Displaying publications 1 - 20 of 21 in total

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  1. Lum SH, Chin TF, Lau KH, Yap TY, Rajagopal R, Ariffin H
    Int J Hematol, 2014 Mar;99(3):215-6.
    PMID: 24470150 DOI: 10.1007/s12185-014-1515-0
  2. 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.
  3. Wahid SF
    Int J Hematol, 2013 May;97(5):581-98.
    PMID: 23585244 DOI: 10.1007/s12185-013-1313-0
    Hematopoietic stem cell transplantation (HCT) utilizing non-myeloablative (NMA) and reduced-intensity conditioning (RIC) regimens (collectively referred to as reduced-toxicity HCT, RT-HCT) has become a viable therapeutic option for patients with hematological malignancies who are ineligible for standard myeloablative conditioning transplantation (MA-HCT). RT-HCT has been shown to induce stable engraftment with low toxicity, and to produce similar overall and progression-free survival (PFS) when compared to MA-HCT in acute myeloid leukemia and myelodysplastic syndrome. The best results for RT-HCT have been reported for patients with disease that is in remission, indolent and chemosensitive, and with a strong graft-versus-malignancy effect. Chronic graft-versus-host disease seems to correlate with a lower relapse rate and better PFS. RT-HCT is inferior when performed in poor risk or advanced disease, due to high relapse rates. A search for novel strategies that includes the most appropriate conditioning regimens and post-transplant immunomodulation protocols with more intensive anti-malignancy activity but limited toxicity is in progress. This review provides an update on the results of clinical studies of RT-HCT, and discusses possible indications and investigative strategies for improving the clinical outcomes of RT-HCT for the major hematological malignancies.
  4. Nadarajan VS, Phan CL, Ang CH, Liang KL, Gan GG, Bee PC, et al.
    Int J Hematol, 2011 Apr;93(4):465-473.
    PMID: 21387093 DOI: 10.1007/s12185-011-0796-9
    The outcome of treating chronic myeloid leukemia (CML) with imatinib mesylate (IM) is inferior when therapy is commenced in late chronic or accelerated phase as compared to early chronic phase. This may be attributed to additional genomic alterations that accumulate during disease progression. We sought to identify such lesions in patients showing suboptimal response to IM by performing array-CGH analysis on 39 sequential samples from 15 CML patients. Seventy-four cumulative copy number alterations (CNAs) consisting of 35 losses and 39 gains were identified. Alterations flanking the ABL1 and BCR genes on chromosomes 9 and 22, respectively, were the most common identified lesions with 5 patients losing variable portions of 9q34.11 proximal to ABL1. Losses involving 1p36, 5q31, 17q25, Y and gains of 3q21, 8q24, 22q11, Xp11 were among other recurrent lesions identified. Aberrations were also observed in individual patients, involving regions containing known leukemia-associated genes; CDKN2A/2B, IKZF1, RB1, TLX1, AFF4. CML patients in late stages of their disease, harbor pre-existing and evolving sub-microscopic CNAs that may influence disease progression and IM response.
  5. Bee PC, Gan GG, Nadarajan VS, Latiff NA, Menaka N
    Int J Hematol, 2010 Jan;91(1):136-9.
    PMID: 20047097 DOI: 10.1007/s12185-009-0471-6
    The co-occurrence of JAK2 V617F mutation with BCR-ABL reciprocal translocation is uncommon. We report a 60-year-old man who initially presented with phenotype of polycythemia vera (PV), which evolved into chronic myeloid leukemia and back to PV once treatment with imatinib was commenced. JAK2 V617F mutation and BCR-ABL fusion transcripts were detected in the initial sample. However, JAK2 V617F alleles diminished when BCR-ABL mRNA burden increased and reappeared once the patient was commenced on imatinib. The dynamic interaction between JAK2 V617F and BCR-ABL implies that two independent clones exist with the JAK2 V617F clone only achieving clonal dominance when BCR-ABL positive clones are suppressed by imatinib.
