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  1. Abdul Rasool Hassan B, Yusoff ZB, Bin Othman S
    Asian Pac J Cancer Prev, 2011;12(6):1425-8.
    PMID: 22126475
    INTRODUCTION: Neutropenia, defined as a decrease in the absolute neutrophil count lower than the normal that is < 1500 cell/ ?l, has a detrimental effect on cancer patients' quality of life, also possibly resulting in a reduction in the chemotherapy dose which could lead to an increment in the size of a cancer. There are so many causative factors for neutropenia like hematological disorders, autoimmune diseases and infection, drugs reactions and chemotherapy or radiotherapy. So the main aim of this study is to find the association between chemotherapy drug or regimens, schedule of administration used for treatment of solid cancer diseases with neutropenia onset and severity.

    METHODS: This is an observational retrospective study carried out in a general hospital on 117 solid tumor patients who admitted between January 2003 to December 2006. The main statistical tests used were Chi- square test and Fisher' s Exact test. The significance of the result will be when the P<0.05, while the confidence interval for this study was 95%.

    RESULTS: The highest chemotherapeutic regimen was (5-FU+epirubicin+cyclophosphamide) (47, 40.2%) followed by (gemcitabine+cisplatin) (6, 5.1%) and many others. Majority of the patients receive their chemotherapy schedule of administration was one day schedule (90, 76.9%) followed by more than one day schedule (27, 23.1%).

    CONCLUSION: The doses of these drugs were not high enough to produce a sufficient pharmacological effect to cause bone marrow suppression and lead to neutropenia. Besides the schedule of administration for each drug was long enough to overcome neutropenia also the high uses of granulocyte colony stimulation factor (G-CSF) which will play a major role in reducing the time and severity of neutropenia. All these factors play an important role in giving non- significant association between neutropenia onset and severity with chemotherapeutics drugs and their schedule of administration.

    Matched MeSH terms: Neutropenia/chemically induced*
  2. Kandane-Rathnayake R, Louthrenoo W, Golder V, Luo SF, Wu YJ, Lateef A, et al.
    Rheumatology (Oxford), 2021 Nov 03;60(11):5185-5193.
    PMID: 33693676 DOI: 10.1093/rheumatology/keab217
    OBJECTIVE: The prevalence and associations of leucopenia in SLE remain incompletely understood. We evaluated associations of disease activity and medication use with leucopenia (lymphopenia and neutropenia) in a multinational, prospectively followed SLE cohort.

    METHODS: Data from the Asia Pacific Lupus Collaboration cohort, in which disease activity and medications were prospectively captured from 2013 to 2018, were used. Predictors of lymphopenia (lymphocyte count <0.8 × 109/l) and neutropenia (neutrophil count <1.5 × 109/l) were examined using multiple failure, time-dependent survival analyses.

    RESULTS: Data from 2330 patients and 18 287 visits were analysed. One thousand and eighteen patients (43.7%) had at least one episode of leucopenia; 867 patients (37.2%) had lymphopenia, observed in 3065 (16.8%) visits, and 292 (12.5%) patients had neutropenia, in 622 (3.4%) visits. After multivariable analyses, lymphopenia was associated with overall disease activity, ESR, serology, prednisolone, AZA, MTX, tacrolimus, CYC and rituximab use. MTX and ciclosporin were negatively associated with neutropenia. Lupus low disease activity state was negatively associated with both lymphopenia and neutropenia.

    CONCLUSION: Both lymphopenia and neutropenia were common in SLE patients but were differentially associated with disease and treatment variables. Lymphopenia and neutropenia should be considered independently in studies in SLE.

