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1. Mould DR, Baumann A, Kuhlmann J, Keating MJ, Weitman S, Hillmen P, Brettman LR, Reif S, Bonate PL: Population pharmacokinetics-pharmacodynamics of alemtuzumab (Campath) in patients with chronic lymphocytic leukaemia and its link to treatment response. Br J Clin Pharmacol; 2007 Sep;64(3):278-91

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Population pharmacokinetics-pharmacodynamics of alemtuzumab (Campath) in patients with chronic lymphocytic leukaemia and its link to treatment response.
  • AIMS: To characterize alemtuzumab pharmacokinetics and its exposure-response relationship with white blood cell (WBC) count in patients with B-cell chronic lymphocytic leukaemia (CLL).
  • METHODS: Nonlinear mixed effects models were used to characterize plasma concentration-time data and WBC count-time data from 67 patients.
  • Logistic regression was used to relate summary measures of drug exposure to tumour response.
  • RESULTS: Alemtuzumab pharmacokinetics were best characterized by a two-compartment model with nonlinear elimination where V(max) (microg h(-1)) was [1020 x (WBC count/10 x 10(9) l(-1))(0.194)], K(m) was 338 microg l(-1), V(1) was 11.3 l, Q was 1.05 l h(-1) and V(2) was 41.5 l.
  • The reduction in WBC over time was modelled by a stimulatory loss indirect response model with values of 18.2 for E(max), 306 microg l(-1) for EC(50), 1.56 x 10(9) cells l(-1) h(-1) for K(in) and 0.029 per h for K(out).
  • CONCLUSIONS: Alemtuzumab displayed time- and concentration-dependent pharmacokinetics with large interpatient variability, both in pharmacokinetics and pharmacodynamics, which was probably reflective of differences in tumour burden among patients.
  • A direct relationship between maximal trough concentrations and clinical outcomes was observed, with increasing alemtuzumab exposure resulting in a greater probability of positive tumour response.
  • [MeSH-major] Antibodies, Monoclonal / pharmacokinetics. Antineoplastic Agents / pharmacokinetics. Immunoglobulin G / blood. Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy. Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
  • [MeSH-minor] Adult. Aged. Antibodies, Monoclonal, Humanized. Antibodies, Neoplasm / pharmacology. Dose-Response Relationship, Drug. Female. Humans. Leukocyte Count. Logistic Models. Male. Middle Aged. Models, Biological. Nonlinear Dynamics

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  • (PMID = 17506867.001).
  • [ISSN] 0306-5251
  • [Journal-full-title] British journal of clinical pharmacology
  • [ISO-abbreviation] Br J Clin Pharmacol
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antibodies, Neoplasm; 0 / Antineoplastic Agents; 0 / Immunoglobulin G; 3A189DH42V / alemtuzumab
  • [Other-IDs] NLM/ PMC2000651
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2. Hawwa AF, Collier PS, Millership JS, McCarthy A, Dempsey S, Cairns C, McElnay JC: Population pharmacokinetic and pharmacogenetic analysis of 6-mercaptopurine in paediatric patients with acute lymphoblastic leukaemia. Br J Clin Pharmacol; 2008 Dec;66(6):826-37
Hazardous Substances Data Bank. MERCAPTOPURINE .

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  • [Title] Population pharmacokinetic and pharmacogenetic analysis of 6-mercaptopurine in paediatric patients with acute lymphoblastic leukaemia.
  • AIMS: To investigate the population pharmacokinetics of 6-mercaptopurine (6-MP) active metabolites in paediatric patients with acute lymphoblastic leukaemia (ALL) and examine the effects of various genetic polymorphisms on the disposition of these metabolites.
  • METHODS: Data were collected prospectively from 19 paediatric patients with ALL (n = 75 samples, 150 concentrations) who received 6-MP maintenance chemotherapy (titrated to a target dose of 75 mg m(-2) day(-1)).
  • Population pharmacokinetic analysis was performed with the nonlinear mixed effects modelling program (nonmem) to determine the population mean parameter estimate of clearance for the active metabolites.
  • RESULTS: The developed model revealed considerable interindividual variability (IIV) in the clearance of 6-MP active metabolites [6-thioguanine nucleotides (6-TGNs) and 6-methylmercaptopurine nucleotides (6-mMPNs)].
  • Body surface area explained a significant part of 6-TGNs clearance IIV when incorporated in the model (IIV reduced from 69.9 to 29.3%).
  • The other genetic covariates tested were not statistically significant and therefore were not included in the final model.
  • CONCLUSIONS: The developed pharmacokinetic model (if successful at external validation) would offer a more rational dosing approach for 6-MP than the traditional empirical method since it combines the current practice of using body surface area in 6-MP dosing with a pharmacogenetically guided dosing based on TPMT genotype.
  • [MeSH-major] 6-Mercaptopurine / analogs & derivatives. Antimetabolites, Antineoplastic / pharmacokinetics. Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics. Methyltransferases / pharmacokinetics. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • [MeSH-minor] Adolescent. Child. Child, Preschool. Dose-Response Relationship, Drug. Drug Administration Schedule. Female. Genotype. Humans. Male. Metabolic Clearance Rate / genetics. Models, Biological. Pharmacogenetics. Prospective Studies

