Displaying publications 1 - 20 of 115 in total

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  1. Reddy SC, Menon BS
    Acta Ophthalmol Scand, 1998 Dec;76(6):700-3.
    PMID: 9881556
    PURPOSE: To determine the prevalence of ocular manifestations in childhood acute leukaemia at the time of presentation.

    METHODS: Eighty-two children with acute leukaemia were examined for ocular lesions within two days of diagnosis before starting chemotherapy. The detailed ocular examination of both eyes was carried out by the ophthalmologist irrespective of the presence or absence of eye symptoms in all cases.

    RESULTS: Only 3 out of 82 children presented with eye symptoms (3.6%). However, ocular changes were found in 14 children (17%); ten with lymphoblastic and four with myeloid leukaemia. The ocular lesions observed were proptosis, intraretinal haemorrhages, white centered haemorrhages, cotton wool spots, macular haemorrhage, subhyaloid haemorrhage, vitreous haemorrhage, papilloedema, cortical blindness, sixth nerve palsy, and exudative retinal detachment with choroidal infiltration.

    CONCLUSION: In view of the high prevalence of asymptomatic ocular lesions in childhood acute leukaemia, routine ophthalmic examination should be included as a part of evaluation at the time of diagnosis.

    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis
  2. Reddy SC, Jackson N
    Acta Ophthalmol Scand, 2004 Feb;82(1):81-5.
    PMID: 14738490
    PURPOSE: To determine the prevalence of retinal changes in newly diagnosed acute leukaemia patients, and to establish the relationship between retinal lesions and haematological parameters in these patients.

    METHODS: A total of 127 patients with acute leukaemia (myeloid and lymphoid), of both genders, aged between 13 and 77 years, were examined by an ophthalmologist for retinal changes using direct/indirect ophthalmoscopy within 2 days of diagnosis before starting chemotherapy.

    RESULTS: Retinal lesions were seen in 62 cases (49%), with intraretinal haemorrhages being the most common lesion (42%). A high white blood cell count was significantly associated with intraretinal haemorrhages (p = 0.04) and white-centred haemorrhages (p = 0.001), while a low platelet count was significantly associated with intraretinal haemorrhages (p = 0.03) in acute myeloid leukaemia patients.

    CONCLUSIONS: A high white blood cell count may be considered as important as a low platelet count in the pathogenesis of leukaemic retinopathy.

    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
  3. Ibrahim K, Daud SS, Seah YL, Yeoh AE, Ariffin H, Malaysia-Singapore Leukemia Study Group
    Ann Clin Lab Sci, 2008;38(4):338-43.
    PMID: 18988926
    Childhood acute lymphoblastic leukaemia (ALL) is a heterogenous disease in which oncogene fusion transcripts are known to influence the biological behaviour of the different ALL subtypes. Screening for prognostically important transcripts is an important diagnostic step in treatment stratification and prognostication of affected patients. We describe a SYBR-Green real-time multiplex PCR assay to screen for transcripts TEL-AML1, E2A-PBX1, MLL-AF4, and the two breakpoints of BCR-ABL (p190 and p210). Validation of the assay was based on conventional karyotyping results. This new assay provides a rapid, sensitive, and accurate detection method for prognostically important transcripts in childhood ALL.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics*
  4. 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*
  5. Ng SC, Wong TK, Lin HP
    Ann Acad Med Singap, 1989 Nov;18(6):721-3.
    PMID: 2624424
    The simultaneous expression of both lymphoid and myeloid phenotypic features in acute leukaemia is rare. We report 3 cases of biphenotypic hybrid acute leukaemia seen in our institution. All 3 patients achieved remission with treatment for acute lymphoblastic leukaemia but two subsequently relapsed while on treatment. The hybrid acute leukaemias are important areas for further research both for delineation of basic biology and choice of optimal treatment.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology*
  6. Batool T, Makky EA, Jalal M, Yusoff MM
    Appl Biochem Biotechnol, 2016 Mar;178(5):900-23.
    PMID: 26547852 DOI: 10.1007/s12010-015-1917-3
    L-asparaginase (LA) catalyzes the degradation of asparagine, an essential amino acid for leukemic cells, into ammonia and aspartate. Owing to its ability to inhibit protein biosynthesis in lymphoblasts, LA is used to treat acute lymphoblastic leukemia (ALL). Different isozymes of this enzyme have been isolated from a wide range of organisms, including plants and terrestrial and marine microorganisms. Pieces of information about the three-dimensional structure of L-asparaginase from Escherichia coli and Erwinia sp. have identified residues that are essential for catalytic activity. This review catalogues the major sources of L-asparaginase, the methods of its production through the solid state (SSF) and submerged (SmF) fermentation, purification, and characterization as well as its biological roles. In the same breath, this article explores both the past and present applications of this important enzyme and discusses its future prospects.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma
  7. Mehde AA, Yusof F, Adel Mehdi W, Zainulabdeen JA
    Asian Pac J Cancer Prev, 2015;16(12):5059-62.
    PMID: 26163641
    BACKGROUND: ALL is an irredeemable disease due to the resistance to treatment. There are several influences which are involved in such resistance to chemotherapy, including oxidative stress as a result of the generation of reactive oxygen species (ROS) and presence of hypodiploid cells. Cluster of differentiation 26 (CD26), also known as dipeptidyl peptidase-4, is a 110 kDa, multifunctional, membrane-bound glycoprotein.

