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  1. Fulltext Unrelated cord blood transplantation in children--a 10-year experience from UMMC
    Chan LL, Lin HP, Chong LA, Hany A, Ariffin AW
    Med J Malaysia, 2009 Jun;64(2):124-9.
    PMID: 20058571
    Children who would benefit from a haematopoietic stem cell transplantation often lacked a compatible sibling donor. Unrelated cord blood transplantation was offered as an alternative donor source for patients with a variety of malignant and non-malignant diseases who had no further treatment options. Cord blood units were sourced from various international cord blood registries. The median nucleated and CD34+ cell doses were 8.7 x 10(7)/kg and 2.6 x 10(5)/kg respectively. In spite of adequate cell doses, a high rate of non-engraftment of 32% was observed. Acute graft-versus-host disease (GVHD) occurred in 14 out of the 15 patients who engrafted with 53% being grade III to IV GVHD. The five year disease free survival was 40.7% with infection and GVHD being the commonest causes of death. The five year disease free survival was 20.5% and 60.7% for malignant and non-malignant diseases respectively.
  2. Fulltext Providing a cure for beta thalassaemia major
    Chan LL, Lin HP, Ariffin WA, Ariffin H
    Med J Malaysia, 2001 Dec;56(4):435-40.
    PMID: 12014762
    The current treatment options for beta thalassaemia major patients include conservative treatment with blood cell transfusions and iron chelation or stem cell transplantation. Regular blood transfusions inevitably lead to multi-organ haemosiderosis and are attended by risks of blood-borne infections. Results from stem cell transplantation are good and suggest that this should be offered as first line therapy when a matched sibling donor is available because the patient is often cured and able to live a normal life. Of 38 Malaysian children who underwent bone marrow or cord blood transplantations using matched sibling donors, 29 (76%) are now cured.
  3. 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.
  4. Screening for G. 6-P.D. deficiency
    Robinson MJ, Lau KS, Lin HP, Chan GL
    Med J Malaysia, 1976 Jun;30(4):287-90.
    PMID: 979730
  5. 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.
  6. Fulltext Presenting features and treatment outcome of 78 Malaysian children with neuroblastoma
    Ng SM, Abdullah WA, Lin HP, Chan LL
    Southeast Asian J. Trop. Med. Public Health, 1999 Mar;30(1):149-53.
    PMID: 10695803
    To study the distribution of presenting features and their prognostic significance in neuroblastoma treated in a single institution in Malaysia. A retrospective study was made of 78 neuroblastoma cases diagnosed and treated in the University Hospital, Kuala Lumpur, Malaysia between June 1982 and February 1997. Diagnosis was established by standard histological criteria. The presenting features were evaluated for their distribution and prognostic influence. Disease-free survival from diagnosis was the outcome variable of interest. The ages ranged from 0.1 to 11 years old (median: 3 years old). The tumor originated from the adrenal glands in 83% and the majority of cases presented in advanced stage (stage III 22%, stage IV 66%). Bone marrow was the commonest site of distant metastasis occurring in 45% of patients. The main presenting signs and symptoms in decreasing order were pallor, fever, abdominal mass, weight loss, and bone/joint pain. Univariate analysis conferred age, initial stage and Hb level as significant prognostic factors. No influence in disease-free survival was found for sex, race, primary site, urinary vanillylmandelic acid level, white cell count and platelet count. Overall 2-year disease-free survival was achieved in 27 (39%) patients. Four patients underwent bone marrow transplant, three of whom achieved 2-year disease-free survival. The results suggest that age, initial stage and hemoglobin level are significant prognostic factors based on univariate analysis. In addition, more Malaysian children presented with adrenal primary site and advanced disease compared to previous reported studies.
  7. Fulltext Concordant childhood acute lymphoblastic leukemia in monozygotic twins
    Chin YM, Wan Ariffin A, Lin HP, Chan YS
    Med J Malaysia, 1996 Mar;51(1):145-8.