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  • (PMID = 18823306.001).
  • [ISSN] 1365-2125
  • [Journal-full-title] British journal of clinical pharmacology
  • [ISO-abbreviation] Br J Clin Pharmacol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; 6V404DV25O / 6-methylthiopurine; E7WED276I5 / 6-Mercaptopurine; EC 2.1.1.- / Methyltransferases; EC 2.1.1.67 / thiopurine methyltransferase
  • [Other-IDs] NLM/ PMC2675766
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3. Rubnitz JE, Inaba H, Dahl G, Ribeiro RC, Bowman WP, Taub J, Pounds S, Razzouk BI, Lacayo NJ, Cao X, Meshinchi S, Degar B, Airewele G, Raimondi SC, Onciu M, Coustan-Smith E, Downing JR, Leung W, Pui CH, Campana D: Minimal residual disease-directed therapy for childhood acute myeloid leukaemia: results of the AML02 multicentre trial. Lancet Oncol; 2010 Jun;11(6):543-52
Hazardous Substances Data Bank. ETOPOSIDE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Minimal residual disease-directed therapy for childhood acute myeloid leukaemia: results of the AML02 multicentre trial.
  • BACKGROUND: We sought to improve outcome in patients with childhood acute myeloid leukaemia (AML) by applying risk-directed therapy that was based on genetic abnormalities of the leukaemic cells and measurements of minimal residual disease (MRD) done by flow cytometry during treatment.
  • METHODS: From Oct 13, 2002, to June 19, 2008, 232 patients with de-novo AML (n=206), therapy-related or myelodysplasia-related AML (n=12), or mixed-lineage leukaemia (n=14) were enrolled at eight centres.
  • The primary aim of the study was to compare the incidence of MRD positivity of the high-dose group and the low-dose group at day 22 of induction 1.
  • Induction 2 consisted of ADE with or without gemtuzumab ozogamicin (GO anti-CD33 monoclonal antibody); consolidation therapy included three additional courses of chemotherapy or haematopoietic stem-cell transplantation (HSCT).
  • Both MRD and genetic abnormalities at diagnosis were used to determine the final risk classification.
  • Low-risk patients (n=68) received five courses of chemotherapy, whereas high-risk patients (n=79), and standard-risk patients (n=69) with matched sibling donors, were eligible for HSCT (done for 48 high-risk and eight standard-risk patients).
  • All 230 randomised patients were analysed for the primary endpoint.
  • Other analyses were limited to the 216 patients with AML, excluding those with mixed-lineage leukaemia.
  • Induction failures included two deaths from toxic effects and ten cases of resistant leukaemia.
  • The introduction of high-dose versus low-dose cytarabine did not significantly lower the rate of MRD-positivity after induction 1 (34%vs 42%, p=0.17).
  • The 6-month cumulative incidence of grade 3 or higher infection was 79.3% (SE 4.0) for patients in the high-dose group and 75.5% (4.2) for the low-dose group.
  • 3-year event-free survival and overall survival were 63.0% (SE 4.1) and 71.1% (3.8), respectively.
  • 80% (155 of 193) of patients achieved MRD of less than 0.1% after induction 2, and the cumulative incidence of relapse for this group was 17% (SE 3).
  • INTERPRETATION: Our findings suggest that the use of targeted chemotherapy and HSCT, in the context of a comprehensive risk-stratification strategy based on genetic features and MRD findings, can improve outcome in patients with childhood AML.
  • FUNDING: National Institutes of Health and American Lebanese Syrian Associated Charities (ALSAC).
  • [MeSH-major] Leukemia, Myeloid, Acute / drug therapy. Leukemia, Myeloid, Acute / pathology
  • [MeSH-minor] Adolescent. Aminoglycosides / therapeutic use. Antibodies, Monoclonal / therapeutic use. Antibodies, Monoclonal, Humanized. Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Child. Child, Preschool. Cytarabine / administration & dosage. Cytogenetic Analysis. Daunorubicin / administration & dosage. Disease-Free Survival. Etoposide / administration & dosage. Female. Flow Cytometry. Humans. Infant. Infant, Newborn. Male. Neoplasm, Residual. Remission Induction. Survival Rate. Young Adult

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  • [Copyright] Copyright 2010 Elsevier Ltd. All rights reserved.
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  • (PMID = 20451454.001).
  • [ISSN] 1474-5488
  • [Journal-full-title] The Lancet. Oncology
  • [ISO-abbreviation] Lancet Oncol.
  • [Language] eng
  • [Databank-accession-numbers] ClinicalTrials.gov/ NCT00136084
  • [Grant] United States / NCI NIH HHS / CA / P30 CA021765; United States / NCI NIH HHS / CA / R01 CA115422; United States / NCI NIH HHS / CA / R01 CA115422-02
  • [Publication-type] Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Aminoglycosides; 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 04079A1RDZ / Cytarabine; 6PLQ3CP4P3 / Etoposide; 93NS566KF7 / gemtuzumab; ZS7284E0ZP / Daunorubicin; DAV regimen
  • [Other-IDs] NLM/ NIHMS319127; NLM/ PMC3171799
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4. Pullarkat V, Veliz L, Chang K, Mohrbacher A, Teotico AL, Forman SJ, Slovak ML: Therapy-related, mixed-lineage leukaemia translocation-positive, monoblastic myeloid sarcoma of the uterus. J Clin Pathol; 2007 May;60(5):562-4
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  • [Title] Therapy-related, mixed-lineage leukaemia translocation-positive, monoblastic myeloid sarcoma of the uterus.
  • Myeloid sarcomas are tumour masses of myeloid leukaemic cells at extramedullary sites.
  • These tumours can, on occasion, occur without concurrent or antecedent leukaemia.
  • An unusual case of therapy-related acute myeloid leukaemia (t-AML) presenting as isolated monoblastic myeloid sarcoma of the uterus in a patient who had received adjuvant chemotherapy for breast cancer is presented.
  • Fluorescence in situ hybridisation analysis performed on paraffin-wax-embedded tumour tissue revealed a mixed-lineage leukaemia (MLL) gene rearrangement, supporting the association of this malignancy with prior chemotherapy.
  • This case illustrates that t-AML can rarely present as isolated extramedullary tumours, and the detection of specific chromosomal abnormalities in these myeloid sarcomas can be useful for risk assessment and guiding definitive therapy.

