristics were measured using a job diagnostic survey. The respondents were employees working in the AML department of a Malaysian bank, and the sample group was chosen using a purposive sampling approach. A total of 100 acceptable replies were gathered and analysed using various statistical approaches. A motivating potential score was generated for each employee based on five main job characteristics. Results: Findings revealed that five core job characteristics, namely, skill diversity, task identity, task importance, autonomy and feedback, positively influence the AML system employees' job satisfaction. However, skill variety and autonomy are found to be low, which are reflected in the poor motivating potential score. Conclusion: This study examined the characteristics of the AML system and its users' job satisfaction. Findings revealed that task significance is the most widely recognised characteristic, followed by feedback and task identity. However, there is a lack of skill variety and autonomy, which must be addressed to improve employee satisfaction with the AML system.
    Matched MeSH terms: Leukemia, Myeloid, Acute*
  11. Fulltext Hypomethylating Agents and Immunotherapy: Therapeutic Synergism in Acute Myeloid Leukemia and Myelodysplastic Syndromes
    Wong KK, Hassan R, Yaacob NS
    Front Oncol, 2021;11:624742.
    PMID: 33718188 DOI: 10.3389/fonc.2021.624742
    Decitabine and guadecitabine are hypomethylating agents (HMAs) that exert inhibitory effects against cancer cells. This includes stimulation of anti-tumor immunity in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) patients. Treatment of AML and MDS patients with the HMAs confers upregulation of cancer/testis antigens (CTAs) expression including the highly immunogenic CTA NY-ESO-1. This leads to activation of CD4+ and CD8+ T cells for elimination of cancer cells, and it establishes the feasibility to combine cancer vaccine with HMAs to enhance vaccine immunogenicity. Moreover, decitabine and guadecitabine induce the expression of immune checkpoint molecules in AML cells. In this review, the accumulating knowledge on the immunopotentiating properties of decitabine and guadecitabine in AML and MDS patients are presented and discussed. In summary, combination of decitabine or guadecitabine with NY-ESO-1 vaccine enhances vaccine immunogenicity in AML patients. T cells from AML patients stimulated with dendritic cell (DC)/AML fusion vaccine and guadecitabine display increased capacity to lyse AML cells. Moreover, decitabine enhances NK cell-mediated cytotoxicity or CD123-specific chimeric antigen receptor-engineered T cells antileukemic activities against AML. Furthermore, combination of either HMAs with immune checkpoint blockade (ICB) therapy may circumvent their resistance. Finally, clinical trials of either HMAs combined with cancer vaccines, NK cell infusion or ICB therapy in relapsed/refractory AML and high-risk MDS patients are currently underway, highlighting the promising efficacy of HMAs and immunotherapy synergy against these malignancies.
    Matched MeSH terms: Leukemia, Myeloid, Acute
  12. Gene Mutations as Emerging Biomarkers and Therapeutic Targets for Relapsed Acute Myeloid Leukemia
    Aziz H, Ping CY, Alias H, Ab Mutalib NS, Jamal R
    Front Pharmacol, 2017;8:897.
    PMID: 29270125 DOI: 10.3389/fphar.2017.00897
    It is believed that there are key differences in the genomic profile between adult and childhood acute myeloid leukemia (AML). Relapse is the significant contributor of mortality in patients with AML and remains as the leading cause of cancer death among children, posing great challenges in the treatment of AML. The knowledge about the genomic lesions in childhood AML is still premature as most genomic events defined in children were derived from adult cohorts. However, the emerging technologies of next generation sequencing have narrowed the gap of knowledge in the biology of AML by the detection of gene mutations for each sub-type which have led to the improvement in terms of prognostication as well as the use of targeted therapies. In this review, we describe the recent understanding of the genomic landscape including the prevalence of mutation, prognostic impact, and targeted therapies that will provide an insight into the pathogenesis of AML relapse in both adult and childhood cases.
    Matched MeSH terms: Leukemia, Myeloid, Acute
  13. Construction of a microRNA-mRNA Regulatory Network in De Novo Cytogenetically Normal Acute Myeloid Leukemia Patients
    Esa E, Hashim AK, Mohamed EHM, Zakaria Z, Abu Hassan AN, Mat Yusoff Y, et al.
    Genet Test Mol Biomarkers, 2021 Mar;25(3):199-210.
