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Outcome of treatment in adult acute lymphoblastic leukaemia in an Asian population: comparison with previous multicentre German study

Bosco I, Teh A

Leukemia, 1995 Jun;9(6):951-4.
PMID: 7596183

Reports on the outcome of treatment in ALL in Asian (non-Caucasian) adults have been few, and published results compare very unfavourably with results of treatment from 'Western' centres. Seventy-four newly diagnosed Malaysian patients with ALL between the ages of 15 and 69 were treated from 1986 to 1990. The clinical features and prognostic factors were similar to those reported in 'Western' series. The chemotherapy protocol utilized was adapted from the one used by Hoelzer et al in the multicentre German study. The complete remission rate was 73%. The probability of continuous complete remission at 5 years was 29% with a median duration of remission of 15 months. This compares with Hoelzer's initial results of 77% CR rate and 35% CCR at 5 years. Patients with an initial white cell count of less than 30 x 10(9)/l at presentation were found to have a significantly better disease-free survival than those with a count of more than 30 x 10(9)/l (35 vs 22%, P = 0.026, univariate analysis). There was no difference in leukaemia-free survival according to age, sex, ethnic group, or immunophenotype. These results show that the use of moderately intensive chemotherapy protocols in Asian (non-Caucasian) patients achieves similar results to those used in Caucasians. We also showed that the difficulties in 'curing' approximately 70% of adult patient with ALL are universal.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality
Biphenotypic hybrid acute leukaemia detected by two colour flow cytometry

Gudum HR, Chin YM, Menaka N, Jeyaranee S, Lin HP, Tay A

Malays J Pathol, 1992 Jun;14(1):25-8.
PMID: 1469914

Immunophenotypic studies using immunofluorescent flow cytometry were performed on the blast cells of 36 patients with acute leukaemia using a panel of eight monoclonal antibodies. Six patients had blasts which co-expressed markers for lymphoid and myeloid differentiation, and which were therefore defined as biphenotypic hybrid acute leukaemia. Of the six, three patients were in the paediatric age group (below 12 years old) while the other three were more than 12 years old. Peripheral blood counts were variable; however, bone marrow infiltration was extensive (blasts > or = 75% in all). At the time of study, remission was achieved in only two patients. The authors' data show that biphenotypic hybrid acute leukaemia is not rare in Malaysia. This represents a subgroup of acute leukaemia identifiable by immunophenotyping but not by the French-American-British classification based on morphological and basic cytochemical studies alone. The recognition of this subgroup is important for both practical and theoretical reasons. There are implications for treatment of the individual patient because treatment directed at a single lineage may not be effective. The two colour flow cytometry proved to be a useful tool for diagnosis and classification of acute leukaemia.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/classification; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology*
Causative Pathogens of Febrile Neutropaenia in Children Treated for Acute Lymphoblastic Leukaemia

Lam JC, Chai JY, Wong YL, Tan NW, Ha CT, Chan MY, et al.

Ann Acad Med Singap, 2015 Nov;44(11):530-4.
PMID: 27089960

INTRODUCTION: Treatment of acute lymphoblastic leukaemia (ALL) using intensive chemotherapy has resulted in high cure rates but also substantial morbidity. Infective complications represent a significant proportion of treatment-related toxicity. The objective of this study was to describe the microbiological aetiology and clinical outcome of episodes of chemotherapy-induced febrile neutropaenia in a cohort of children treated for ALL at our institution.
MATERIALS AND METHODS: Patients with ALL were treated with either the HKSGALL93 or the Malaysia-Singapore (Ma-Spore) 2003 chemotherapy protocols. The records of 197 patients who completed the intensive phase of treatment, defined as the period of treatment from induction, central nervous system (CNS)-directed therapy to reinduction from June 2000 to January 2010 were retrospectively reviewed.
RESULTS: There were a total of 587 episodes of febrile neutropaenia in 197 patients, translating to an overall rate of 2.98 episodes per patient. A causative pathogen was isolated in 22.7% of episodes. An equal proportion of Gram-positive bacteria (36.4%) and Gram-negative bacteria (36.4%) were most frequently isolated followed by viral pathogens (17.4%), fungal pathogens (8.4%) and other bacteria (1.2%). Fungal organisms accounted for a higher proportion of clinically severe episodes of febrile neutropaenia requiring admission to the high-dependency or intensive care unit (23.1%). The overall mortality rate from all episodes was 1.5%.
CONCLUSION: Febrile neutropaenia continues to be of concern in ALL patients undergoing intensive chemotherapy. The majority of episodes will not have an identifiable causative organism. Gram-positive bacteria and Gram-negative bacteria were the most common causative pathogens identified. With appropriate antimicrobial therapy and supportive management, the overall risk of mortality from febrile neutropaenia is extremely low.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*
Fulltext Invasive aspergillosis in paediatric oncology patients