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  • (PMID = 17513515.001).
  • [ISSN] 0021-9746
  • [Journal-full-title] Journal of clinical pathology
  • [ISO-abbreviation] J. Clin. Pathol.
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / P01 CA030206; United States / NCI NIH HHS / CA / 2 P01 CA030206-24A1; United States / NCI NIH HHS / CA / 5P30 CA33572
  • [Publication-type] Case Reports; Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] England
  • [Other-IDs] NLM/ PMC1994540
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5. Pieters R, Schrappe M, De Lorenzo P, Hann I, De Rossi G, Felice M, Hovi L, LeBlanc T, Szczepanski T, Ferster A, Janka G, Rubnitz J, Silverman L, Stary J, Campbell M, Li CK, Mann G, Suppiah R, Biondi A, Vora A, Valsecchi MG: A treatment protocol for infants younger than 1 year with acute lymphoblastic leukaemia (Interfant-99): an observational study and a multicentre randomised trial. Lancet; 2007 Jul 21;370(9583):240-50
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  • [Title] A treatment protocol for infants younger than 1 year with acute lymphoblastic leukaemia (Interfant-99): an observational study and a multicentre randomised trial.
  • BACKGROUND: Acute lymphoblastic leukaemia in infants younger than 1 year is rare, and infants with the disease have worse outcomes than do older children.
  • We initiated an international study to investigate the effects of a new hybrid treatment protocol with elements designed to treat both acute lymphoblastic leukaemia and acute myeloid leukaemia, and to identify any prognostic factors for outcome in infants.
  • We also did a randomised trial to establish the value of a late intensification course.
  • Eligible patients were stratified for risk according to their peripheral blood response to a 7-day prednisone prophase, and then given a hybrid regimen based on the standard protocol for acute lymphoblastic leukaemia, with some elements designed for treatment of acute myeloid leukaemia.
  • Before the maintenance phase, a subset of patients in complete remission were randomly assigned to receive either standard treatment or a more intensive chemotherapy course with high-dose cytarabine and methotrexate.
  • The primary outcomes were event-free survival (EFS) for the initial cohort of patients and disease-free survival (DFS) for the patients randomly assigned to a treatment group.
  • FINDINGS: In the 482 enrolled patients who underwent hybrid treatment, 260 (58%) were in complete remission at a median follow-up of 38 (range 1-78) months, and EFS at 4 years was 47.0% (SE 2.6, 95% CI 41.9-52.1).
  • Of 445 patients in complete remission after 5 weeks of induction treatment, 191 were randomised: 95 patients to receive a late intensification course, and 96 to a control group.
  • At a median follow-up of 42 (range 1-73) months, 60 patients in the treatment group and 57 controls were disease-free.
  • DFS at 4 years did not differ between the two groups (60.9% [SE 5.2] for treatment group vs 57.0% [5.5] for controls; p=0.81).
  • During the intensification phase, of 71 patients randomly assigned to the treatment group, and for whom toxicity data were available, 35 (49%) had infections, 21 (30%) patients had mucositis, 22 (31%) patients had toxic effects on the liver, and 2 (3%) had neurotoxicity.
  • All types of rearrangements in the (mixed lineage leukaemia) MLL gene, very high white blood cell count, age of younger than 6 months, and a poor response to the prednisone prophase were independently associated with inferior outcomes.
  • INTERPRETATION: Patients treated with our hybrid protocol, and especially those who responded poorly to prednisone, had higher EFS than most reported outcomes for treatment of infant ALL.
  • Delayed intensification of chemotherapy did not benefit patients.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Myeloid, Acute / drug therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy

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  • [CommentIn] Lancet. 2007 Jul 21;370(9583):198-200 [17658376.001]
  • (PMID = 17658395.001).
  • [ISSN] 1474-547X
  • [Journal-full-title] Lancet (London, England)
  • [ISO-abbreviation] Lancet
  • [Language] eng
  • [Databank-accession-numbers] ClinicalTrials.gov/ NCT00015873; ISRCTN/ ISRCTN24251487
  • [Grant] United Kingdom / Medical Research Council / / G0300130
  • [Publication-type] Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; VB0R961HZT / Prednisone; YL5FZ2Y5U1 / Methotrexate
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6. Yamamura T, Ueda M, Psarras K, Suwa T, Watanaabe Y, Kameyama N, Tanabe M, Imamura H, Kitajima M: Immunosuppressive and anticancer effect of a mammalian ribonuclease that targets high-affinity interleukin-2-receptors. Eur J Surg; 2002;168(1):49-54
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  • [Title] Immunosuppressive and anticancer effect of a mammalian ribonuclease that targets high-affinity interleukin-2-receptors.
  • MATERIAL: Human lymphocytes isolated from healthy histoincompatible donors in mixed lymphocyte cultures or stimulated with phytohemagglutinin (PHA) to promote IL-2Ralpha expression.
  • INTERVENTIONS: Bovine RNaseA was chemically conjugated to 7G7B6, a monoclonal antibody to the alpha-chain of human IL-2 receptors, and several concentrations of the conjugates were added to the lymphocyte cultures.
  • RESULTS: 7G7B6-RNaseA dose-dependently inhibited cell proliferation in PHA-stimulated human lymphocytes at a 50% inhibitory concentration (IC50) of 2 x 10(-7) M. whereas RNase alone and RNase plus antibody had no inhibitory effect.
  • 7G7B6-RNaseA also dose-dependently inhibited the human mixed lymphocyte reaction at an IC50 of 2 x 10(-6) M, whereas RNase alone did not.
  • The conjugate also inhibited cell proliferation in MJ cells, a cell line that is infected with HTLV-I and overexpresses the high-affinity IL-2 receptor, at an IC50 of 5 x 10(-7) M.
  • However the conjugate had no inhibitory effect on the IL-2 receptor non-expressing human T-cell lymphoblastic leukaemia cell lines MOLT-4F or MT-1.
  • CONCLUSION: 7G7B6-RNaseA can inhibit cell proliferation in antigen- or mitogen-stimulated lymphocytes that overexpress high-affinity IL-2 receptors, and it may be safer than conventional chemotherapy or immunotoxins in the treatment of transplant rejection, certain lymphocytic malignancies, and other IL-2R-associated diseases, because it contains a mammalian cytotoxic enzyme.
  • [MeSH-major] Antineoplastic Agents / pharmacology. Immunosuppressive Agents / pharmacology. Receptors, Interleukin-2 / drug effects. Ribonuclease, Pancreatic / pharmacology
  • [MeSH-minor] Animals. Cattle. Cell Division / drug effects. Humans. Lymphocyte Culture Test, Mixed. Lymphocytes / drug effects. Mice

