exudates and Leukemia--Myelogenous--Chronic--BCR-ABL-Positive

The burden of chronic myeloid leukaemia (CML) is increasing due to longer patient survival, better life expectancy of the general population, and increasing drug prices. Funding is one of the main concerns in the choice of CML medication used worldwide; thus, patient assistance programmes were introduced to ensure accessibility to affordable treatment. In this study, we evaluated CML drug distribution inequality in Malaysia through patient assistance programmes, using pharmaco-economics methods to evaluate CML treatment from the care provider's perspective.. Patients with CML were recruited from outpatient haematological clinics at the national centre of intervention and referral for haematological conditions and a public teaching hospital. The health-related quality of life or utility scores were derived using the EuroQol EQ-5D-5L questionnaire. Costing data were obtained from the Ministry of Health Malaysia Casemix MalaysianDRG. Imatinib and nilotinib drug costs were obtained from the administration of the participating hospitals and pharmaceutical company.. Of the 221 respondents in this study, 68.8% were imatinib users. The total care provider cost for CML treatment was USD23,014.40 for imatinib and USD43,442.69 for nilotinib. The governmental financial assistance programme reduced the total care provider cost to USD13,693.51 for imatinib and USD19,193.45 for nilotinib. The quality-adjusted life years (QALYs) were 17.87 and 20.91 per imatinib and nilotinib user, respectively. Nilotinib had a higher drug cost than imatinib, yet its users had better life expectancy, utility score, and QALYs. Imatinib yielded the lowest cost per QALYs at USD766.29.. Overall, imatinib is more cost-effective than nilotinib for treating CML in Malaysia from the care provider's perspective. The findings demonstrate the importance of cancer drug funding assistance for ensuring that the appropriate treatments are accessible and affordable and that patients with cancer use and benefit from such patient assistance programmes. To establish effective health expenditure, drug distribution inequality should be addressed.

Topics: Antineoplastic Agents; Chronic Disease; Cost-Benefit Analysis; Dasatinib; Drug Utilization; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Malaysia; Protein Kinase Inhibitors; Pyrimidines; Quality of Life

Background Tyrosine kinase inhibitors have been demonstrated to improve the survival of patients with chronic myeloid leukaemia. However, medication adherence is vital for patients on chronic treatment. Objective The objective of the current study was to evaluate response to treatment, adherence by patients to tyrosine kinase inhibitors and factors associated with adherence and response. Setting A haematology clinic in a regional referral hospital in Malaysia. Method Patients aged ≥ 13 years who had been on imatinib or nilotinib for ≥ 12 months were included in this cross-sectional study. An optimal response was defined as the achievement of major molecular response at 12 months of treatment. Patient medication adherence was determined using the average medication possession ratio based on the dispensing records. The patients were considered adherent if the medication possession ratio was > 90%. Multiple logistic regression was performed to evaluate the factors associated with adherence. The association of adherence with molecular response was analysed by univariate logistic regression. Main outcome measure The primary outcome measures were the proportion of patients who achieved optimal response and the medication possession ratio. Results A total of 151 patients were screened, and 71 patients were included. Twenty-eight patients (39%) achieved major molecular response at 12 months of treatment. The median time to achieve this was 15.5 months (an interquartile range of 15). The mean medication possession ratio for imatinib and nilotinib was 0.94 (± 0.14) and 0.96 (± 0.10), respectively, but this difference was without statistical significance (t  =  - 0.517, p  =  0.610). Nausea and vomiting (odds ratio [OR] of 0.25, 95% confidence interval [CI]: 0.07-0.83, p  =  0.023) and disease phase at diagnosis (OR of 0.20, 95% CI 0.04-1.06, p  =  0.059) were associated with patient adherence. An association was not found between patient adherence and molecular response (OR of 1.03, 95% CI 0.35-3.09, p  =  0.956). Conclusion The patients in this study demonstrated a relatively deep molecular response and optimal adherence. Nevertheless, one fourth of them were noncompliant with imatinib. Therefore, active interventions are warranted to prevent treatment-associated adverse events and improve adherence.