    PMID: 10967997
    Two 4-year-old monozygotic Chinese, female twins developed concordant childhood acute lymphoblastic leukemia (ALL) within an interval of about 2 weeks. Based on morphology and cytochemistry findings of the bone marrow blast cells, a diagnosis of ALL, L1 was made. Immunophenotyping showed the blast cells of both twins expressed similar antigens, i.e. HLA-DR, CD10, CD13, CD19, CD22 and CD34. Identical blood group, same HLA (human leucocyte antigen) genotype, sex and similar appearance suggest that the twins are monozygotic. Since the bone marrow leukemic cells of both twins were identical in morphology and expressed the same antigens with almost similar percentages of positivity, it is likely that the blast cells were derived from the same single clone. Based on the single clone hypothesis, the leukemogenic event must have arisen in utero in one twin and the cells from the abnormal clone then spread to the other twin via shared placental anastomoses.
  8. Viva-Asia Blood and Marrow Transplantation Groups - A Survey of Consortium Activity over a 12-year Period (2000 to 2011)
    Tan AM, Ha C, Li CF, Chan GC, Lee V, Tan PL, et al.
    Ann Acad Med Singap, 2016 Mar;45(3):106-9.
    PMID: 27146463
  9. Clinical features and treatment outcome of children with myeloid antigen coexpression in B-lineage acute lymphoblastic leukemia: a study of 151 Malaysian children
    Ng SM, Ariffin WA, Lin HP, Chan LL, Chin YM
    J Trop Pediatr, 2000 Apr;46(2):73-8.
    PMID: 10822932
    The purpose of the study was to evaluate the incidence of myeloid antigen coexpression and its prognostic significance in childhood acute lymphoblastic leukemia (ALL) in Malaysia. A retrospective study was conducted of all ALL cases (< or = 12 years old) diagnosed and treated in University Hospital, Kuala Lumpur, Malaysia between 1 January 1992 and 30 May 1995, with available immunophenotype data. Presenting features and treatment outcome of 39 B-lineage ALL patients with myeloid antigen coexpression (My+B) were compared with 112 B-lineage ALL patients without myeloid antigen coexpression (My-B) for similarity in demographic, clinical and laboratory features and their treatment outcome. My+B and My-B patients were treated with a uniform treatment protocol. Myeloid antigen coexpression was defined as more than 30% isolated leukemic cells positive for CD13 and/or CD33. The ages at diagnoses ranged from 2 months to 12 years. Median age was 4 years. The incidence of myeloid antigen coexpression was 23 per cent. Univariate analyses showed that presenting features were similar between My+B and My-B with regard to age, sex, race, FAB morphology, white cell count, hemoglobin level, platelet count, liver/spleen size, central nervous system or mediastinal involvement, presence of lymphadenopathy, and proportion of blast cells detected in the marrow. Treatment outcome were not significant between the two groups. The 2-year event free survival was achieved in 44 per cent of My+B and 57 per cent of My-B (p = 0.11). The 2-year overall survival rates were 62 per cent for My+B vs. 77 per cent for My-B (p = 0.08). This study demonstrates that myeloid antigen coexpression is fairly common and constitutes 23 per cent of childhood ALL within the Malaysian population and that it is not an adverse risk factor in childhood ALL.
  10. Barrientosiimonas humi gen. nov., sp. nov., an actinobacterium of the family Dermacoccaceae
    Lee LH, Cheah YK, Sidik SM, Xie QY, Tang YL, Lin HP, et al.
    Int J Syst Evol Microbiol, 2013 Jan;63(Pt 1):241-248.
    PMID: 22389286 DOI: 10.1099/ijs.0.038232-0
    Three novel actinobacteria, strains 39(T), 40 and 41, were isolated from soil collected from Barrientos Island in the Antarctic. The taxonomic status of these strains was determined using a polyphasic approach. Comparison of 16S rRNA gene sequences revealed that strain 39(T) represented a novel lineage within the family Dermacoccaceae and was most closely related to members of the genera Demetria (96.9 % 16S rRNA gene sequence similarity), Branchiibius (95.7 %), Dermacoccus (94.4-95.3 %), Calidifontibacter (94.6 %), Luteipulveratus (94.3 %), Yimella (94.2 %) and Kytococcus (93.1 %). Cells were irregular cocci and short rods. The peptidoglycan type was A4α with an L-Lys-L-Ser-D-Asp interpeptide bridge. The cell-wall sugars were galactose and glucose. The major menaquinone was MK-8(H(4)). The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, phosphoglycolipid, two glycolipids and one unknown phospholipid. The acyl type of the cell-wall polysaccharide was N-acetyl. The major cellular fatty acids were anteiso-C(17 : 0) (41.97 %), anteiso-C(17 : 1)ω9c (32.16 %) and iso-C(16 : 0) (7.68 %). The DNA G+C content of strain 39(T) was 68.4 mol%. On the basis of phylogenetic and phenotypic differences from other genera of the family Dermacoccaceae, a novel genus and species, Barrientosiimonas humi gen. nov., sp. nov., is proposed; the type strain of the type species is 39(T) (=CGMCC 4.6864(T) = DSM 24617(T)).