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  • (PMID = 12022372.001).
  • [ISSN] 1102-4151
  • [Journal-full-title] The European journal of surgery = Acta chirurgica
  • [ISO-abbreviation] Eur J Surg
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Norway
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Immunosuppressive Agents; 0 / Receptors, Interleukin-2; EC 3.1.27.5 / Ribonuclease, Pancreatic
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7. Aumente D, Buelga DS, Lukas JC, Gomez P, Torres A, García MJ: Population pharmacokinetics of high-dose methotrexate in children with acute lymphoblastic leukaemia. Clin Pharmacokinet; 2006;45(12):1227-38
Hazardous Substances Data Bank. METHOTREXATE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Population pharmacokinetics of high-dose methotrexate in children with acute lymphoblastic leukaemia.
  • OBJECTIVE: To develop and a priori validate a methotrexate population pharmacokinetic model in children with acute lymphoblastic leukaemia (ALL), receiving high-dose methotrexate followed by folinic acid rescue, identifying the covariates that could explain part of the pharmacokinetic variability of methotrexate.
  • METHODS: The study was carried out in 49 children (aged 6 months to 17 years) who received high-dose methotrexate (3 g/m(2) per course) in long-term treatment.
  • In an index group (37 individuals; 1236 methotrexate plasma concentrations), a population pharmacokinetic model was developed using a nonlinear mixed-effects model.
  • Age, sex, total bodyweight (TBW), height, body surface area, lowest urine pH during infusion, serum creatinine, ALT, AST, folinic acid dose and length of rescue were analysed as possible covariates.
  • For children aged < or =10 years: CL (L/h) = 0.287 .
  • TBW, and for children aged >10 years: CL (L/h) = 0.149 .
  • From the base to the final model, the inter-individual variabilities for CL and V(1) were significantly reduced in both age groups (30-50%).
  • CONCLUSION: A methotrexate population pharmacokinetic model has been developed for ALL children.
  • The proposed model could be used in Bayesian algorithms with a limited sampling strategy to estimate the systemic exposure of individual patients to methotrexate and adapt both folinic acid rescue and methotrexate dosing accordingly.
  • [MeSH-major] Methotrexate / pharmacokinetics. Models, Biological. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • [MeSH-minor] Adolescent. Age Factors. Alanine Transaminase / blood. Antimetabolites, Antineoplastic / adverse effects. Antimetabolites, Antineoplastic / pharmacokinetics. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Aspartate Aminotransferases / blood. Bayes Theorem. Body Weight. Child. Child, Preschool. Creatinine / blood. Dose-Response Relationship, Drug. Female. Humans. Infant. Infusions, Intravenous. Leucovorin / administration & dosage. Male. Metabolic Clearance Rate. Monte Carlo Method. Treatment Outcome. Vitamin B Complex / administration & dosage

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  • (PMID = 17112298.001).
  • [ISSN] 0312-5963
  • [Journal-full-title] Clinical pharmacokinetics
  • [ISO-abbreviation] Clin Pharmacokinet
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article
  • [Publication-country] Switzerland
  • [Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; 12001-76-2 / Vitamin B Complex; AYI8EX34EU / Creatinine; EC 2.6.1.1 / Aspartate Aminotransferases; EC 2.6.1.2 / Alanine Transaminase; Q573I9DVLP / Leucovorin; YL5FZ2Y5U1 / Methotrexate
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8. Widmer N, Decosterd LA, Leyvraz S, Duchosal MA, Rosselet A, Debiec-Rychter M, Csajka C, Biollaz J, Buclin T: Relationship of imatinib-free plasma levels and target genotype with efficacy and tolerability. Br J Cancer; 2008 May 20;98(10):1633-40
Hazardous Substances Data Bank. IMATINIB MESYLATE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Imatinib has revolutionised the treatment of chronic myeloid leukaemia (CML) and gastrointestinal stromal tumours (GIST).
  • Using a nonlinear mixed effects population model, individual estimates of pharmacokinetic parameters were derived and used to estimate imatinib exposure (area under the curve, AUC) in 58 patients.
  • Associations between AUC (or clearance) and response or incidence of side effects were explored by logistic regression analysis.
  • Both total (in GIST) and free drug exposure (in CML and GIST) correlated with the occurrence and number of side effects (e.g. odds ratio 2.7+/-0.6 for a two-fold free AUC increase in GIST; P<0.001).
  • Higher free AUC also predicted a higher probability of therapeutic response in GIST (odds ratio 2.6+/-1.1; P=0.026) when taking into account tumour KIT genotype (strongest association in patients harbouring exon 9 mutation or wild-type KIT, known to decrease tumour sensitivity towards imatinib).
  • Our findings represent additional arguments to further evaluate the usefulness of individualizing imatinib prescription based on a therapeutic drug monitoring programme, possibly associated with target genotype profiling of patients.
  • [MeSH-major] Antineoplastic Agents / blood. Antineoplastic Agents / pharmacology. Gastrointestinal Stromal Tumors / drug therapy. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Piperazines / blood. Piperazines / pharmacology. Protein-Tyrosine Kinases / antagonists & inhibitors. Pyrimidines / blood. Pyrimidines / pharmacology
  • [MeSH-minor] Adult. Aged. Area Under Curve. Benzamides. Female. Genotype. Humans. Imatinib Mesylate. Logistic Models. Male. Middle Aged. Multivariate Analysis. Odds Ratio. Protein Kinase Inhibitors / blood. Protein Kinase Inhibitors / pharmacology. Treatment Outcome

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  • (PMID = 18475296.001).
  • [ISSN] 1532-1827
  • [Journal-full-title] British journal of cancer
  • [ISO-abbreviation] Br. J. Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Piperazines; 0 / Protein Kinase Inhibitors; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.1 / Protein-Tyrosine Kinases
  • [Other-IDs] NLM/ PMC2391118
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9. Jurado M, Deeg H, Gooley T, Anasetti C, Chauncey T, Flowers M, Myerson D, Storb R, Appelbaum F: Haemopoietic stem cell transplantation for advanced polycythaemia vera or essential thrombocythaemia. Br J Haematol; 2001 Feb;112(2):392-6
NCI CPTC Antibody Characterization Program. NCI CPTC Antibody Characterization Program .

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  • HSCT was performed because of progression to the spent phase of the disease with myelofibrosis and splenomegaly in 10 patients and evolution into a myelodysplastic syndrome (MDS) or acute myelogenous leukaemia (AML) in nine patients.
  • The interval from diagnosis to HSCT was 77-300 months (median 170).
  • Eleven patients received a transplant from a related, and eight from an unrelated, donor following conditioning with chemotherapy only or chemotherapy plus total body irradiation regimens.
  • Twelve patients are surviving 5-116 months (median 41) after transplant, 10 in continued complete remission, one in haematological remission with residual marrow fibrosis and one with mixed haemopoietic chimaerism currently receiving therapy with interferon.
  • Seven patients (six with AML/MDS and one with myelofibrosis) died of transplant-related complications.
  • These data show that HSCT can provide curative therapy for patients with PV and ET with advanced disease.
  • [MeSH-minor] Adult. Disease-Free Survival. Female. Humans. Male. Middle Aged. Regression Analysis. Remission Induction. Retrospective Studies. Splenectomy. Statistics, Nonparametric