Topics: Adult; Aged; Antineoplastic Agents; Cross-Sectional Studies; Hospitals; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Malaysia; Medication Adherence; Protein Kinase Inhibitors; Treatment Outcome

The FAS mediated apoptosis pathway involving the FAS and FASL genes plays a crucial role in the regulation of apoptotic cell death and imatinib mesylate (IM) mechanism of action. Promoter polymorphisms FAS-670 A>G and FAS-844 T>C which alter the transcriptional activity of these genes may grant a risk to develop cancer and revamp the drug activities towards the cancer cell. We investigated the association of these two polymorphisms with the susceptibility risk and IM treatment response in Malaysian chronic myeloid leukaemia (CML) patients.. This is a retrospective study, which included 93 CML patients and 98 controls. The polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method was used to genotype the FAS and FASL polymorphisms. Data nanlysis was done using SPSS Version 22. The associations of the genotypes with susceptibility risk and IM response in CML patients were assessed by means of logistic regression analysis and deriving odds ratio with 95% CI.. We observed a significant association between FASL-844T>C polymorphism and CML susceptibility risk and IM response. Variant C allele and FASL-844 CC variant genotype carriers had significantly higher risk for CML susceptibility (OR 1.756, CI 1.163-2.652, p=0.007 and OR 2.261, CI 1.013-5.047, p=0.047 respectively). Conversely, the heterozygous genotype FASL-844 TC conferred lower risk for CML susceptibility (OR 0.379, CI 0.176-0.816, p=0.013). The heterozygous and homozygous variant genotypes and variant C alleles were found to confer a lower risk for the development of IM resistance with OR 0.129 (95% CI: 0.034-0.489 p=0.003), OR 0.257 (95% CI: 0.081-0.818, p=0.021), and OR 0.486 (95% CI: 0.262-0.899, p=0.021) respectively. We also found that FAS-670 A>G polymorphism was not associated with CML susceptibility risk or IM response.. The genetic polymorphism FASL-844 T>C may contribute to the CML susceptibility risk and also IM treatment response in CML patients. Accodringly, it may be useful as a biomarker for predicting CML susceptibility risk and IM resistance.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Child; Fas Ligand Protein; Female; Genetic Predisposition to Disease; Genotype; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Logistic Models; Malaysia; Male; Middle Aged; Polymorphism, Genetic; Promoter Regions, Genetic; Retrospective Studies; Young Adult

There are very few published chronic myeloid leukaemia (CML) epidemiology studies in South-East Asia and no representative from Malaysia.. This is a cross-sectional study of adult CML patients (citizen) in a single but representative centre in southern Sarawak.. Total 79 patients (Malay 39%, Chinese 30.4%, Iban 17.7%, Bidayuh 12.7%) were identified from the databases. Median age at diagnosis was younger, 40, compared to developed countries due to population structure. M:F ratio was higher, 2.6:1 compared to other countries 1.3-1.7:1. Majority presented at chronic phase (89.5%), low/intermediate risk score (80%) and started imatinib (96%) as first line tyrosine kinase inhibitor (TKI), which 40% of them switched to other TKI due to intolerance (17%) and failure (including disease progression)/not achieving major molecular response (83%). Quantitative polymerase chain reaction (qPCR) assessment after three months of TKI treatment had higher positive predictive value to predict Imatinib failure, 75%, than qPCR assessment after six months of TKI treatment, 58%. Presenting phase, symptoms, signs and laboratory data were like most countries. Estimated prevalence and incidence of CML in southern Sarawak was 69.2/1,000,000 population at the Year 2016 (similar to most developing countries) and 8.0/1,000,000 population per year at the Year 2011-2016 (similar to most countries), respectively. The incidence increased with age and was lowest among Iban, 12.8 and highest among Chinese, 19.5, which was 4x higher than Chinese in China. The prevalence of different BCR-ABL1 transcript type was like other Asia countries CONCLUSION: Significant epidemiological differences on M:F ratio and ethnic groups compared to other countries warrant further study.

Topics: Adolescent; Adult; Age Factors; Aged; Child; Cross-Sectional Studies; Female; Humans; Incidence; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Malaysia; Male; Middle Aged; Prevalence; Risk Factors; Sex Factors; Young Adult