  11. Molecular characterization of Antarctic actinobacteria and screening for antimicrobial metabolite production
    Lee LH, Cheah YK, Mohd Sidik S, Ab Mutalib NS, Tang YL, Lin HP, et al.
    World J Microbiol Biotechnol, 2012 May;28(5):2125-37.
    PMID: 22806035 DOI: 10.1007/s11274-012-1018-1
    The present study aimed to isolate actinobacteria from soil samples and characterized them using molecular tools and screened their secondary metabolites for antimicrobial activities. Thirty-nine strains from four different location of Barrientos Island, Antarctica using 12 types of isolation media was isolated. The isolates were preceded to screening of secondary metabolites for antimicrobial and antifungal activities. Using high-throughput screening methods, 38% (15/39) of isolates produced bioactive metabolites. Approximately 18% (7/39), 18% (7/39), 10% (4/39) and 2.5% (1/39) of isolates inhibited growth of Candida albicans ATCC 10231(T), Staphylococcus aurues ATCC 51650(T), methicillin-resistant Staphylococcus aurues (MRSA) ATCC BAA-44(T) and Pseudomonas aeruginosa ATCC 10145(T), respectively. Molecular characterization techniques like 16S rRNA analysis, Enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR), Random amplified polymorphic DNA (RAPD) and composite analyses were used to characterize the actinobacteria strains. Analysis of 16S rRNA sequences is still one of the most powerful methods to determine higher taxonomic relationships of Actinobacteria. Both RAPD and ERIC-PCR fingerprinting have shown good discriminatory capability but RAPD proved to be better in discriminatory power than ERIC-PCR. Our results demonstrated that composite analysis of both fingerprinting generally increased the discrimination ability and generated best clustering for actinobacteria strains in this study.
  12. Fulltext Analysis of Antarctic proteobacteria by PCR fingerprinting and screening for antimicrobial secondary metabolites
    Lee LH, Cheah YK, Nurul Syakima AM, Shiran MS, Tang YL, Lin HP, et al.
    Genet. Mol. Res., 2012;11(2):1627-41.
    PMID: 22782582 DOI: 10.4238/2012.June.15.12
    Fifty-seven proteobacterium species were successfully isolated from soils of Barrientos Island of the Antarctic using 11 different isolation media. Analysis of 16S rDNA sequencing of these isolates showed that they belonged to eight different genera, namely Bradyrhizobium, Sphingomonas, Methylobacterium, Caulobacter, Paracoccus, Ralstonia, Rhizobium, and Staphylococcus. All isolates were studied for capability of producing antimicrobial and antifungal secondary metabolites using high-throughput screening models. Approximately 23 (13/57) and 2% (1/57) of isolates inhibited growth of Candida albicans ATCC 10231(T) and Staphylococcus aureus ATCC 51650(T), respectively. These results indicated that proteobacterium species isolates from Antarctic could serve as potential source of useful bioactive metabolites. Enterobacterial repetitive intergenic consensus (ERIC)-PCR fingerprinting produced nine clusters and 13 single isolates, with a high D value of 0.9248. RAPD fingerprinting produced six clusters and 13 single isolates, with a relatively low D value of 0.7776. ERIC-PCR analysis proved to have better discrimination capability than RAPD analysis and generated better clustering for all proteobacterium species isolates. We conclude that ERIC-PCR is a robust, reliable and rapid molecular typing method for discriminating different genera of proteobacteria.
  13. Fulltext Abnormalities of chromosome 11Q in three cases of acute myeloid leukemia
    Ten SK, Khor MK, Khalid H, Lin HP, Ng SC, Cheong SK, et al.