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  • (PMID = 11167837.001).
  • [ISSN] 0007-1048
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA18029; United States / NCI NIH HHS / CA / CA87948; United States / NHLBI NIH HHS / HL / HL36444
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] England
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10. Gaspar HB, Parsley KL, Howe S, King D, Gilmour KC, Sinclair J, Brouns G, Schmidt M, Von Kalle C, Barington T, Jakobsen MA, Christensen HO, Al Ghonaium A, White HN, Smith JL, Levinsky RJ, Ali RR, Kinnon C, Thrasher AJ: Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped gammaretroviral vector. Lancet; 2004 Dec 18-31;364(9452):2181-7
The Lens. Cited by Patents in .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped gammaretroviral vector.
  • BACKGROUND: X-linked severe combined immunodeficiency (SCID-X1) is caused by mutations in the common cytokine-receptor gamma chain (gamma(c)), resulting in disruption of development of T lymphocytes and natural-killer cells.
  • Allogeneic bone-marrow transplantation is successful if HLA-matched family donors are available, but HLA-mismatched procedures are associated with substantial morbidity and mortality.
  • We investigated the application of somatic gene therapy by use of a gibbon-ape-leukaemia-virus pseudotyped gammaretroviral vector.
  • Autologous CD34-positive haemopoietic bone-marrow stem cells were transduced ex vivo and returned to the patients without preceding cytoreductive chemotherapy.
  • FINDINGS: All patients have shown substantial improvements in clinical and immunological features, and prophylactic medication could be withdrawn in two.
  • Where assessable, humoral immunity, in terms of antibody production, was also restored and associated with increasing rates of somatic mutation in immunoglobulin genes.
  • INTERPRETATION: Gene therapy for SCID-X1 is a highly effective strategy for restoration of functional cellular and humoral immunity.
  • [MeSH-major] Genetic Diseases, X-Linked / therapy. Genetic Therapy. Severe Combined Immunodeficiency / therapy
  • [MeSH-minor] Antigens, CD34 / analysis. Bone Marrow Cells / immunology. Bone Marrow Transplantation. Child, Preschool. Gammaretrovirus. Gene Transfer Techniques. Genetic Vectors. Humans. Immunity. Immunoglobulins / blood. Infant. Interleukin Receptor Common gamma Subunit. Lymphocyte Activation. Lymphocyte Culture Test, Mixed. Mutation. Receptors, Interleukin-7 / genetics. T-Lymphocytes / immunology. Transduction, Genetic


11. Chen X, Regn S, Raffegerst S, Kolb HJ, Roskrow M: Interferon alpha in combination with GM-CSF induces the differentiation of leukaemic antigen-presenting cells that have the capacity to stimulate a specific anti-leukaemic cytotoxic T-cell response from patients with chronic myeloid leukaemia. Br J Haematol; 2000 Nov;111(2):596-607
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  • [Title] Interferon alpha in combination with GM-CSF induces the differentiation of leukaemic antigen-presenting cells that have the capacity to stimulate a specific anti-leukaemic cytotoxic T-cell response from patients with chronic myeloid leukaemia.
  • Although interferon alpha (IFN-alpha) is able to induce haematological remission in 60-80% of patients with chronic myeloid leukaemia (CML) in early chronic phase, major cytogenetic remissions are only achievable in 30-40%.
  • Recent clinical data suggest that the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) to IFN-alpha therapy can significantly improve the cytogenetic response in some patients, although the mechanism remains unknown.
  • After 7 d, the number of cells exhibiting typical antigen-presenting cell (APC) morphology was equal in both groups, and fluorescence in situ hybridization (FISH) analysis confirmed that the APCs generated with GM/IFN-alpha were of leukaemic origin.
  • Phenotypically, both sets of APCs expressed typical surface markers; however, CD86, CD83, CD11c, HLA-ABC and HLA-DR expression was significantly higher in the GM/IFN-alpha APCs, whereas CD1a expression was significantly lower.
  • In mixed lymphocyte reactions (MLR), GM/IFN-alpha APCs stimulated the proliferation of allogeneic T cells significantly better than GM/IL-4 APCs.
  • Finally, we assessed the ability of GM/IFN-alpha APCs to induce a leukaemia-specific cytotoxic T-cell response.
  • [MeSH-major] Antigen-Presenting Cells / immunology. Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use. Interferon-alpha / therapeutic use. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology. Lymphocyte Activation. T-Lymphocytes, Cytotoxic / immunology
  • [MeSH-minor] Cell Differentiation. Cells, Cultured. Cytotoxicity Tests, Immunologic. Enzyme-Linked Immunosorbent Assay. Humans. In Situ Hybridization, Fluorescence. Interleukin-18 / analysis. Interleukin-4 / therapeutic use

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  • (PMID = 11122108.001).
  • [ISSN] 0007-1048
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] ENGLAND
  • [Chemical-registry-number] 0 / Interferon-alpha; 0 / Interleukin-18; 207137-56-2 / Interleukin-4; 83869-56-1 / Granulocyte-Macrophage Colony-Stimulating Factor
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12. Schmidli H, Peng B, Riviere GJ, Capdeville R, Hensley M, Gathmann I, Bolton AE, Racine-Poon A, IRIS Study Group: Population pharmacokinetics of imatinib mesylate in patients with chronic-phase chronic myeloid leukaemia: results of a phase III study. Br J Clin Pharmacol; 2005 Jul;60(1):35-44
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  • [Title] Population pharmacokinetics of imatinib mesylate in patients with chronic-phase chronic myeloid leukaemia: results of a phase III study.
  • AIMS: This study was designed to investigate the biochemical and physiological covariates or comedications that affect the pharmacokinetics of imatinib mesylate in patients with chronic-phase chronic myeloid leukaemia (CP CML).
  • METHODS: Pharmacokinetic data were analyzed in 371 patients receiving 400 mg imatinib once daily during a phase III trial of imatinib vs interferon-alfa plus cytarabine for the treatment of newly diagnosed CP CML.
  • Covariates included age, weight, sex, ethnicity, haemoglobin (Hb) concentration, white blood cell (WBC) count, liver function, and creatinine concentration.
  • Blood samples for imatinib analysis were taken on treatment days 1 and 29.
  • Nonlinear mixed effects modelling was used for the population pharmacokinetic analysis.
  • RESULTS: Population mean estimates (95% confidence interval) at day 1 for apparent clearance (CL) and apparent volume of distribution (V) of imatinib were 14 (13-15) l h(-1) and 252 (237-267) l, respectively.
  • Modelling suggested that CL decreased by 4 (3-5) l h(-1) from day 1 to day 29, whereas V remained unchanged.
  • Doubling body weight or Hb or halving the WBC count was associated with a 12%, 86% and 8% increase in CL, respectively, and a 32%, 60% and 5% increase in V, respectively.
  • CONCLUSIONS: Population covariates and coadministered drugs minimally affected imatinib pharmacokinetics in newly diagnosed CP CML patients.
  • [MeSH-major] Antineoplastic Agents / pharmacokinetics. Leukemia, Myeloid, Chronic-Phase / drug therapy. Piperazines / pharmacokinetics. Pyrimidines / pharmacokinetics
  • [MeSH-minor] Adolescent. Adult. Aged. Benzamides. Female. Humans. Imatinib Mesylate. Male. Middle Aged