    Matched MeSH terms: Neutropenia/chemically induced*
  3. Baskaran ND, Gan GG, Kamarulzaman A, Sam IC
    Int J Infect Dis, 2007 Nov;11(6):513-7.
    PMID: 17459753
    OBJECTIVES: This study was initiated to determine the local profile of blood culture isolates and antibiotic sensitivities in febrile neutropenic patients following chemotherapy, and to establish if any modifications to treatment guidelines are necessary.
    DESIGN: A total of 116 episodes of febrile neutropenia admitted to the adult hematology ward at a university medical center in Malaysia were studied retrospectively from January 2004 to January 2005.
    RESULTS: The study showed 43.1% of febrile neutropenic episodes had established bacteremia. Gram-negative bacteria accounted for 60.3% of isolates. Sensitivities of Gram-negative bacteria to the antibiotics recommended in the Infectious Diseases Society of America (IDSA) guidelines were 86.1-97.2%. Coagulase-negative staphylococci were the most common Gram-positive organisms isolated (23.3%). The majority of these were methicillin-resistant.
    CONCLUSIONS: Carbapenem monotherapy, as recommended in the 2002 IDSA guidelines, is effective treatment for the infections most often encountered at our center. Combination therapy with an aminoglycoside should be considered when using ceftazidime, cefepime or piperacillin-tazobactam, particularly in high-risk patients. Vancomycin should be used if a Gram-positive organism is suspected or isolated.
    Matched MeSH terms: Neutropenia/chemically induced*
  4. Hassan BA, Yusoff ZB, Othman SB
    Asian Pac J Cancer Prev, 2009 Oct-Dec;10(4):641-4.
    PMID: 19827886
    INTRODUCTION: Neutropenia has a detrimental effect on cancer patients' quality of life, also possibly resulting in a reduction in the chemotherapy dose which could lead to an increment in the size of a cancer. The main danger associated with neutropenia is the risk of bacterial, fungal or viral infection, which may lead to patient death. Treatment including granulocyte-colony stimulating factors (G-CSF, filgrastim) so as to increase the body immunity is given to neutropenic patients with no infection i.e., absence of fever. However, when infection is present, antibiotics such as ceftazidime, imipenem and vancomycin need to be used.

    OBJECTIVE: The aim of this study was to find the association between neutropenia severity and treatment with filgrastim (Neupogen) alone or in combination with antibiotics in solid cancer patients.

    METHODS: This is an observational retrospective study on 117 cases suffering from neutropenia after chemotherapy administration. The patients were admitted to a government hospital for cancer treatment between the years 2003-2006. The types of data collected were categorical and not normally distributed, covering demography, chemotherapy, severity of neutropenia (classified on absolute neutrophil count into mild, moderate and severe) and treatment of neutropenia, either filgrastim (Neupogen) alone or in combination with antibiotics. Statistical tests used were the Chi-square test, Fisher's exact test and logistic regression.

    RESULTS: The majority (69.2%) of the patients were treated with filgrastim (81) alone, only 30.8% receiving the combination. Significant associations between both treatments and neutropenia severity. Both Chi-square and Fisher's exact tests showed P= 0.001. Logistic regression showed that filgrastim is the major treatment for severe neutropenic patients since the result showed an infinity (E) and P= 0.001 for filgrastim alone more than its combination with antibiotic.

    CONCLUSION: The use of filgrastim is highly associated with treatment of severe neutropenia in solid cancer patients who received chemotherapy. So filgrastim is considered as the drug of choice in the presence of severe neutropenic cases.
    Matched MeSH terms: Neutropenia/chemically induced
  5. Jada SR, Lim R, Wong CI, Shu X, Lee SC, Zhou Q, et al.
    Cancer Sci, 2007 Sep;98(9):1461-7.
    PMID: 17627617
    The objectives of the present study were (i) to study the pharmacogenetics of UGT1A1*6, UGT1A1*28 and ABCG2 c.421C>A in three distinct healthy Asian populations (Chinese, Malays and Indians), and (ii) to investigate the polygenic influence of these polymorphic variants in irinotecan-induced neutropenia in Asian cancer patients. Pharmacokinetic and pharmacogenetic analyses were done after administration of irinotecan as a 90-min intravenous infusion of 375 mg/m(2) once every 3 weeks (n = 45). Genotypic-phenotypic correlates showed a non-significant influence of UGT1A1*28 and ABCG2 c.421C>A polymorphisms on the pharmacokinetics of SN-38 (P > 0.05), as well as severity of neutropenia (P > 0.05). Significantly higher exposure levels to SN-38 (P = 0.018), lower relative extent of glucuronidation (REG; P = 0.006) and higher biliary index (BI; P = 0.003) were found in cancer patients homozygous for the UGT1A1*6 allele compared with patients harboring the reference genotype. The mean absolute neutrophil count (ANC) was 85% lower and the prevalence of grade 4 neutropenia (ANC < or = 500/microL) was 27% in patients homozygous for UGT1A1*6 compared with the reference group. Furthermore, the presence of the UGT1A1*6 allele was associated with an approximately 3-fold increased risk of developing severe grade 4 neutropenia compared with patients harboring the reference genotype. These exploratory findings suggest that homozygosity for UGT1A1*6 allele may be associated with altered SN-38 disposition and may increase the risk of severe neutropenia in Asian cancer patients, particularly in the Chinese cancer patients who comprised 80% (n = 36) of the patient population in the present study.
    Matched MeSH terms: Neutropenia/chemically induced*
  6. Phua CE, Bustam AZ, Yusof MM, Saad M, Yip CH, Taib NA, et al.
    Asian Pac J Cancer Prev, 2012;13(9):4623-6.
    PMID: 23167391
    BACKGROUND: The risk of treatment-related death (TRD) and febrile neutropaenia (FN) with adjuvant taxane- based chemotherapy for early breast cancer is unknown in Malaysia despite its widespread usage in recent years. This study aims to determine these rates in patients treated in University Malaya Medical Centre (UMMC).