Objective: Chronic Myeloid Leukemia (CML) is caused by a reciprocal translocation between chromosomes 9\ and 22, t(9;22) (q34;q11) which encodes for the BCR-ABL fusion protein. Discovery of Imatinib Mesylate (IM) as\ first line therapy has brought tremendous improvement in the management of CML. However, emergence of point\ mutations within the BCR-ABL gene particularly T315I mutation, affects a common BCR-ABL kinase contact residue\ which impairs drug binding thus contribute to treatment resistance. This study aims to investigate the BCR-ABL T315I\ mutation in Malaysian patients with CML. Methods: A total of 285 patients diagnosed with CML were included in this\ study. Mutation detection was performed using qualitative real-time PCR (qPCR). Results: Fifteen out of 285 samples\ (5.26%) were positive for T315I mutations after amplification with real-time PCR assay. From the total number of\ positive samples, six patients were in accelerated phase (AP), four in chronic phase (CP) and five in blast crisis (BC).\ Conclusion: Mutation testing is recommended for choosing various tyrosine kinase inhibitors (TKIs) to optimize\ outcomes for both cases of treatment failure or suboptimal response to imatinib. Therefore, detection of T315I mutation\ in CML patients are clinically useful in the selection of appropriate treatment strategies to prevent disease progression.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Child; Child, Preschool; Drug Resistance, Neoplasm; Female; Fusion Proteins, bcr-abl; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Malaysia; Male; Middle Aged; Mutation; Prevalence; Protein Kinase Inhibitors; Young Adult

Clinical resistance to imatinib (IM) in chronic myeloid leukemia (CML) carries adverse consequences. We investigated 22 CML patients who developed IM-resistance for BCR-ABL kinase domain (KD) mutations. The median follow-up for this study was 101.9 months (range: 22.2 to 176.5 months) and the estimated mean overall survival was 150.87 months (95% CI: 130.0 to 171.0). Five out of 22 patients tested positive for BCR-ABL KD mutations: 2 had T315I, 2 had E255K and 1 had V289F mutations. Of the remaining 17 patients who did not harbor BCR-ABL KD mutations, 11 patients received nilotinib while the rest continued on IM. All 17 achieved haematological remission but only 5 patients achieved complete cytogenetic remission, 4 of whom did so after switching to nilotinib. Our study shows that most of our IM-resistant patients do not test positive for BCR-ABL KD mutations by available testing methods and the role of second generation tyrosine kinase inhibitors remains undetermined. A critical analysis of the BCR-ABL KD mutations and the underlying mechanisms/ pathways of BCR-ABL independent IM-resistance along with potential treatments in the horizon will be discussed.

Topics: Adult; Aged; Antineoplastic Agents; Developing Countries; Drug Resistance, Neoplasm; Female; Fusion Proteins, bcr-abl; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Malaysia; Male; Middle Aged; Mutation; Retrospective Studies

The detoxifying activity of glutathione S-transferases (GST) enzymes not only protect cells from the adverse effects of xenobiotics, but also alters the effectiveness of drugs in cancer cells, resulting in toxicity or drug resistance. In this study, we aimed to evaluate the association of GSTM1, GSTT1 and GSTP1 Ile105Val polymorphisms with treatment response among Malaysian chronic myeloid leukaemia (CML) patients who everyday undergo 400 mg of imatinib mesylate (IM) therapy. Multiplex polymerase chain reaction (multiplex-PCR) was performed to detect GSTM1 and GSTT1 polymorphisms simultaneously and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was conducted to detect the GSTP1 Ile195Val polymorphism. On evaluating the association of the variant genotype with treatment outcome, heterozygous variant (AG) and homozygous variant (GG) of GSTP1 Ile105Val showed significantly a higher risk for the development of resistance to IM with OR: 1.951 (95% CI: 1.186-3.209, P = 0.009) and OR: 3.540 (95% CI: 1.305-9.606, P = 0.013), respectively. Likewise, GSTT1 null genotype was also associated with a significantly higher risk for the development of resistance to IM with OR = 1.664 (95% CI: 1.011-2.739, P = 0.045). Our results indicate the potential usefulness of GST polymorphism genotyping in predicting the IM treatment response among CML patients.

Topics: Alleles; Amino Acid Substitution; Antineoplastic Agents; Female; Genotype; Glutathione S-Transferase pi; Glutathione Transferase; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Malaysia; Male; Odds Ratio; Pharmacogenomic Variants; Polymorphism, Single Nucleotide; Protein Kinase Inhibitors; Treatment Outcome