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  • (PMID = 15963092.001).
  • [ISSN] 0306-5251
  • [Journal-full-title] British journal of clinical pharmacology
  • [ISO-abbreviation] Br J Clin Pharmacol
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase III; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate
  • [Other-IDs] NLM/ PMC1884912
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13. Gupta S, Jen J, Kolz K, Cutler D: Dose selection and population pharmacokinetics of PEG-Intron in patients with chronic myelogenous leukaemia. Br J Clin Pharmacol; 2007 Mar;63(3):292-9
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  • [Title] Dose selection and population pharmacokinetics of PEG-Intron in patients with chronic myelogenous leukaemia.
  • AIMS: To assess the dose selection using population pharmacokinetics of Pegylated Intron-alpha2b (PEG-Intron) in patients with chronic myelogenous leukaemia (CML).
  • METHODS: PEG-Intron 3-6 microg kg(-1) was administered subcutaneously once a week and blood samples were collected up to 48 weeks of treatment.
  • A total of 624 samples collected from 137 patients were included in the analysis.
  • Nonlinear mixed-effects modelling was used to analyse the sparsely sampled concentration data from a clinical efficacy trial.
  • Covariates in the analysis included weight, sex, age, race, serum creatinine and estimated creatinine clearance (CLcr).
  • The clearance at treatment week 4 was 42.3 l day(-1) (patients with CLcr 120 ml min(-1)) with interpatient variability 30%.
  • At treatment week 48, the clearance value was reduced to 69% of its week 4 value.
  • CLcr, a composite variable calculated from body weight, sex, age and serum creatinine, had a small but statistically significant influence on the clearance of PEG-Intron.
  • CONCLUSION: The dose of PEG-Intron 6.0 microg kg(-1) week(-1) appeared appropriate in the treatment of patients with CML.
  • [MeSH-major] Antiviral Agents / therapeutic use. Interferon-alpha / therapeutic use. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • [MeSH-minor] Adult. Aged. Female. Humans. Male. Middle Aged. Models, Biological. Polyethylene Glycols. Recombinant Proteins

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  • (PMID = 16939523.001).
  • [ISSN] 0306-5251
  • [Journal-full-title] British journal of clinical pharmacology
  • [ISO-abbreviation] Br J Clin Pharmacol
  • [Language] eng
  • [Publication-type] Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antiviral Agents; 0 / Interferon-alpha; 0 / Recombinant Proteins; 0 / peginterferon alfa-2b; 30IQX730WE / Polyethylene Glycols; 99210-65-8 / interferon alfa-2b
  • [Other-IDs] NLM/ PMC2000735
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14. Main C, Pitt M, Moxham T, Stein K: The clinical effectiveness and cost-effectiveness of rituximab for the first-line treatment of chronic lymphocytic leukaemia: an evidence review of the submission from Roche. Health Technol Assess; 2010 Oct;14(Suppl. 2):27-32
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] The clinical effectiveness and cost-effectiveness of rituximab for the first-line treatment of chronic lymphocytic leukaemia: an evidence review of the submission from Roche.
  • This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of rituximab for the first-line treatment of chronic lymphocytic leukaemia (CLL) based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process.
  • The submission's evidence came from a single, unpublished, well-conducted randomised controlled trial (RCT) comparing rituximab in combination with fludarabine and cyclophosphamide (R-FC) with fludarabine and cyclophosphamide (FC) alone for the first-line treatment of CLL.
  • However, the initial significant treatment benefit for R-FC compared with FC for overall survival was not maintained at a slightly longer follow-up time [median 25.4 months; adjusted HR 0.72 (95% CI 0.48 to 1.09)].
  • Response rates, numbers of patients with event-free survival and duration of response all favoured treatment with R-FC.
  • Additional evidence from a mixed-treatment comparison model indicated R-FC to be significantly superior to chlorambucil alone for both PFS and overall and complete response rates.
  • Dose modifications were also more frequent in this arm, but this did not lead to differences in treatment discontinuation.
  • The model used a cycle length of 1 month and a lifetime time horizon.
  • The base-case analysis produced an incremental cost-effectiveness ratio (ICER) of 13,189 pounds per quality-adjusted life-year (QALY) for R-FC versus FC, and 6422 pounds per QALY for the comparison of R-FC versus chlorambucil, suggesting that R-FC is cost-effective at normal willingness-to-pay thresholds.
  • One-way sensitivity analyses produced a range of ICERs from 10,249 pounds to 22,661 pounds per QALY for R-FC versus FC, and 5612 pounds and 6921 pounds per QALY for R-FC versus chlorambucil.
  • Probabilistic sensitivity analysis results matched the deterministic results very closely.
  • However, the sensitivity analysis did not fully investigate the uncertainty associated with differential values across arms or with the structural assumptions of the model, and utility values were not drawn from an empirical study.
  • The NICE guidance issued as a result of the STA states that: Rituximab in combination with fludarabine and cyclophosphamide (R-FC) is recommended as an option for the first-line treatment of chronic lymphocytic leukaemia in people for whom fludarabine in combination with cyclophosphamide (FC) is considered appropriate.
  • Rituximab in combination with chemotherapy agents other than fludarabine and cyclophosphamide is not recommended for the first-line treatment of chronic lymphocytic leukaemia.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
  • [MeSH-minor] Antibodies, Monoclonal, Murine-Derived / administration & dosage. Antibodies, Monoclonal, Murine-Derived / economics. Cost-Benefit Analysis. Cyclophosphamide / administration & dosage. Cyclophosphamide / economics. Great Britain. Humans. Randomized Controlled Trials as Topic. Rituximab. Vidarabine / administration & dosage. Vidarabine / analogs & derivatives. Vidarabine / economics