    PATIENTS AND METHODS: Patients who were treated with adjuvant taxane-based chemotherapy for early breast cancer stages I, II or III from 2007-2011 in UMMC were identified from our UMMC Breast Cancer Registry. The TRD and FN rates were then determined retrospectively from medical records. TRD was defined as death occurring during or within 30 days of completing chemotherapy as a consequence of the chemotherapy treatment. FN was defined as an oral temperature >38.5°C or two consecutive readings of >38.0°C for 2 hours and an absolute neutrophil count <0.5x109/L, or expected to fall below 0.5x109/L.

    RESULTS: A total of 622 patients received adjuvant chemotherapy during this period. Of these patients 209 (33.6%) received taxane-based chemotherapy. 4 taxane-based regimens were used namely the FEC-D, TC, TAC and AC-PCX regimens. The commonest regimen employed was the FEC-D regimen accounting for 79.9% of the patients. The FN rate was 10% and there was no TRD.

    CONCLUSION: Adjuvant taxane-based chemotherapy in UMMC for early breast cancer has a FN rate of 10%. Primary prophylactic G-CSF should be considered for patients with any additional risk factor for FN.

    Matched MeSH terms: Neutropenia/chemically induced
  7. Hor SY, Lee SC, Wong CI, Lim YW, Lim RC, Wang LZ, et al.
    Pharmacogenomics J, 2008 Apr;8(2):139-46.
    PMID: 17876342
    Previously studied candidate genes have failed to account for inter-individual variability of docetaxel and doxorubicin disposition and effects. We genotyped the transcriptional regulators of CYP3A and ABCB1 in 101 breast cancer patients from 3 Asian ethnic groups, that is, Chinese, Malays and Indians, in correlation with the pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin. While there was no ethnic difference in docetaxel and doxorubicin pharmacokinetics, ethnic difference in docetaxel- (ANOVA, P=0.001) and doxorubicin-induced (ANOVA, P=0.003) leukocyte suppression was observed, with Chinese and Indians experiencing greater degree of docetaxel-induced myelosuppression than Malays (Bonferroni, P=0.002, P=0.042), and Chinese experiencing greater degree of doxorubicin-induced myelosuppression than Malays and Indians (post hoc Bonferroni, P=0.024 and 0.025). Genotyping revealed both PXR and CAR to be well conserved; only a PXR 5'-untranslated region polymorphism (-24381A>C) and a silent CAR variant (Pro180Pro) were found at allele frequencies of 26 and 53%, respectively. Two non-synonymous variants were identified in HNF4alpha (Met49Val and Thr130Ile) at allele frequencies of 55 and 1%, respectively, with the Met49Val variant associated with slower neutrophil recovery in docetaxel-treated patients (ANOVA, P=0.046). Interactions were observed between HNF4alpha Met49Val and CAR Pro180Pro, with patients who were wild type for both variants experiencing least docetaxel-induced neutropenia (ANOVA, P=0.030). No other significant genotypic associations with pharmacokinetics or pharmacodynamics of either drug were found. The PXR-24381A>C variants were significantly more common in Indians compared to Chinese or Malays (32/18/21%, P=0.035) Inter-individual and inter-ethnic variations of docetaxel and doxorubicin pharmacokinetics or pharmacodynamics exist, but genotypic variability of the transcriptional regulators PAR, CAR and HNF4alpha cannot account for this variability.
    Matched MeSH terms: Neutropenia/chemically induced
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