    Singapore Med J, 1992 Apr;33(2):164-6.
    PMID: 1621121
    The haematological findings and case history of 3 patients with the association of acute myeloid leukemia and translocation involving the long arm of chromosome no. 11 are presented. The recipient chromosome for the translocated material from chromosome 11 differs in all the three cases being namely chromosomes 1, 10 and 17.
  14. Testicular relapse in childhood acute lymphoblastic leukaemia in Malaysia, 1967-82
    Lin HP, Taib NM, Singh P, Sinniah D, Lam KL
    Aust Paediatr J, 1984 Mar;20(1):53-6.
    PMID: 6590027
    From 1967-82, 9 children with testicular relapse (TR) of acute lymphoblastic leukaemia (ALL) were diagnosed out of 99 boys treated, an incidence of 9.1%. The median time from the onset of ALL until diagnosis was 28 months (range 3-41 months). All were asymptomatic; six were detected on routine examination while three were diagnosed only on biopsy. Routine biopsy prior to stopping chemotherapy is useful in detecting occult TR. Biopsies should be done on both the testes regardless of the clinical findings. The age, leucocyte count and hepatosplenomegaly at diagnosis of ALL were not found to be significant factors in influencing relapse. Eight children were in bone marrow remission at the time of TR, but three had preceding or concurrent meningeal leukaemia while in the other five the testis was the first and only site of relapse. Radiotherapy was effective in local disease control but failed to prevent bone marrow relapse in all except two patients despite continuation of chemotherapy. The median time from onset of TR until bone marrow relapse was 7 months (range 3-13 months) and the median time until death, was 11 months (range 6-18 months). The frequency of testicular relapse may be related to the intensity of either the initial induction therapy or the consolidation chemotherapy. Further studies are required to determine whether the incidence of testicular relapse will decline with more intensive early treatment.
  15. Bone marrow transplantation in Malaysia
    Lin HP, Chan LL, Tan A, Ariffin WA, Lam SK
    Bone Marrow Transplant, 1994 Jun;13(6):725-9.
    PMID: 7920303
    The sole BMT centre in Malaysia caters only for children. Since 1987, 89 transplants have been performed using reverse barrier nursing techniques. The overall survival rate is 73% with the majority of survivors leading normal lives. The early and late infection rates of 46% and 13%, respectively, are comparable to those of other centres. Although the early septicaemia rate is 36% the immediate mortality rate is < 10%. GVHD is less frequent and severe and the interstitial pneumonitis rate lower than that in the West. The average cost of US $8000 per transplant is much lower than the cost of a transplant performed overseas. Thus we believe that our paediatric BMT programme is simple and cost-effective.
  16. Haemophagocytic lymphohistiocytosis in Malaysian children
    Ariffin H, Lum SH, Cheok SA, Shekhar K, Ariffin WA, Chan LL, et al.
    J Paediatr Child Health, 2005 Mar;41(3):136-9.
    PMID: 15790325
    To study the clinical presentation, therapy and outcome of children diagnosed with both primary and secondary haemophagocytic lymphohistiocytosis (HLH) at the University of Malaya Medical Centre.
  17. Pediatric Vaginal Yolk Sac Tumor: Reappraisal of Treatment Strategy in a Rare Tumor at a Unique Location
    Rajagopal R, Ariffin H, Krishnan S, Abdullah WA, Lin HP
    J Pediatr Hematol Oncol, 2015 Jul;37(5):391-5.
    PMID: 25929614 DOI: 10.1097/MPH.0000000000000344
    Review of the management of 6 young girls with vaginal yolk sac tumor over 25 years showed that the α-fetoprotein levels normalized in 5/6 within 4 cycles of primary cisplatin, bleomycin, etoposide (PEB)/carboplatin, etoposide, bleomycin (JEB)/cisplatin, vinblastine, bleomycin (PVB) chemotherapy. Radioimaging revealed residual tissue but viable tumor was found in only 1 of 2 biopsied. Resection/biopsy is necessary to avoid giving additional primary chemotherapy or to identify patients who need different treatment. If markers do not decay appropriately, PEB/JEB/PVB chemotherapy should not be continued. Taxol-containing salvage chemotherapy regimens, adjuvant modern radiotherapeutic treatment, and fertility-saving curative surgery should then be considered. Despite having mostly advanced disease, 5/6 patients were cured, 2 with chemotherapy alone.