  6. Yusoff NM, Shirakawa T, Nishiyama K, Ghazali S, Ee CK, Orita A, et al.
    Int J Hematol, 2002 Aug;76(2):149-52.
    PMID: 12215013 DOI: 10.1007/BF02982577
    Multiplex polymerase chain reaction (PCR) using multiple tandem forward primers and a common reverse primer (MPTP) was recently established as a comprehensive screening method for mutations in X-linked recessive diseases. In the work reported here, MPTP was used to scan for mutations of the glucose-6-phosphate dehydrogenase (G6PD) gene. Mutations in exons 3,4,5,6,7,9, 11, and 12 of the G6PD gene were screened by MPTP in 93 unrelated Malaysian patients with G6PD deficiency. Of the 93 patients, 80 (86%) had identified mutations. Although all of these were missense mutations, identified nucleotide changes were heterogeneous, with 9 mutations involving various parts of the exons. These 9 mutations were G-to-A nucleotide changes at nucleotide 871 of the G6PD gene (G871A), corresponding to G6PD Viangchan, G6PD Mediterranean (C563T), G6PD Vanua Lava (T383C), G6PD Coimbra (C592T), G6PD Kaiping (G1388A), G6PD Orissa (C131G), G6PD Mahidol (G487A), G6PD Canton (G1376T), and G6PD Chatham (G1003A). Our results document heterogeneous mutations of the G6PD gene in the Malaysian population.
  7. Masaoka T, Hiraoka A, Okamoto S, Kodera Y, Cao LX, Lu DP, et al.
    Int J Hematol, 1999 Oct;70(3):190-2.
    PMID: 10561913
    The first cooperative study of the Asian Pacific bone marrow transplantation group included 75 patients with early leukemia who received human leukocyte antigen-matched sibling bone marrow transplants and were randomized into granulocyte colony-stimulating factor and control groups. The selected patients were registered from 10 centers in six countries and areas within Asia (Beijing, Taipei, Hong Kong, Japan, Korea, and Malaysia). The incidence of grades II-IV acute graft-vs.-host disease was 22.2%, and the 2-year survival rate was 62.7%. The period of protective isolation (27.1-66.7 days), period of hospitalization (38.6-130.5 days), and medical costs for 4 months (US $10,300-US $80,803) varied considerably. Good cooperation, i.e., low rate of protocol violation or rapid and precise presentation of case reports, was obtained.
  8. Gan GG, Teh A, Goh KY, Chong HT, Pang KW
    Int J Hematol, 2003 Jul;78(1):84-6.
    PMID: 12894858
    Warfarin is a drug commonly used in the prevention of thromboembolic events. There have been reports suggesting that racial background may influence warfarin dose requirements. Malaysia is a multiracial country in which there are 3 major races, Malay, Chinese, and Indian. We examined 100 patients from our hospital on stable maintenance doses of warfarin, with international normalized ratio (INR) of 2.0 to 3.5. We found that the mean warfarin dose for Indian patients (n = 19) was 6.9 mg, for Chinese patients (n = 55) was 3.6 mg, and for Malay patients (n = 26) was 3.2 mg. The results showed that the Indian patients required a statistically significantly higher warfarin dose than did patients of the other 2 races (P < .0005). Age was also found to affect the daily warfarin maintenance dose.
  9. Jackson N, Hamizah I
    Int J Hematol, 1996 Dec;65(1):85-8.
    PMID: 8990629
    A 25-year-old lady presented with a severe normocytic anemia (Hb 5.3 g/dl) and a sideroblastic marrow at the end of her first pregnancy. Six months into the puerperium, after the transfusion of a total of 8 units of red cells, there was apparent spontaneous improvement and then she was lost to follow-up. After a second pregnancy without clinical problems, she presented during a third pregnancy, at the age of 30 years, with similar hematological findings. Twenty-two months later she was well with a normal blood count. One possible reason for relapse in pregnancy is the increased demand for pyridoxine that occurs, but only one other case of sideroblastic anemia relapsing during pregnancies has been reported.