    AIM AND OBJECTIVES: The aim of this study was to evaluate the clinical significance of serum CD26 in patients with acute lymphoblastic leukaemia patients in the post remission induction phase, as well as the relationship between CD26 activity and the oxidative stress status.

    MATERIALS AND METHODS: CD26, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI), in addition to activity of related enzymes myeloperoxidase, glutathione- s-transferase and xanthine oxidase, were analysed in sixty children with acute lymphoblastic leukaemia in the post remission induction phase.

    RESULTS: The study showed significant elevation in CD26, TOS and OSI levels in patients with acute lymphoblastic leukaemia in the post remission induction phase in comparison to healthy control samples. In contrast, myeloperoxidase, glutathione-s-transferase and xanthine oxidase activities were decreased significantly. A significant correlation between CD26 concentration and some oxidative stress parameters was evident in ALL patients.

    CONCLUSIONS: Serum levels of CD26 appear to be useful as a new biomarker of oxidative stress in children with acute lymphoblastic leukaemia in the post remission induction phase, and levels of antioxidants must be regularly estimated during the treatment of children with ALL.

    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy
  8. Omer ME, Abu Bakar M, Adam M, Mustafa M
    Asian Pac J Cancer Prev, 2021 Apr 01;22(4):1045-1053.
    PMID: 33906295 DOI: 10.31557/APJCP.2021.22.4.1045
    OBJECTIVE: Cure rate models are survival models, commonly applied to model survival data with a cured fraction. In the existence of a cure rate, if the distribution of survival times for susceptible patients is specified, researchers usually prefer cure models to parametric models. Different distributions can be assumed for the survival times, for instance, generalized modified Weibull (GMW), exponentiated Weibull (EW), and log-beta Weibull. The purpose of this study is to select the best distribution for uncured patients' survival times by comparing the mixture cure models based on the GMW distribution and its particular cases.

    MATERIALS AND METHODS: A data set of 91 patients with high-risk acute lymphoblastic leukemia (ALL) followed for five years from 1982 to 1987 was chosen for fitting the mixture cure model. We used the maximum likelihood estimation technique via R software 3.6.2 to obtain the estimates for parameters of the proposed model in the existence of cure rate, censored data, and covariates. For the best model choice, the Akaike information criterion (AIC) was implemented.

    RESULTS: After comparing different parametric models fitted to the data, including or excluding cure fraction, without covariates, the smallest AIC values were obtained by the EW and the GMW distributions, (953.31/969.35) and (955.84/975.99), respectively. Besides, assuming a mixture cure model based on GMW with covariates, an estimated ratio between cure fractions for allogeneic and autologous bone marrow transplant groups (and its 95% confidence intervals) were 1.42972 (95% CI: 1.18614 - 1.72955).

    CONCLUSION: The results of this study reveal that the EW and the GMW distributions are the best choices for the survival times of Leukemia patients.
    .