    PMID: 33734890 DOI: 10.1089/gtmb.2020.0182
    Background: The association between dysregulated microRNAs (miRNAs) and acute myeloid leukemia (AML) is well known. However, our understanding of the regulatory role of miRNAs in the cytogenetically normal AML (CN-AML) subtype pathway is still poor. The current study integrated miRNA and mRNA profiles to explore novel miRNA-mRNA interactions that affect the regulatory patterns of de novo CN-AML. Methods: We utilized a multiplexed nanoString nCounter platform to profile both miRNAs and mRNAs using similar sets of patient samples (n = 24). Correlations were assessed, and an miRNA-mRNA network was constructed. The underlying biological functions of the mRNAs were predicted by gene enrichment. Finally, the interacting pairs were assessed using TargetScan and microT-CDS. We identified 637 significant negative correlations (false discovery rate <0.05). Results: Network analysis revealed a cluster of 12 miRNAs representing the majority of mRNA targets. Within the cluster, five miRNAs (miR-495-3p, miR-185-5p, let-7i-5p, miR-409-3p, and miR-127-3p) were posited to play a pivotal role in the regulation of CN-AML, as they are associated with the negative regulation of myeloid leukocyte differentiation, negative regulation of myeloid cell differentiation, and positive regulation of hematopoiesis. Conclusion: Three novel interactions in CN-AML were predicted as let-7i-5p:HOXA9, miR-495-3p:PIK3R1, and miR-495-3p:CDK6 may be responsible for regulating myeloid cell differentiation in CN-AML.
    Matched MeSH terms: Leukemia, Myeloid, Acute/genetics*
  14. Cell viability of acute myeloid leukaemia blasts in culture correlates with treatment outcome
    Maha A, Cheong SK, Leong CF, Seow HF
    Hematology, 2008 Feb;13(1):13-20.
    PMID: 18534060 DOI: 10.1179/102453308X315762
    Despite the advances in understanding the pathophysiology of acute myeloid leukaemia (AML), the cure rate for acute myeloid leukaemia patients remains low. Cytogenetic abnormalities and age are the prognostic factors that guide treatment decisions. However, many AML patients still die. The biological factors that influence treatment outcome are largely unknown. Thus, the objective of our study was to use the in vitro viability test to correlate with treatment outcome. Acute myeloid leukaemia blasts demonstrated differing ability to survive in culture. Our examination of blast phenotype at various days in culture showed two possible growth directions. First, cells underwent maturation by increased expression of CD16 and down-regulated CD34 (a haemopoietic stem cell marker). These cells also appeared to have undergone apoptosis. Alternatively, cells continued to survive in culture and maintained high expression of CD34. An MTT assay was carried out to determine viability after three days of culture. Lower optical density values were obtained for samples that underwent apoptosis and higher values were obtained for samples that survived in culture. Apoptosis was measured by Annexin V/propidium iodide staining. A comparison between results of MTT assay and duration of disease free survival revealed that a higher viability in vitro correlated significantly with shorter survival duration in the patient (R -0.761, p=0.002, n=13). Thus, this study further supports the hypothesis that AML patients with poor survival may be related to having blasts with a biologically more immature or stem cell-like nature.
    Matched MeSH terms: Leukemia, Myeloid, Acute/drug therapy; Leukemia, Myeloid, Acute/pathology*
  15. Expression of multidrug resistance (MDR) proteins and in vitro drug resistance in acute leukemias
    Fazlina N, Maha A, Jamal R, Zarina AL, Cheong SK, Hamidah H, et al.
    Hematology, 2007 Feb;12(1):33-7.
    PMID: 17364990
    The expression of the multidrug resistance (MDR) proteins may influence the outcome of treatment in patients with acute leukemia. The aim of this study was to determine the IC50 of cytotoxic drugs (cytosine arabinoside, ara-C and daunorubicin, dnr) using the in vitro 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)2H-tetrazolium, inner salt (MTS) assay method. A total of 82 newly diagnosed acute leukemia cases (43 adult myeloid leukaemia, AML cases and 39 acute lymphoblastic leukaemia, ALL cases) and 16 relapsed cases (8 AML cases and 8 ALL cases) were studied. The MTS assay was performed using two cytotoxic drugs, dnr and ara-C. Cells were incubated with different concentrations of drugs for 4 days and the IC50 was extrapolated from the viability curve. In newly diagnosed cases, we found that childhood ALL samples showed higher IC50 values of dnr (0.040 +/- 2.320) compared to adult AML samples (0.021 +/- 0.158). In contrast, newly diagnosed adult AML samples showed higher IC50 values of ara-C (0.157 +/- 0.529) compared to childhood ALL samples (0.100 +/- 2.350). In relapsed cases, two samples of childhood ALL showed IC50 values of dnr (0.910 +/- 1.760) and ara-C (1.310 +/- 2.390), which was higher compared to childhood AML samples (0.129 +/- 0.214 and 0.210 +/- 0.003, respectively). However, there was no correlation between IC50 values of these drugs tested with clinical outcome. In conclusion, we found that MTS assay is an easy, rapid and non laborious method to study in vitro drug resistance in acute leukaemia cases.
    Matched MeSH terms: Leukemia, Myeloid/drug therapy; Leukemia, Myeloid/metabolism
  16. Acute leukaemia masquerading as acute abdomen
    S Abdul Wahid F, Cheong SK, Azman Ali R
    Hosp Med, 2002 Jun;63(6):372-3.