  18. Prenatal exclusion of severe factor VII deficiency
    Ariffin H, Millar DS, Cooper DN, Chow T, Lin HP
    J Pediatr Hematol Oncol, 2003 May;25(5):418-20.
    PMID: 12759632
    A nonconsanguineous asymptomatic couple, were identified as carriers of factor VII (FVII) deficiency when two of their newborn children died of massive intracranial hemorrhage secondary to severe congenital FVII deficiency. Complete sequence analysis of the factor VII (F7) gene in this couple indicated that the mother was heterozygous for an A to G transition at position -2 of the exon 5 acceptor splice site, and the father was heterozygous for a G to T transversion at position +1 of the exon 6 donor splice site. This information allowed us to exclude a compound heterozygous deficiency state in a subsequent pregnancy using PCR/direct sequencing of the F7 gene using DNA obtained from chorionic villi at 10 weeks' gestation. Our experience with the family reported here further supports the conclusion that mutation-specific detection is reliable in the prenatal exclusion of severe bleeding disorders.
  19. Cure of beta-thalassaemia major by umbilical cord blood transplantation--a case report of Malaysia's first cord blood transplantation
    Chan LL, Lin HP
    J Trop Pediatr, 1999 Aug;45(4):243-5.
    PMID: 10467839
    A 25-month-old boy with beta-thalassaemia major was presented with an opportunity for umbilical cord blood transplantation when his unborn sibling was diagnosed in utero to be a beta-thalassaemia carrier and also human leucocyte antigen compatible. A barely adequate amount of cord blood was collected at the birth of his sibling and infused into the patient after appropriate chemo-conditioning. Engraftment occurred without major complications. The subject is now alive and well 9 months post-transplant, thus marking our first success in umbilical cord blood transplantation.
  20. Single-daily ceftriaxone plus amikacin versus thrice-daily ceftazidime plus amikacin as empirical treatment of febrile neutropenia in children with cancer
    Ariffin H, Arasu A, Mahfuzah M, Ariffin WA, Chan LL, Lin HP
    J Paediatr Child Health, 2001 Feb;37(1):38-43.
    PMID: 11168867
    OBJECTIVE: Empirical antibiotic treatment for febrile neutropenic patients has been the mainstay of treatment for many years. Beta-lactam antibiotics and aminoglycosides have been the most frequently used drug combination. The purpose of this study was to evaluate the efficacy, safety, tolerance and costs of single-daily ceftriaxone plus amikacin versus thrice-daily dose of ceftazidime plus amikacin.

    METHODOLOGY: One hundred and ninety-one episodes of fever and neutropenia in 128 patients from October 1997 to December 1998 were included in a prospective, open-label, single-centre study. Patients were randomly assigned to either treatment group and evaluated as successes or failures according to defined criteria. Daily assessments were made on all patients and all adverse events recorded. Univariate and multivariate analysis of outcomes and a cost analysis were carried out.

    RESULTS: There were 176 evaluable patient-episodes with 51.1% in the single-daily ceftriaxone-amikacin group and 48.9% in the ceftazidime-amikacin group. There were 50 positive blood cultures: 12 Gram-positive bacteria, 33 Gram-negative bacteria and five fungi. Pseudomonas aeruginosa (P. aeruginosa) accounted for 14% of total isolates. The overall success rate was 55.5% in the ceftriaxone group compared to 51.2% in the ceftazidime group (P = 0.56). Mean time to defervescence was 4.2 days in the single-daily group and 4.3 days in the thrice-daily group. There were nine infection-related deaths; five in the single-daily ceftriaxone group. The daily cost of the once-daily regime was 42 Malaysian Ringgit less than the thrice-daily regime. There was a low incidence of adverse effects in both groups, although ototoxicity was not evaluable.

    CONCLUSIONS: The once-daily regime of ceftriaxone plus amikacin was as effective as the 'standard' combination of thrice-daily ceftazidime and amikacin with no significant adverse effects in either group. The convenience and substantial cost benefit of the once-daily regime will be particularly useful in developing countries with limited health resources and in centres with a low prevalence of P. aeruginosa.

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