    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality*
  9. Binti Yusof NS, Ameli F, Sabrina Florence Ch, Mustangin M, Abd Rahman F, Masir N
    Asian Pac J Cancer Prev, 2017 04 01;18(4):1045-1050.
    PMID: 28547939
    Aim: Abnormal expression patterns of beta-tubulin isotypes may provide a molecular rationale for the behaviour
    of lymphoma subtypes. In the present study class II and III beta-tubulin expression was assessed in non-neoplastic and
    neoplastic lymphoid tissues with reference to potential utility as new tumour biomarkers. Methods and results: In this
    cross-sectional study class II and III beta-tubulin expression was assessed in 304 neoplastic and 20 normal lymphoid
    tissues using qualitative and semi-quantitative immunohistochemistry. Class II beta-tubulin was found to be positive in
    the germinal centres, mantle zone and interfollicular regions of normal lymphoid tissues. It was also expressed in 15/15
    (100%) lymphoblastic lymphomas, 229/231 (99%) mature B cell lymphomas, 22/22 (100%) T/NK-cell lymphomas and
    36/36(100%) classical Hodgkin lymphomas. Class III beta-tubulin in contrast was germinal centre restricted and more
    selective, being found mainly in classical Hodgkin lymphomas (34/36 (94%)). It was also expressed in 58/171(34%)
    DLBCL, 11/12 (92%) mantle cell lymphomas and 6/6 (100%) Burkitt lymphomas. Other mature B cell, T/NK cell
    lymphomas and precursor lymphoblastic lymphomas were usually negative. Conclusions: Class II beta-tubulin shows
    ubiquitous expression in neoplastic and non-neoplastic lymphoisd tissues. In contrast, Class III beta-tubulin is germinal
    centre-restricted. Its consistent expression in classical Hodgkin lymphomas may point to use in the identification of
    Reed-Sternberg and Hodgkin cells. Its expression in a proportion of DLBCL, Burkitt and mantle cell lymphomas is of
    interest as this may be related to their aggressiveness.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma
  10. Chong ASS, Ahmad M, Mohd Harizan NB, Alias H, Iqbal Hussain R, Lateh A, et al.
    Asian Pac J Cancer Prev, 2023 Jun 01;24(6):1923-1929.
    PMID: 37378920 DOI: 10.31557/APJCP.2023.24.6.1923
    OBJECTIVE: The caregivers of children diagnosed with acute lymphoblastic leukaemia (ALL) are believed to experience post-traumatic stress symptoms (PTSS), depression and anxiety. This present study endeavoured to explore the prevalence and predictors of PTSS, depression, and anxiety among the caregivers of children with ALL.

    METHODS: Purposive sampling was used to select the 73 caregivers of children with ALL who participated in this cross-sectional study. The Post-traumatic Stress Disorder Checklist for DSM-5 (PCL-5), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) were used to measure psychological distress.

    RESULT: There was a low prevalence (11%) of post-traumatic stress disorder (PTSD) among the participants. Although all the criteria for PTSD were not met, a few post-traumatic symptoms remained, suggesting that PTSS was likely present. Most of the participants reported minimal symptoms of depression (79.5%) and anxiety (65.8%). Anxiety, depression, and ethnicity predicted the PTSS scores (R2 = .77, p =.000). Subsequently, depression predicted the PTSS scores (R2 = 0.42, p =0.000). Participants of 'Other' or 'Indigenous' ethnicity had lower PTSS scores and higher anxiety scores (R2 = 0.75, p =0.000) than participants of Malay ethnicity.

    CONCLUSION: The caregivers of children with ALL experience post-traumatic stress symptoms (PTSS), depression, and anxiety. These variables co-exist and may have different trajectories in different ethnic groups. Therefore, healthcare providers should take ethnicity and psychological distress into consideration when providing paediatric oncology treatment and care.

    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma*
  11. Chua LL, Rajasuriar R, Lim YAL, Woo YL, Loke P, Ariffin H
    BMC Cancer, 2020 Feb 24;20(1):151.
    PMID: 32093640 DOI: 10.1186/s12885-020-6654-5
    BACKGROUND: Alteration in gut microbiota has been recently linked with childhood leukemia and the use of chemotherapy. Whether the perturbed microbiota community is restored after disease remission and cessation of cancer treatment has not been evaluated. This study examines the chronological changes of gut microbiota in children with acute lymphoblastic leukemia (ALL) prior to the start-, during-, and following cessation of chemotherapy.

    METHODOLOGY: We conducted a longitudinal observational study in gut microbiota profile in a group of paediatric patients diagnosed with ALL using 16 s ribosomal RNA sequencing and compared these patients' microbiota pattern with age and ethnicity-matched healthy children. Temporal changes of gut microbiota in these patients with ALL were also examined at different time-points in relation to chemotherapy.