    PMID: 12096671 DOI: 10.12968/hosp.2002.63.6.2011
    Matched MeSH terms: Leukemia, Myeloid/complications*; Leukemia, Myeloid/diagnosis
  17. Fludarabine, High Dose Cytarabine and Granulocyte Colony-Stimulating Factor (FLAG) as Consolidation Chemotherapy in Older Patients with Acute Myeloid Leukemia: A Retrospective Cohort Study
    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.
    Matched MeSH terms: Leukemia, Myeloid, Acute
  18. Myeloid Sarcoma of Temporal Bone: A Rare Manifestation of Relapse Acute Myeloid Leukemia
    Goh BS, Tang CL, Tan GC
    Indian J Otolaryngol Head Neck Surg, 2019 Nov;71(Suppl 2):1023-1026.
    PMID: 31750119 DOI: 10.1007/s12070-015-0930-8
    Myeloid sarcoma is a rare malignant extramedullary neoplasm of myeloid precursor cells. This disorder may occur in concomitance with or precede development of acute or chronic myeloid leukemia. Sometimes, it is the initial manifestation of relapse in a previously treated acute myeloid leukemia. We report a case of 11 years old boy with acute myeloid leukemia in remission state, presented with short history of right otalgia associated with facial nerve palsy. Diagnosis of right acute mastoiditis with facial nerve palsy as complication of acute otitis media was made initially. Patient underwent simple cortical mastoidectomy but histopathology from soft tissue that was sent revealed diagnosis of myeloid sarcoma. A leukemic relapse was confirmed by paediatric oncologist through bone marrow biopsy. Chemotherapy was commenced but patient responded poorly to the treatment.
    Matched MeSH terms: Leukemia, Myeloid, Acute
  19. Fulltext Differential Analysis of Genetic, Epigenetic, and Cytogenetic Abnormalities in AML
    Islam M, Mohamed Z, Assenov Y
    Int J Genomics, 2017;2017:2913648.
    PMID: 28713819 DOI: 10.1155/2017/2913648
    Acute myeloid leukemia (AML) is a haematological malignancy characterized by the excessive proliferation of immature myeloid cells coupled with impaired differentiation. Many AML cases have been reported without any known cytogenetic abnormalities and carry no mutation in known AML-associated driver genes. In this study, 200 AML cases were selected from a publicly available cohort and differentially analyzed for genetic, epigenetic, and cytogenetic abnormalities. Three genes (FLT3, DNMT3A, and NPMc) are found to be predominantly mutated. We identified several aberrations to be associated with genome-wide methylation changes. These include Del (5q), T (15; 17), and NPMc mutations. Four aberrations-Del (5q), T (15; 17), T (9; 22), and T (9; 11)-are significantly associated with patient survival. Del (5q)-positive patients have an average survival of less than 1 year, whereas T (15; 17)-positive patients have a significantly better prognosis. Combining the methylation and mutation data reveals three distinct patient groups and four clusters of genes. We speculate that combined signatures have the better potential to be used for subclassification of AML, complementing cytogenetic signatures. A larger sample cohort and further investigation of the effects observed in this study are required to enable the clinical application of our patient classification aided by DNA methylation.
    Matched MeSH terms: Leukemia, Myeloid, Acute
  20. Survival and prognostic factors in Malaysian acute myeloid leukemia patients after allogeneic haematopoietic stem cell transplantation
    Mangantig E, Naing NN, Norsa'adah B, Azlan H
    Int J Hematol, 2013 Aug;98(2):197-205.
    PMID: 23719676 DOI: 10.1007/s12185-013-1373-1
    Studies of survival outcomes in acute myeloid leukemia (AML) patients treated with allogeneic haematopoietic stem cell transplantation (HSCT) are essential for planning patient care. The objectives of the present study were to determine overall survival (OS) and disease-free survival (DFS) in AML patients treated with allogeneic HSCT, and to identify prognostic factors associated with poor outcome. This study was conducted retrospectively, using data from the Blood and Bone Marrow Transplant, National Transplant Registry, Malaysia. All cases of AML treated with allogeneic HSCT registered at the registry between 1st January 1987 and 31st December 2010 were included in the study. A total of 300 patients were included for final analysis. The Kaplan-Meier method and Cox proportional hazard regression were used for statistical analysis. The overall 10-year OS and DFS for Malaysian AML patients after allogeneic HSCT were 63 and 67 %, respectively. Donor gender, marrow status, and conditioning intensity were identified as important prognostic factors for overall survival, whereas the significant prognostic factors for disease-free survival were ethnic group, donor gender, marrow status, and conditioning intensity. In conclusion, the survival outcomes for Malaysian AML patients treated with allogeneic HSCT were good, and this treatment should be considered the standard therapeutic approach for suitable candidates.
    Matched MeSH terms: Leukemia, Myeloid, Acute/mortality*; Leukemia, Myeloid, Acute/therapy*
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