Muda Z, Ibrahim H, Abdulrahman EJ, Menon BS, Zahari Z, Zaleha AM, et al.

Med J Malaysia, 2008 Dec;63(5):415-6.
PMID: 19803305 MyJurnal

Invasive aspergillosis predominantly occurs in immunocompromised patients and is often resistant to different therapeutically strategies. However, mortality significantly increases if the central nervous system is affected. In this report we describe two cases of invasive aspergilosis, one with kidney involvement with a successful treatment while the other with pulmonary and cerebral involvement with a grave outcome.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/microbiology*
Hereditary elliptocytosis with acute lymphoblastic leukaemia

TI TS

Med J Malaya, 1962 Mar;16:214-8.
PMID: 13921142
Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma*
Fulltext Genetic aberrations in childhood acute lymphoblastic leukaemia: application of high-density single nucleotide polymorphism array

Sulong S

Malays J Med Sci, 2010 Jul;17(3):5-12.
PMID: 22135543

Screening of the entire human genome using high-density single nucleotide polymorphism array (SNPA) has become a powerful technique used in cancer genetics and population genetics studies. The GeneChip® Mapping Array, introduced by Affymetrix, is one SNPA platform utilised for genotyping studies. This GeneChip system allows researchers to gain a comprehensive view of cancer biology on a single platform for the quantification of chromosomal amplifications, deletions, and loss of heterozygosity or for allelic imbalance studies. Importantly, this array analysis has the potential to reveal novel genetic findings involved in the multistep development of cancer. Given the importance of genetic factors in leukaemogenesis and the usefulness of screening the whole genome, SNPA analysis has been utilised in many studies to characterise genetic aberrations in childhood acute lymphoblastic leukaemia.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma
Fulltext Cytotoxicity of leukemic cells by nypa fruticans through regulation of adiponectin expression

Mohammad Fauzan Zainudin, Ummu Afifah Fadzir, Athirah Rosdi, Muhammad Farid Johan, Ridzwan Hashim, Ridhwan Abdul Wahab, et al.

International Journal of Allied Health Sciences, 2017;1(2):28-43.
MyJurnal

Acute lymphoblastic leukemia (ALL) is the most common leukemia subtypes among paediatrics in Malaysia. Although treatment options are available but some patients remain incurable, some undergo relapse and many experiences adverse effects by the conventional therapies. Thus, we aim to investigate possible treatment alternative by studying the antileukemogenesis properties of concentrated Nypa fruticans sap called nisaan by focusing on adiponectin expression.
Our study model was CCRF-CEM, an acute lymphoblastic leukemia cell lines. The cells were treated with nisaan at a range of concentration and treated for 24, 48 and 72 hours followed by determination of the leukemic cells viability using tryphan blue method. Effective nisaan concentrations that significantly reduced the cells viability were again treated to the cells followed by determination of the cell proliferation using BrdU colorimetric kit and adiponectin level using adiponectin ELISA kit.
The results showed that, increase concentration of nisaan treatment reduced the cells viability and cells proliferation and enhance the adiponectin level in the leukemic cells.
This preliminary data suggest that Nypa fruticans might has the antileukemogenesis effect on acute lymphoblastic cells by regulating the adiponectin expression.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma
Fulltext Optic nerve involvement as a first manifestation of acute lymphoblastic leukaemia after remission