    RESULTS: Prior to commencement of chemotherapy, gut microbiota in children with ALL had larger inter-individual variability compared to healthy controls and was enriched with bacteria belonging to Bacteroidetes phylum and Bacteroides genus. The relative abundance of Bacteroides decreased upon commencement of chemotherapy. Restitution of gut microbiota composition to resemble that of healthy controls occurred after cessation of chemotherapy. However, the microbiota composition (beta diversity) remained distinctive and a few bacteria were different in abundance among the patients with ALL compared to controls despite completion of chemotherapy and presumed restoration of normal health.

    CONCLUSION: Our findings in this pilot study is the first to suggest that gut microbiota profile in children with ALL remains marginally different from healthy controls even after cessation of chemotherapy. These persistent microbiota changes may have a role in the long-term wellbeing in childhood cancer survivors but the impact of these changes in subsequent health perturbations in these survivors remain unexplored.

    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma/microbiology*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology
  12. Ng KB, Bustamam A, Sukari MA, Abdelwahab SI, Mohan S, Buckle MJ, et al.
    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
  13. 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*
  14. 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
  15. Raffali MAA, Boon Cong B, Muhammad SF, Che Hassan HH
    BMJ Case Rep, 2023 Sep 25;16(9).
    PMID: 37748814 DOI: 10.1136/bcr-2023-255396
    A man in his 20s with underlying chemorefractory primary T-lymphoblastic lymphoma and hypereosinophilia developed acute chest pain in the ward after readmission for disease progression. ECG showed widespread ST depression and serum troponin was markedly elevated. Transthoracic echocardiography showed diffused thrombus deposition with preserved ejection fraction consistent with eosinophilic myocarditis. The patient ultimately succumbed to the disease, after complications with severe hospital-acquired pneumonia.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma*
  16. Moriyama T, Yang YL, Nishii R, Ariffin H, Liu C, Lin TN, et al.
    Blood, 2017 Sep 07;130(10):1209-1212.
    PMID: 28659275 DOI: 10.1182/blood-2017-05-782383
    Prolonged exposure to thiopurines (eg, mercaptopurine [MP]) is essential for curative therapy in acute lymphoblastic leukemia (ALL), but is also associated with frequent dose-limiting hematopoietic toxicities, which is partly explained by inherited genetic polymorphisms in drug metabolizing enzymes (eg, TPMT). Recently, our group and others identified germ line genetic variants in NUDT15 as another major cause of thiopurine-related myelosuppression, particularly in Asian and Hispanic people. In this article, we describe 3 novel NUDT15 coding variants (p.R34T, p.K35E, and p.G17_V18del) in 5 children with ALL enrolled in frontline protocols in Singapore, Taiwan, and at St. Jude Children's Research Hospital. Patients carrying these variants experienced significant toxicity and reduced tolerance to MP across treatment protocols. Functionally, all 3 variants led to partial to complete loss of NUDT15 nucleotide diphosphatase activity and negatively influenced protein stability. In particular, the p.G17_V18del variant protein showed extremely low thermostability and was completely void of catalytic activity, thus likely to confer a high risk of thiopurine intolerance. This in-frame deletion was only seen in African and European patients, and is the first NUDT15 risk variant identified in non-Asian, non-Hispanic populations. In conclusion, we discovered 3 novel loss-of-function variants in NUDT15 associated with MP toxicity, enabling more comprehensive pharmacogenetics-based thiopurine dose adjustments across diverse populations.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics*
  17. Li Z, Lee SHR, Chin WHN, Lu Y, Jiang N, Lim EH, et al.
    Blood Adv, 2021 12 14;5(23):5226-5238.
    PMID: 34547766 DOI: 10.1182/bloodadvances.2021004895
    Among the recently described subtypes in childhood B-lymphoblastic leukemia (B-ALL) were DUX4- and PAX5-altered (PAX5alt). By using whole transcriptome RNA sequencing in 377 children with B-ALL from the Malaysia-Singapore ALL 2003 (MS2003) and Malaysia-Singapore ALL 2010 (MS2010) studies, we found that, after hyperdiploid and ETV6-RUNX1, the third and fourth most common subtypes were DUX4 (n = 51; 14%) and PAX5alt (n = 36; 10%). DUX4 also formed the largest genetic subtype among patients with poor day-33 minimal residual disease (MRD; n = 12 of 44). But despite the poor MRD, outcome of DUX4 B-ALL was excellent (5-year cumulative risk of relapse [CIR], 8.9%; 95% confidence interval [CI], 2.8%-19.5% and 5-year overall survival, 97.8%; 95% CI, 85.3%-99.7%). In MS2003, 21% of patients with DUX4 B-ALL had poor peripheral blood response to prednisolone at day 8, higher than other subtypes (8%; P = .03). In MS2010, with vincristine at day 1, no day-8 poor peripheral blood response was observed in the DUX4 subtype (P = .03). The PAX5alt group had an intermediate risk of relapse (5-year CIR, 18.1%) but when IKZF1 was not deleted, outcome was excellent with no relapse among 23 patients. Compared with MS2003, outcome of PAX5alt B-ALL with IKZF1 codeletion was improved by treatment intensification in MS2010 (5-year CIR, 80.0% vs 0%; P = .05). In conclusion, despite its poor initial response, DUX4 B-ALL had a favorable overall outcome, and the prognosis of PAX5alt was strongly dependent on IKZF1 codeletion.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma*
  18. Lu Y, Kham SK, Ariffin H, Oei AM, Lin HP, Tan AM, et al.
    Br. J. Cancer, 2014 Mar 18;110(6):1673-80.
    PMID: 24434428 DOI: 10.1038/bjc.2014.7
    Host germline variations and their potential prognostic importance is an emerging area of interest in paediatric ALL.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics*
  19. Jiang N, Wang L, Xiang X, Li Z, Chiew EKH, Koo YM, et al.
    Br J Clin Pharmacol, 2021 Apr;87(4):1990-1999.
    PMID: 33037681 DOI: 10.1111/bcp.14596
    AIMS: Vincristine (VCR) is a key drug in the successful multidrug chemotherapy for childhood acute lymphoblastic leukaemia (ALL). However, it remains unclear how VCR pharmacokinetics affects its antileukaemic efficacy. The objective of this study is to explore the VCR pharmacokinetic parameters and intracellular VCR levels in an up-front window of Ma-Spore ALL 2010 (MS2010) study.