The prognosis of patients with chronic myeloid leukaemia (CML) has improved since the introduction of imatinib. However, patients who do not achieve complete cytogenetic response (CCyR) and major molecular response (MMR) have poorer prognosis. Recent clinical trials have demonstrated that early and deeper cytogenetic and molecular responses predict a better long-term outcome. This study aimed to analyse the relationship between early molecular response and clinical outcome in a real-life setting.. This retrospective study included all patients with CML, in chronic or accelerated phase, who were treated with imatinib at University of Malaya Medical Centre, Malaysia.. A total of 70 patients were analysed. The median follow-up duration was 74 months, and the cumulative percentages of patients with CCyR and MMR were 80.0% and 65.7%, respectively. Overall survival (OS) and event-free survival (EFS) at ten years were 94.3% and 92.9%, respectively. Patients who achieved CCyR and MMR had significantly better OS and EFS than those who did not. At six months, patients who had a BCR-ABL level ≤ 10% had significantly better OS and EFS than those who had a BCR-ABL level > 10%. The target milestone of CCyR at 12 months and MMR at 18 months showed no survival advantage in our patients.. Our data showed that imatinib is still useful as first-line therapy. However, vigilant monitoring of patients who have a BCR-ABL level > 10% at six months of treatment should be implemented so that prompt action can be taken to provide the best outcome for these patients.

Topics: Academic Medical Centers; Adult; Antineoplastic Agents; Cytogenetics; Disease-Free Survival; Female; Follow-Up Studies; Fusion Proteins, bcr-abl; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Malaysia; Male; Middle Aged; Predictive Value of Tests; Prognosis; Retrospective Studies; Treatment Outcome; Universities

Discovery of imatinib mesylate (IM) as the targeted BCR-ABL protein tyrosine kinase inhibitor (TKI) has resulted in its use as the frontline therapy for chronic myeloid leukemia (CML) across the world. Although high response rates are observed in CML patients who receive IM treatment, a significant number of patients develop resistance to IM. Resistance to IM in patients has been associated with a heterogeneous array of mechanisms of which point mutations within the ABL tyrosine kinase domain (TKD) are the frequently documented. The types and frequencies of mutations reported in different population studies have shown wide variability. We screened 125 Malaysian CML patients on IM therapy who showed either TKI refractory or resistance to IM to investigate the frequency and pattern of BCR-ABL kinase domain mutations among Malaysian CML patients undergoing IM therapy and to determine the clinical significance. Mutational screening using denaturing high performance liquid chromatography (dHPLC) followed by DNA sequencing was performed on 125 IM resistant Malaysian CML patients. Mutations were detected in 28 patients (22.4%). Fifteen different types of mutations (T315I, E255K, G250E, M351T, F359C, G251E, Y253H, V289F, E355G, N368S, L387M, H369R, A397P, E355A, D276G), including 2 novel mutations were identified, with T315I as the predominant type of mutation. The data generated from clinical and molecular parameters studied were correlated with the survival of CML patients. Patients with Y253H, M351T and E355G TKD mutations showed poorer prognosis compared to those without mutation. Interestingly, when the prognostic impact of the observed mutations was compared inter-individually, E355G and Y253H mutations were associated with more adverse prognosis and shorter survival (P=0.025 and 0.005 respectively) than T315I mutation. Results suggest that apart from those mutations occurring in the three crucial regions (catalytic domain, P-loop and activation-loop), other rare mutations also may have high impact in the development of resistance and adverse prognosis. Presence of mutations in different regions of BCR-ABL TKD leads to different levels of resistance and early detection of emerging mutant clones may help in decision making for alternative treatment. Serial monitoring of BCR-ABL1 transcripts in CML patients allows appropriate selection of CML patients for BCR-ABL1 KD mutation analysis associated with acquired TKI resistance. Identification of these KD mutatio

Topics: Adolescent; Adult; Aged; Asian People; Benzamides; Catalytic Domain; DNA Mutational Analysis; Drug Resistance, Neoplasm; Female; Fusion Proteins, bcr-abl; Gene Frequency; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Malaysia; Male; Middle Aged; Mutation, Missense; Piperazines; Prognosis; Protein Kinase Inhibitors; Pyrimidines; Survival Analysis; Young Adult