Peyman M, Hieng TL, Subrayan V

BMJ Case Rep, 2011;2011.
PMID: 22698906 DOI: 10.1136/bcr.11.2010.3517
Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology
Comparison of myeloperoxidase detection by flow cytometry using two different clones of monoclonal antibodies

Leong CF, Kalaichelvi AV, Cheong SK, Hamidah NH, Rahman J, Sivagengei K

Malays J Pathol, 2004 Dec;26(2):111-6.
PMID: 16329563

Myeloperoxidase (MPO) is present in azurophilic granules which appear in the promyelocyte stage of differentiation and is expressed in granulomonocytic cells. MPO is usually detected by cytochemistry. The demonstration of peroxidase in at least 3% of bone marrow blasts defines an acute leukaemia as acute myeloblastic leukaemia (AML). MPO is important in distinguishing acute myeloblastic leukaemia (AML) from acute lymphoblastic leukaemia (ALL). It is difficult to diagnose AML with minimal evidence of myeloid differentiation (AML- M0) by conventional light microscopy. However, these AML-M0 blasts can be detected by monoclonal antibodies. Anti-MPO recognizes the enzymatically inactive precursor forms of MPO. There are a few commercially available monoclonal antibodies against MPO. In this study, we evaluated two monoclonal antibodies against MPO from different commercial sources.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/enzymology
Fulltext Combination of Pyridoxine and Thiamine Treatment in Bilateral Induced Ptosis in a Child: Case Report and Review of Literature

Chai KS, Norsarwany M, Shatriah I

Cureus, 2017 Aug 16;9(8):e1573.
PMID: 29057185 DOI: 10.7759/cureus.1573

Ptosis is a rare side effect of vincristine chemotherapy in patients treated for cancer. We report a case of a child with common B-cell acute lymphoblastic leukemia who developed bilateral moderate ptosis following the chemotherapy protocol of the United Kingdom Acute Lymphoblastic Leukemia (ALL) regimen A. The patient showed dramatic clinical improvement after a combination of oral pyridoxine and thiamine treatment. We provide a literature review of this uncommon presentation.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma
Relationship between oral health status and hematological values in pediatric leukemic patients: an evaluative survey

Venkataraghavan K, Majithia U, Choudhary P, Trivedi K, Shah S

J Contemp Dent Pract, 2016 Jan-Feb;15(5):614-7.
PMID: 25707835

INTRODUCTION: Leukemia is a malignancy of the bone marrow and constitutes 30% of all childhood cancers. The leukemic condition itself and its therapy cause oral signs and symptoms with significant morbidity.
AIMS AND OBJECTIVES: The aim of this study was to review the oral health status in children with leukemia and relate the gingival and periodontal findings to the changes in their hematological values.
MATERIALS AND METHOD: The oral health status in 47 pediatric leukemic patients in the age group of 6 to 14 years was assessed using the dmft/DMFT index, OHI(S) index and modified gingival index (MGI). Their hematological reports on the day of examination were obtained. The patients were divided into three groups based on the status of treatment. The relation between the platelet count and the WBC count with the MGI score was checked.
RESULTS: The highest dmf and DMF scores were seen in patients who were currently under treatment. Though an inverse relation was seen between the platelet count and the MGI score, a statistically significant value was not obtained.
CONCLUSION: A longitudinal follow-up of patients should be carried out in order to establish a relation between the hematological parameters and the gingival inflammation score

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma/radiotherapy
Fulltext S-phase fraction and pro-inflammatory cytokine expressions in acute lymphoblastic leukaemia

Maha A, Cheong SK, Leong CF, Seow HF

Malaysian Journal of Medicine and Health Sciences, 2005;1(1):41-51.