  10. Bee PC, Gan GG, Sangkar JV, Teh A, Goh KY
    Int J Hematol, 2004 May;79(4):358-60.
    PMID: 15218965
    We diagnosed T-cell acute lymphoblastic leukemia (T-ALL) with multiple cytogenetic abnormalities in a 17-year-old girl a year after she had received a diagnosis of acute promyelocytic leukemia (APML). After the diagnosis of APML in June 2001, the patient was treated with idarubicin and all-trans-retinoic acid. In September 1999, her younger sister also received a diagnosis of APML and to date has remained well. T-ALL after remission of APML is very rare, and only 1 such case has been reported. Possible causes include therapy-related reasons, genetic susceptibility to leukemia, and environmental exposure.
  11. Che Yaacob NS, Islam MA, Alsaleh H, Ibrahim IK, Hassan R
    Int J Hematol, 2020 Mar;111(3):352-359.
    PMID: 31894534 DOI: 10.1007/s12185-019-02806-8
    Hemoglobin (Hb) is an iron-containing metalloprotein that transports oxygen molecules from the lungs to the rest of the human body. Among the different variants of Hb, HbA1 is the most common and is composed of two alpha (αHb) and two beta globin chains (βHb) constructing a heterotetrameric protein complex (α2β2). Due to the higher number of AHSP genes, there is a tendency to produce approximately twice as much of α subunit as β subunit. Therefore, there is a chance of presenting excess α subunit leftover in human blood plasma; excess subunits subsequently bind with each other and aggregates β-thalassemia occurs due to lack of or reduced numbers of βHb subunit. Alpha-hemoglobin-stabilizing protein (AHSP) is a scavenger protein which acts as a molecular chaperon by reversibly binding with free αHb forming a complex (AHSP-αHb) that prevents aggregation and precipitation preventing deleterious effects towards developing serious human diseases including β-thalassemia. Clinical severity worsens if mutations in AHSP gene co-occur in patients with β-thalassemia. Considering the mechanism of action of AHSP and its contribution to ameliorating β-thalassemia severity, it could potentially be used as a modulatory agent in the treatment of β-thalassemia.
  12. Kuan JW, Su AT, Tay SP, Fong IL, Kubota S, Su'ut L, et al.
    Int J Hematol, 2020 Feb;111(2):217-224.
    PMID: 31707540 DOI: 10.1007/s12185-019-02768-x
    The BCR-ABL1 fusion gene is the driver mutation of Philadelphia chromosome-positive chronic myeloid leukemia (CML). Its expression level in CML patients is monitored by a real-time quantitative polymerase chain reaction defined by the International Scale (qPCRIS). BCR-ABL1 has also been found in asymptomatic normal individuals using a non-qPCRIS method. In the present study, we examined the prevalence of BCR-ABL1 in a normal population in southern Sarawak by performing qPCRIS for BCR-ABL1 with ABL1 as an internal control on total white blood cells, using an unbiased sampling method. While 146 of 190 (76.8%) or 102 of 190 (53.7%) samples showed sufficient amplification of the ABL1 gene at > 20,000 or > 100,000 copy numbers, respectively, in qPCRIS, one of the 190 samples showed amplification of BCR-ABL1 with positive qPCRIS of 0.0023% and 0.0032% in two independent experiments, the sequence of which was the BCR-ABL1 e13a2 transcript. Thus, we herein demonstrated that the BCR-ABL1 fusion gene is expected to be present in approximately 0.5-1% of normal individuals in southern Sarawak.
  13. Lee YP, Yoon SE, Song Y, Kim SJ, Yoon DH, Chen TY, et al.
    Int J Hematol, 2021 Sep;114(3):355-362.