    METHODS: We randomised 429 children with newly diagnosed ALL to 15-minute vs 3-hour infusion for the first dose of VCR to study if prolonging the first dose of VCR infusion improved response. In a subgroup of 115 B-ALL and 20 T-ALL patients, we performed VCR plasma (n = 135 patients) and intracellular (n = 66 patients) pharmacokinetic studies. The correlations between pharmacokinetic parameters and intracellular VCR levels with early treatment response, final outcome and ABCB1 genotypes were analysed.

    RESULTS: There was no significant difference between 15-minute and 3-hour infusion schedules in median Day 8 peripheral or bone marrow blast response. Plasma VCR pharmacokinetic parameters did not predict outcome. However, in B-ALL, Day 33 minimal residual disease (MRD) negative patients and patients in continuous complete remission had significantly higher median intracellular VCR24h levels (P = .03 and P = .04, respectively). The median VCR24h intracellular levels were similar among the common genetic subtypes of ALL (P = .4). Patients homozygous for wild-type ABCB1 2677GG had significantly higher median intracellular VCR24h (P = .04) than 2677TT.

    CONCLUSION: We showed that in childhood B-ALL, the intracellular VCR24h levels in lymphoblasts affected treatment outcomes. The intracellular VCR24h level was independent of leukaemia subtype but dependent on host ABCB1 G2677T genotype.

    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma
  20. Jackson N, Reddy SC, Harun MH, Quah SH, Low HC
    Br J Haematol, 1997 Jul;98(1):204-9.
    PMID: 9233585
    Retinal changes are common in adult acute leukaemia patients at presentation, but whether they correlate with the risk of subsequent intracranial haemorrhage is unknown. A 4-year study has been carried out in 82 newly-diagnosed acute leukaemia patients, aged 12-77 years, who were studied prospectively for the presence of intra-retinal haemorrhages (IRH), white-centred haemorrhages (WCH), cotton-wool spots (CWS) and macular haemorrhages (MH). Groups with and without these features were compared for their risk of intra-cranial haemorrhage (ICH) within the first 30 d following diagnosis. There was no association between the incidence of ICH and the presence of IRH, WCH or CWS. However, 6/13 of those with MH developed ICH, compared to 6/69 of those without MH (relative risk 5.0, CI 95% [2.03-12.33], P=0.003). The only other identifiable risk factor for ICH was the M3 subtype of AML, but if the four cases of M3-AML were discounted from analysis, MH remained a highly significant risk factor for ICH. Patients with MH should be monitored intensively for the development of ICH, and receive priority in the allocation of platelets where these are in short supply.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications*
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