Objective: Despite much progress in treatment strategies, long term survival of adult ALL is still inferior to that in children. The underlying mechanisms for these differences are largely unknown. Intensification of contemporary therapy has also resulted in many children being over-treated. The action of chemotherapeutic drugs used in the treatment of ALL includes cell cycle dependent agents which are effective on cells that are proliferating. Cell proliferation in haemopoietic cells is controlled by cytokines. Thus, we proposed to study the cell cycle profile of ALL cases and also expression of cytokines to determine their role in affecting treatment outcome in the different age groups.
Methods: We determined the S-phase fraction from the cell cycle profile by flowcytometry and tested the expressions of cytokine IL-1beta, IL-6, IL-18, IFN-gamma, TNF-alpha and GM-CSF using RT-PCR in de novo ALL cases.
Results: We found a significantly higher S-phase fraction in samples from children 2-10 years old compared to the older age group (>10 years old) (p=0.001). GM-CSF was found to be expressed in a significantly lower percentage of children compared to adults (p=0.008).
Conclusion: Our results implied that GM-CSF may have induced cell cycle arrests in adult ALL resulting in a lower percentage of S-phase fraction. This may contribute to the poorer prognosis in adult ALL because non-cycling blasts are less sensitive to some chemotherapeutic drugs.
Keywords: ALL, S-phase fraction, GM-CSF, age

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma
Polymorphism of ITPA 94C>A and risk of adverse effects among patients with acute lymphoblastic leukaemia treated with 6-mercaptopurine

Wan Rosalina WR, Teh LK, Mohamad N, Nasir A, Yusoff R, Baba AA, et al.

J Clin Pharm Ther, 2012 Apr;37(2):237-41.
PMID: 21545474 DOI: 10.1111/j.1365-2710.2011.01272.x

Genetic polymorphisms of thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphohydrolase (ITPA 94C>A) contribute to variable responses, including fatal adverse effects, among subjects treated with 6-mercaptopurine (6-MP). Our objectives were to investigate the distribution of specific TPMT and ITPA genotypes in healthy subjects and patients with acute lymphoblastic leukaemia (ALL) from the three main ethnic groups (Malays, Chinese and Indians) in Malaysia and the association of the polymorphisms with adverse effects of 6-MP.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
The differential metabolite profiles of acute lymphoblastic leukaemic patients treated with 6-mercaptopurine using untargeted metabolomics approach

Bannur Z, Teh LK, Hennesy T, Rosli WR, Mohamad N, Nasir A, et al.

Clin Biochem, 2014 Apr;47(6):427-31.
PMID: 24582698 DOI: 10.1016/j.clinbiochem.2014.02.013

Acute lymphoblastic leukaemia (ALL) has posed challenges to the clinician due to variable patients' responses and late diagnosis. With the advance in metabolomics, early detection and personalised treatment are possible.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism*
Fulltext Ocular involvement in acute lymphoblastic leukaemia

Tan AK, Azman A, Hoe TS, Rohana T

Med J Malaysia, 1994 Dec;49(4):409-11.
PMID: 7674978

A six-year-old boy, a known case of acute lymphoblastic leukaemia (ALL) on remission since 1991 presented with leukocoria and poor vision of the left eye for two days' duration. Examination revealed endophthalmitis in the left eye with raised intraocular pressure. Anterior chamber paracentesis with vitreous biopsy confirmed a diagnosis of ocular involvement. Further investigation revealed that he also had bone marrow and central nervous system relapse. Clinical manifestation and treatment modalities of ocular involvement in leukaemia are discussed.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology*
Fulltext Parental reports of behavioural outcome among paediatric leukaemia survivors in Malaysia: a single institution experience

Hamidah A, Sham Marina M, Tamil AM, Loh CK, Zarina LA, Jamal R, et al.