    PMID: 34302593 DOI: 10.1007/s12185-021-03179-7
    Cutaneous T-cell lymphomas (CTCLs) are a group of T-cell lymphomas with low incidence. Due to their indolent characteristics, treatment strategies have not yet been established for advanced CTCLs. In this study, relative incidence of CTCLs in Asia was estimated and the therapeutic outcomes presented based on various treatments currently used in clinics for advanced CTCLs. As part of a prospective registry study of peripheral T-cell lymphoma (PTCL) conducted across Asia, including Korea, China, Taiwan, Singapore, Malaysia, and Indonesia, subgroup analysis was performed for patients with CTCLs. Among 486 patients with PTCL, 37 with CTCL (7.6%) were identified between April 2016 and February 2019. Primary cutaneous ALK-negative anaplastic large cell lymphoma (ALCL, 35.1%) was the most common subtype. With a median follow-up period of 32.1 months, median progression-free survival (PFS) was 53.5 months (95% CI 0.0-122.5), and overall survival was not reached. 14 patients (48.2%) underwent subsequent treatment after the first relapse, but the response rate was 20% with a PFS of 2.2 months (95% CI 0.3-4.0). Six patients received autologous stem cell transplantation (auto-SCT). However, auto-SCT did not result in better outcomes. Additional studies are needed on standard care treatment of advanced or refractory and relapsed CTCLs.
  14. Chuncharunee S, Wong R, Rojnuckarin P, Chang CS, Chang KM, Lu MY, et al.
    Int J Hematol, 2016 Oct;104(4):454-61.
    PMID: 27376944 DOI: 10.1007/s12185-016-2053-8
    Due to the unavailability of horse antithymocyte globulin (ATG) in many markets worldwide, patients with severe aplastic anemia (SAA) are limited to the use of rabbit ATG. We aimed to analyze hematologic response and overall survival (OS) of Asian patients treated with rabbit ATG as first-line therapy of SAA. We retrospectively reviewed the medical records of 97 consecutive patients who received rabbit ATG as first-line treatment of SAA from 2006 to 2012 at centers in four Asian countries. The primary endpoint was 6- and 12-month overall response rates (ORR) for patients receiving rabbit ATG within the recommended dose range (2.5-3.75 mg/kg/day). Secondary endpoints included ORR in patients receiving any dose of rabbit ATG and 2-year OS. For patients who received rabbit ATG within the recommended dose range, 6- and 12-month ORRs were 17.4 and 63.6 %, respectively. For patients who received any dose of rabbit ATG, 6- and 12-month ORRs were 24.3 and 68.6 %, respectively. The 2-year OS rate was 86.3 %. Rabbit ATG is effective for treatment of SAA in Asian patients. The 12-month ORR and 2-year OS with rabbit ATG were comparable to historical results obtained with horse ATG.
  15. Kuan JW, Su AT, Leong CF, Osato M, Sashida G
    Int J Hematol, 2019 Jan;109(1):130.
    PMID: 30406326 DOI: 10.1007/s12185-018-2556-6
    The author would like to correct the error in the publication of the original article. The corrected detail is given below for your reading.
  16. Kotaki R, Higuchi H, Ogiya D, Katahira Y, Kurosaki N, Yukihira N, et al.
    Int J Hematol, 2017 Dec;106(6):811-819.
    PMID: 28831750 DOI: 10.1007/s12185-017-2314-1
    miR-1 and miR-133 are clustered on the same chromosomal loci and are transcribed together as a single transcript that is positively regulated by ecotropic virus integration site-1 (EVI1). Previously, we described how miR-133 has anti-tumorigenic potential through repression of EVI1 expression. It has also been reported that miR-1 is oncogenic in the case of acute myeloid leukemia (AML). Here, we show that expression of miR-1 and miR-133, which have distinct functions, is differentially regulated between AML cell lines. Interestingly, the expression of miR-1 and EVI1, which binds to the promoter of the miR-1/miR-133 cluster, is correlative. The expression levels of TDP-43, an RNA-binding protein that has been reported to increase the expression, but inhibits the activity, of miR-1, were not correlated with expression levels of miR-1 in AML cells. Taken together, our observations raise the possibility that the balance of polycistronic miRNAs is regulated post-transcriptionally in a hierarchical manner possibly involving EVI1, suggesting that the deregulation of this balance may play some role in AML cells with high EVI1 expression.