The introduction and success of imatinib mesylate (IM) has brought about a paradigm shift in chronic myeloid leukaemia (CML) treatment. However, despite the high efficacy of IM, clinical resistance develops due to a heterogeneous array of mechanisms. Pharmacogenetic variability as a result of genetic polymorphisms could be one of the most important factors influencing resistance to IM. The aim of this study was to investigate the association between genetic variations in drug efflux transporter ABCC1 (MRP1) and ABCC2 (MRP2) genes and response to IM in patients with CML.. We genotyped 215 Malaysian patients with CML (comprising of two groups with 108 IM resistant and 107 IM responsive) for polymorphisms of ABCC1 (2012G>T and 2168G>A) and ABCC2 (-24C>T, 1249G>A and 3972C>T) genes. Genotype, allele and haplotype frequencies were compared between two groups of patients. Patients with CML were further stratified according to their clinical response to IM into those having cytogenetics and molecular responses, and the associations with genotypes were evaluated.. We observed no significant differences in the distribution of any of the tested genotypes between the investigated groups. However, on evaluating the risk association, ABCC2 T₋₂₄ G₁₂₄₉ T₃₉₇₂ haplotype was found to be associated with IM resistance (P = 0·046). These results suggest that haplotype variants -24T and 3972T might be associated with lower expression of ABCC2 protein and reduced transport activity and hence might be contributing to development of IM resistance.. Our results suggest the ABCC2 T₋₂₄ G₁₂₄₉ T₃₉₇₂ haplotype was associated with imatinib resistance. However, the evidence is as yet insufficient to establish this haplotype as a predictive biomarker for response to the drug.

Topics: Adolescent; Adult; Aged; Alleles; Antineoplastic Agents; Asian People; Benzamides; Child; Cross-Sectional Studies; Drug Resistance, Neoplasm; Female; Genotype; Haplotypes; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Malaysia; Male; Middle Aged; Multidrug Resistance-Associated Protein 2; Multidrug Resistance-Associated Proteins; Pharmacogenetics; Piperazines; Polymorphism, Single Nucleotide; Pyrimidines; Young Adult

The introduction of imatinib mesylate in 1998 has changed the management of chronic myeloid leukaemia. It is now the first-line therapy for newly diagnosed chronic myeloid leukaemia patients worldwide. However, its long-term survival benefit still needs to be established in clinical setting among Asian patients.. All chronic myeloid leukaemia patients in the chronic phase who were on imatinib mesylate therapy were retrospectively reviewed. Data was collected through a review of case notes, which was then processed, managed and analysed.. A total of 44 patients were included in the study. The cumulative rates of complete haematological response, major cytogenetic response and major molecular response were 93.2%, 75.0% and 34.2%, respectively. The overall survival and event-free survival at five years were 86.0% and 84.9%, respectively. 31.8% of the patients developed anaemia, 29.5% neutropenia and 27.3% thrombocytopenia. A total of 43.2% of patients developed non-haematological side effects. Higher dosage (> 600 mg) and smaller body size (< 60 kg) were risk factors for haematological side effects. Patients with major cytogenetic response and absence of thrombocytopenia had better survival.. The majority of our chronic myeloid leukaemia patients did well with imatinib therapy. The adverse effects in our patients were tolerable, and no patient had to stop treatment permanently.

Topics: Academic Medical Centers; Adolescent; Adult; Aged; Antineoplastic Agents; Benzamides; Cytogenetics; Disease-Free Survival; Female; Hospitals, Teaching; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Malaysia; Male; Middle Aged; Piperazines; Pyrimidines; Treatment Outcome

This study aimed to explore the influence of SLC22A1, PXR, ABCG2, ABCB1 and CYP3A5 3 genetic polymorphisms on imatinib mesylate (IM) pharmacokinetics in Asian patients with chronic myeloid leukemia (CML).. Healthy subjects belonging to three Asian populations (Chinese, Malay, Indian; n = 70 each) and CML patients (n = 38) were enrolled in a prospective pharmacogenetics study. Imatinib trough (C(0h)) and clearance (CL) were determined in the patients at steady state. Haplowalk method was applied to infer the haplotypes and generalized linear model (GLM) to estimate haplotypic effects on IM pharmacokinetics. Association of haplotype copy numbers with IM pharmacokinetics was defined by Mann-Whitney U test.. Global haplotype score statistics revealed a SLC22A1 sub-haplotypic region encompassing three polymorphisms (rs3798168, rs628031 and IVS7+850C>T), to be significantly associated with IM clearance (p = 0.013). Haplotype-specific GLM estimated that the haplotypes AGT and CGC were both associated with 22% decrease in clearance compared to CAC [CL (10(-2) L/hr/mg): CAC vs AGT: 4.03 vs 3.16, p = 0.017; CAC vs CGC: 4.03 vs 3.15, p = 0.017]. Patients harboring 2 copies of AGT or CGC haplotypes had 33.4% lower clearance and 50% higher C(0h) than patients carrying 0 or 1 copy [CL (10(-2) L/hr/mg): 2.19 vs 3.29, p = 0.026; C(0h) (10(-6) 1/ml): 4.76 vs 3.17, p = 0.013, respectively]. Further subgroup analysis revealed SLC22A1 and ABCB1 haplotypic combinations to be significantly associated with clearance and C(0h) (p = 0.002 and 0.009, respectively).. This exploratory study suggests that SLC22A1-ABCB1 haplotypes may influence IM pharmacokinetics in Asian CML patients.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Asian People; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Benzamides; Female; Haplotypes; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Linkage Disequilibrium; Malaysia; Male; Middle Aged; Organic Cation Transporter 1; Pharmacogenetics; Piperazines; Polymorphism, Single Nucleotide; Protein Kinase Inhibitors; Pyrimidines; Treatment Outcome; Young Adult