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  • (PMID = 21047488.001).
  • [ISSN] 2046-4924
  • [Journal-full-title] Health technology assessment (Winchester, England)
  • [ISO-abbreviation] Health Technol Assess
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal, Murine-Derived; 4F4X42SYQ6 / Rituximab; 8N3DW7272P / Cyclophosphamide; FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine
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15. Eiden C, Peyrière H, Tichit R, Cociglio M, Amedro P, Blayac JP, Margueritte G, Hillaire-Buys D: Inherited long QT syndrome revealed by antifungals drug-drug interaction. J Clin Pharm Ther; 2007 Jun;32(3):321-4
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  • [Title] Inherited long QT syndrome revealed by antifungals drug-drug interaction.
  • A 14-year-old Tahitian girl with acute myeloid leukaemia and a suspected mucormucosis infection was treated with intravenous voriconazole and caspofungin.
  • During the switch, the patient presented with QT interval prolongation with 'torsades de pointes' and reversible cardiac arrest.
  • The association of antifungal agents with pro-arrhythmogenic drugs and other risk factors led to torsades de pointes and the revealing of inherited QT syndrome.
  • [MeSH-major] Antifungal Agents / adverse effects. Long QT Syndrome / chemically induced. Torsades de Pointes / chemically induced
  • [MeSH-minor] Acute Disease. Adolescent. Aryl Hydrocarbon Hydroxylases / genetics. Cytochrome P-450 CYP2C19. Cytochrome P-450 CYP2C9. Female. Genotype. Humans. Injections, Intravenous. Leukemia, Myeloid / complications. Mixed Function Oxygenases / genetics. Mucormycosis / complications. Mucormycosis / drug therapy. Pyrimidines / administration & dosage. Pyrimidines / adverse effects. Pyrimidines / therapeutic use. Triazoles / administration & dosage. Triazoles / adverse effects. Triazoles / therapeutic use. Voriconazole

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  • (PMID = 17489884.001).
  • [ISSN] 0269-4727
  • [Journal-full-title] Journal of clinical pharmacy and therapeutics
  • [ISO-abbreviation] J Clin Pharm Ther
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antifungal Agents; 0 / Pyrimidines; 0 / Triazoles; 6TK1G07BHZ / posaconazole; EC 1.- / Mixed Function Oxygenases; EC 1.14.13.- / CYP2C9 protein, human; EC 1.14.13.- / Cytochrome P-450 CYP2C19; EC 1.14.13.- / Cytochrome P-450 CYP2C9; EC 1.14.14.1 / Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1 / CYP2C19 protein, human; JFU09I87TR / Voriconazole
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16. Rezk H, el-Shazly AM, Soliman M, el-Nemr HI, Nagaty IM, Fouad MA: Coccidiosis among immuno-competent and -compromised adults. J Egypt Soc Parasitol; 2001 Dec;31(3):823-34

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • There was significant increase in coccidia positive cases among Hodgkin lymphoma receiving chemotherapy as compared to control group (p < 0.05).
  • The increase was highly significant in the group of acute lymphocytic leukaemia receiving chemotherapy as compared to control group (P < 0.01).
  • The total percent of cases with single type of coccidia were 12.2% compared to multiple coccidial infections (4.3%).
  • The most commonly associated parasite was Cryptosporidium.
  • The total cryptosporidial infections (single and mixed with other coccidia) were 12.1% of the total studied cases.
  • Microsporidial infections (single and mixed with other coccidia), being the least detected among the four intestinal spores forming coccidia, were 2.4% in the immunocompromised groups.
  • The total cyclosporal infections (single and mixed with other coccidia) were 6.3% of the total studied cases.
  • In the immunocompromised groups, the prevalence was (8.3%) where in immunocompetent group, was 2.8%.
  • Single cyclospora was 3.0% while mixed Cyclospora represented 3.3% of all studied cases.
  • The Isospora infections (single and mixed) were 3.8% of total patients.
  • The prevalence among immunocompromised group was 5.2% and in immunocompetent patients was 2.8%.
  • [MeSH-minor] Adult. Aged. Animals. Antineoplastic Agents / adverse effects. Egypt / epidemiology. Female. Hodgkin Disease / complications. Hodgkin Disease / drug therapy. Hodgkin Disease / immunology. Humans. Male. Middle Aged. Precursor Cell Lymphoblastic Leukemia-Lymphoma / complications. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology

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  • (PMID = 11775108.001).
  • [ISSN] 1110-0583
  • [Journal-full-title] Journal of the Egyptian Society of Parasitology
  • [ISO-abbreviation] J Egypt Soc Parasitol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Egypt
  • [Chemical-registry-number] 0 / Antineoplastic Agents
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17. Ng A, Ravetto PF, Taylor GM, Wynn RF, Eden OB: Coexistence of treatment-related MLL cleavage and rearrangement in a child with haemophagocytic lymphohistiocytosis. Br J Cancer; 2004 Dec 13;91(12):1990-2
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  • [Title] Coexistence of treatment-related MLL cleavage and rearrangement in a child with haemophagocytic lymphohistiocytosis.
  • Treatment-related acute myeloid leukaemia (t-AML) is a serious complication of topoisomerase 2 inhibitor therapy and is characterised by the presence of mixed lineage leukaemia (MLL) rearrangement.
  • By molecular tracking, we were able to show that MLL cleavage preceded gene rearrangement by 3 months and before the clinical diagnosis of t-AML in a patient with haemophagocytic lymphohistiocytosis.
  • This is the first report on the sequential detection of the two biomarkers in treatment-related leukaemogenesis.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / adverse effects. DNA-Binding Proteins / genetics. Histiocytosis, Non-Langerhans-Cell / drug therapy. Leukemia, Myelomonocytic, Acute / etiology. Neoplasms, Second Primary / genetics. Nucleic Acid Synthesis Inhibitors / adverse effects. Proto-Oncogenes / genetics. Transcription Factors / genetics
  • [MeSH-minor] Blotting, Southern. Dexamethasone / administration & dosage. Epstein-Barr Virus Infections / complications. Etoposide / adverse effects. Gene Rearrangement. Histone-Lysine N-Methyltransferase. Humans. Infant. Male. Methotrexate / administration & dosage. Myeloid-Lymphoid Leukemia Protein. Polymerase Chain Reaction. Time Factors. Topoisomerase II Inhibitors