  17. Heng LL, Caguioa P, Chin NS, Chiou TJ, Lee JW, Miyakawa Y, et al.
    Int J Hematol, 2011 Aug;94(2):142-149.
    PMID: 21766185 DOI: 10.1007/s12185-011-0894-8
    Patients with primary immune thrombocytopenia (ITP) from the Asia-Pacific region often exhibit characteristics distinct from those of patients from the West. Moreover, as the region itself is heterogeneous, the ITP landscape among individual Asia-Pacific countries can be diverse. The recently released international consensus report on ITP places new emphasis on ITP, but does not address the unique ITP landscape in the Asia-Pacific region, which is home to 60% of the world's population. In an attempt to characterize how the ITP landscape differs between the West and the Asia-Pacific region, an expert panel with representatives from Northeast Asia, Southeast Asia, and Australia was convened. Important differences were identified between the guidance provided in the international consensus report and experience in the Asia-Pacific region, namely diagnostic practices, incidence and approach to ITP secondary to H. pylori infection, systemic lupus erythematosus-related ITP, the use of bone marrow examination, initial treatment strategies, and the role of splenectomy, rituximab, and thrombopoietin receptor agonists.
  18. Viprakasit V, Ibrahim H, Ha SY, Ho PJ, Li CK, Chan LL, et al.
    Int J Hematol, 2011 Mar;93(3):319-328.
    PMID: 21374076 DOI: 10.1007/s12185-011-0789-8
    Although thalassaemia is highly prevalent in the Asia-Pacific region, clinical data on efficacy and safety profiles of deferasirox in patients from this region are rather limited. Recently, data from the multicentre Evaluation of Patients' Iron Chelation with Exjade (EPIC) study in 1744 patients with different anaemias has provided an opportunity to analyse 1115 thalassaemia patients, of whom 444 patients were from five countries in the Asia-Pacific region (AP) for whom thalassaemia management and choice of iron chelators were similar. Compared to the rest of the world (ROW), baseline clinical data showed that the AP group appeared to be more loaded with iron (3745.0 vs. 2822.0 ng/ml) and had a higher proportion on deferoxamine monotherapy prior to the study (82.9 vs. 58.9%). Using a starting deferasirox dose based on transfusional iron intake and tailoring it to individual patient response, clinical efficacy based on serum ferritin reduction in AP and ROW thalassaemia patients was similar. Interestingly, the AP group developed a higher incidence of drug-related skin rash compared to ROW (18.0 vs. 7.2%), which may indicate different pharmacogenetic backgrounds in the two populations. Our analysis confirms that, with appropriate adjustment of dose, deferasirox can be clinically effective across different regions, with manageable side effects.
  19. Viprakasit V, Lee-Lee C, Chong QT, Lin KH, Khuhapinant A
    Int J Hematol, 2009 Nov;90(4):435-445.
    PMID: 19862602 DOI: 10.1007/s12185-009-0432-0
    Worldwide, thalassemia is the most commonly inherited hemolytic anemia, and it is most prevalent in Asia and the Middle East. Iron overload represents a significant problem in patients with transfusion-dependent beta-thalassemia. Chelation therapy with deferoxamine has traditionally been the standard therapeutic option but its usage is tempered by suboptimal patient compliance due to the discomfort and demands associated with the administration regimen. Therefore, a great deal of attention has been focused on the development of oral chelating agents. Deferiprone, even though available for nearly two decades in Asia with recent encouraging data on cardiac iron removal and long-term efficacy, has serious adverse effects including agranulocytosis and neutropenia which has impeded it from routine clinical practice. A novel oral chelator; deferasirox is effective throughout a 24 h dosing period and both preclinical and clinical data indicate that it successfully removes both hepatic and cardiac iron. In Asia, optimal management of severe thalassemia patients and the availability and access to oral iron chelators still presents a major challenge in many countries. In this regard, the development and implementation of consensus guidelines for management of Asian patients with transfusion-dependent thalassemia will be a major step towards improving and maintaining the continuity of patient care.
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