Molecular pathogenesis of chronic myeloid leukemia (CML) is well established and molecular monitoring for patients with CML has become an important practice in the management of patients on imatinib therapy. In the present study, we report the use of RQ-PCR method for detection of BCR-ABL fusion gene for our CML cases. We performed a two-step RQ-PCR on bone marrow aspirates or peripheral blood of 37 CML patients. Quantitative expression of BCR-ABL fusion gene was carried out relative to the expression of a housekeeping gene as endogenous control to compensate for uneven cell numbers, RNA quality, or variations in reverse transcription efficiencies. Twenty-four of these patients were pre-treated with hydroxyurea or alpha interferon prior to the imatinib therapy. Their BCR-ABL fusion gene levels were monitored for 18 months. All samples processed were evaluable. The PCR amplification efficiency of the ABL gene is 90.5% (0.2158) and the BCR-ABL gene, 93.4% (0.1573).

Topics: Fusion Proteins, bcr-abl; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Malaysia; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction

This study was done to assess the overall response rate of imatinib mesylate in local patients with chronic myeloid leukaemia. A total of 69 patients were recruited with male/female ratio of 7:3. Of the 69 patients; 35% were in the chronic phase, 41% were in the accelerated phase, 17% were in blast crisis and the remaining 7% were after stem cell transplantation. Complete haematological response rates of patients in chronic phase, accelerated phase and blast crisis were 95.8%, 96.4% and 41.7% respectively. Thirty-eight percent of patients achieved complete cytogenetic response and 10% achieved partial cytogenetic response. The cytogenetic response rates were 80%, 41.7% and 18.2% in chronic, accelerated and blast crisis phase respectively (p < 0.005). Twenty-six percent of patients developed anaemia, 13% had neutropenia and 12% had thrombocytopenia after starting on treatment. In addition, 14% of patients developed peripheral oedema, 13% complained of musculoskeletal pain, 12% had gastrointestinal side effects which include nausea, vomiting and diarrhoea, 9% had grade 1 hepatotoxicity, 7% developed skin rashes and one patient had an abnormal renal function test. Patients taking 600mg or higher dosage of imatinib had more gastrointestinal side effects. Patients who weighed less than 60kg had a much higher risk of developing anaemia. Anaemia was a negative predictor of cytogenetic response. Presenting high white blood cell counts and absence of cytogenetic response were also negative predictors of survival. Overall survival was 87%. This was affected by the different phases of disease (chronic phase was better than accelerated and blast crisis) (p < 0.001). In conclusion, our local CML patients did well on treatment with imatinib.

Topics: Antineoplastic Agents; Benzamides; Cytogenetics; Disease Progression; Female; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Malaysia; Male; Piperazines; Prognosis; Prospective Studies; Pyrimidines; Treatment Outcome

Topics: Anemia, Aplastic; Benzamides; Chronic Disease; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Malaysia; Male; Middle Aged; Pancytopenia; Piperazines; Pyrimidines; Singapore; Time Factors

Rearrangements in the DNA of chronic myelogenous leukemia patients of Chinese, Malay and Indian origin were detected in the breakpoint cluster region of chromosome 22 using molecular techniques. The DNA of fifty patients was examined using a 1.2 kb DNA probe. Rearrangements were detected in 46/50 patients. Karyotypic data were available in nine patients, all of whom were Philadelphia chromosome positive and exhibited DNA rearrangement. Detection of the Philadelphia translocation by molecular methods, at this institution, where cytogenetics is not routinely performed, confirms its diagnostic value. The rearrangement data obtained in this study is consistent with molecular features of chronic myelogenous leukemia patients of Western countries.

Topics: Adolescent; Adult; Aged; Child; China; Chromosomes, Human, Pair 22; Female; Gene Rearrangement; Humans; India; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Malaysia; Male; Middle Aged; Philadelphia Chromosome; Translocation, Genetic