Trop Med Int Health, 2014 Oct;19(10):1177-84.
PMID: 25047756 DOI: 10.1111/tmi.12358

To determine the behavioural impact of chemotherapy in survivors of acute lymphoblastic leukaemia (ALL) treated with chemotherapy only and to identify treatment-related or sociodemography-related factors that might be associated with behavioural outcome.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*
Fulltext Disseminated fusariosis and endogenous fungal endophthalmitis in acute lymphoblastic leukemia following platelet transfusion possibly due to transfusion-related immunomodulation

Kah TA, Yong KC, Rahman RA

BMC Ophthalmol, 2011;11:30.
PMID: 22044440 DOI: 10.1186/1471-2415-11-30

To report a case of disseminated fusariosis with endogenous endophthalmitis in a patient with acute lymphoblastic leukemia. Transfusion-associated immune modulation secondary to platelet transfusion could play an important role in the pathophysiology of this case.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy*
Fulltext Bone marrow necrosis preceding infantile acute lymphoblastic leukaemia

Eusni RM, Hamidah Hussin N, Zarina AL, Rahman J

Malays J Pathol, 2007 Dec;29(2):113-7.
PMID: 19108404 MyJurnal

We report a case of bone marrow necrosis preceding infantile acute lymphoblastic leukaemia (ALL). Bone marrow necrosis is a rare antemortem event and has been known to be present in many conditions, notably in haematological malignancies like acute lymphoblastic leukaemia. This case was a 6-month-old Chinese boy who was referred to Hospital Universiti Kebangsaan Malaysia for further investigation of pancytopaenia, high-grade fever, bloody diarrhoea and petechial rashes for one week. His first bone marrow aspirate revealed bone marrow necrosis. His clinical condition improved after ten days. However, his full blood picture then revealed the presence of 5% blast cells. His subsequent marrow 2 weeks later revealed acute lymphoblastic leukaemia (FAB-L1) and immunophenotyping showed precursor B acute lymphoblastic leukaemia-null type. He was started on United Kingdom Acute Lymphoblastic leukaemia (UK ALL) Infantile Leukaemia protocol, however, he defaulted treatment after 3 days. Mode of presentation, mechanism of disease and laboratory investigations and outline of treatment will be discussed.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/physiopathology
Fulltext Induction of selective cytotoxicity and apoptosis in human T4-lymphoblastoid cell line (CEMss) by boesenbergin a isolated from boesenbergia rotunda rhizomes involves mitochondrial pathway, activation of caspase 3 and G2/M phase cell cycle arrest

Ng KB, Bustamam A, Sukari MA, Abdelwahab SI, Mohan S, Buckle MJ, et al.

BMC Complement Altern Med, 2013;13:41.
PMID: 23432947 DOI: 10.1186/1472-6882-13-41

Boesenbergia rotunda (Roxb.) Schlecht (family zingiberaceae) is a rhizomatous herb that is distributed from north-eastern India to south-east Asia, especially in Indonesia, Thailand and Malaysia. Previous research has shown that the crude extract of this plant has cytotoxic properties. The current study examines the cytotoxic properties of boesenbergin A isolated from Boesenbergia rotunda.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism; Precursor Cell Lymphoblastic Leukemia-Lymphoma/physiopathology
Heterogeneous t(4;11) fusion transcripts in two infants with acute lymphoblastic leukemia

Gill HK, Ten SK, Dhaliwal JS, Moore S, Hassan R, Karim FA, et al.

Malays J Pathol, 2004 Dec;26(2):105-10.
PMID: 16329562

An RT-PCR assay detected the t(4;11) translocation in two infants with acute lymphoblastic leukemia (ALL). Case P76 was a 10-month-old, female infant, who presented with a WBC of 137.4 x 10(9)/l and a pre-pre-B ALL immunophenotype. Case P120 was a 6-month-old female infant, with a WBC > 615 x 10(9)/l and a pre-pre-B ALL immunophenotype. RT-PCR of cDNA from both these cases generated a 656 bp and a 542 bp respectively, which sequencing confirmed as t(4;11) fusion transcripts. The primers and conditions selected for this assay are compatible with a one-step multiplex PCR for the main translocations in childhood ALL.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology

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