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  • (PMID = 15570305.001).
  • [ISSN] 0007-0920
  • [Journal-full-title] British journal of cancer
  • [ISO-abbreviation] Br. J. Cancer
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / DNA-Binding Proteins; 0 / MLL protein, human; 0 / Nucleic Acid Synthesis Inhibitors; 0 / Topoisomerase II Inhibitors; 0 / Transcription Factors; 149025-06-9 / Myeloid-Lymphoid Leukemia Protein; 6PLQ3CP4P3 / Etoposide; 7S5I7G3JQL / Dexamethasone; EC 2.1.1.43 / Histone-Lysine N-Methyltransferase; YL5FZ2Y5U1 / Methotrexate
  • [Other-IDs] NLM/ PMC2409780
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18. Olavarria E, Ottmann OG, Deininger M, Clark RE, Bandini G, Byrne J, Lipton J, Vitek A, Michallet M, Siegert W, Ullmann A, Wassmann B, Niederwieser D, Fischer T, Chronic Leukaemia Working Party of the European Group of Bone and Marrow Transplantation (EBMT): Response to imatinib in patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia. Leukemia; 2003 Sep;17(9):1707-12
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Response to imatinib in patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia.
  • We studied 128 patients with chronic myeloid leukemia (CML) relapsing after allogeneic stem cell transplantation (SCT).
  • Disease at the time of treatment with Imatinib was in chronic phase (CP) in 51 patients, accelerated phase (AP) in 31 and blastic crisis (BC) in 46.
  • Of the 51 patients in CP, 14 were in cytogenetic and two in molecular relapses.
  • The median interval between relapse and Imatinib therapy was 5 months (0-65).
  • A total of 50 patients had failed treatment with donor lymphocyte infusions prior to Imatinib.
  • Complete molecular responses were obtained in 25 patients (26%), of whom 21 were in CP or AP.
  • With a median follow-up of 9 months, the estimated 2-year survival for CP, AP and BC patients was 100, 86 and 12%, respectively.
  • Out of 79 evaluable patients, 45 (57%) achieved full donor and 11 (14%) mixed chimerism after Imatinib.
  • We conclude that Imatinib has significant activity against CML in relapse after allogeneic SCT.
  • Durable cytogenetic and molecular remissions are obtainable in patients in CP.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Hematopoietic Stem Cell Transplantation / adverse effects. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Neoplasm Recurrence, Local / drug therapy. Piperazines / therapeutic use. Pyrimidines / therapeutic use
  • [MeSH-minor] Adult. Aged. Benzamides. Female. Graft vs Leukemia Effect. Humans. Imatinib Mesylate. Male. Middle Aged. Retrospective Studies. Salvage Therapy. Survival Rate. Transplantation, Homologous. Treatment Outcome


19. Schimmer AD, O'Brien S, Kantarjian H, Brandwein J, Cheson BD, Minden MD, Yee K, Ravandi F, Giles F, Schuh A, Gupta V, Andreeff M, Koller C, Chang H, Kamel-Reid S, Berger M, Viallet J, Borthakur G: A phase I study of the pan bcl-2 family inhibitor obatoclax mesylate in patients with advanced hematologic malignancies. Clin Cancer Res; 2008 Dec 15;14(24):8295-301
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  • PURPOSE: The outcome of patients with refractory leukemia and myelodysplasia is poor, and new therapies are needed.
  • The antiapoptotic proteins of the Bcl-2 family are overexpressed in these malignancies and are potential therapeutic targets.
  • Therefore, we conducted a phase I clinical trial of the small-molecule pan-Bcl-2 inhibitor, obatoclax mesylate, in patients with refractory leukemia and myelodysplasia to assess its safety and define its optimal dose.
  • EXPERIMENTAL DESIGN: Forty-four patients with refractory leukemia or myelodysplasia were treated with obatoclax mesylate by continuous intravenous infusion at increasing doses and frequencies.
  • RESULTS: A total of 306 infusions of obatoclax mesylate were administered with a median of 5 infusions per patient.
  • The study drug was well tolerated up to the highest dose planned without dose-limiting toxicity.
  • Grade 1/2 central nervous system symptoms were the most common adverse events attributable to the study drug.
  • One patient with acute myeloid leukemia with mixed lineage leukemia t(9;11) rearrangement achieved a complete remission, which lasted 8 months.
  • CONCLUSIONS: Obatoclax mesylate is well tolerated and these results support its further investigation in patients with leukemia and myelodysplasia.
  • [MeSH-major] Leukemia / drug therapy. Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors. Pyrroles / therapeutic use
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Electrocardiography / drug effects. Female. Humans. Male. Middle Aged

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  • (PMID = 19088047.001).
  • [ISSN] 1078-0432
  • [Journal-full-title] Clinical cancer research : an official journal of the American Association for Cancer Research
  • [ISO-abbreviation] Clin. Cancer Res.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / P30 CA016672
  • [Publication-type] Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Proto-Oncogene Proteins c-bcl-2; 0 / Pyrroles; 0 / obatoclax
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20. Perkhofer S, Lass-Flörl C, Hell M, Russ G, Krause R, Hönigl M, Geltner C, Auberger J, Gastl G, Mitterbauer M, Willinger B, Knöbl P, Resch G, Waldner R, Makrai A, Hartmann G, Girschikofsky M, Greil R: The Nationwide Austrian Aspergillus Registry: a prospective data collection on epidemiology, therapy and outcome of invasive mould infections in immunocompromised and/or immunosuppressed patients. Int J Antimicrob Agents; 2010 Dec;36(6):531-6
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] The Nationwide Austrian Aspergillus Registry: a prospective data collection on epidemiology, therapy and outcome of invasive mould infections in immunocompromised and/or immunosuppressed patients.
  • A prospective, observational, multicentre study was performed to assess the incidence, diagnosis, epidemiology and outcome of invasive mould infections (IMIs) reported to the Nationwide Austrian Aspergillus Registry.
  • In total, 186 cases were recorded, corresponding to an annual incidence of 42 cases/1000 patients at risk or 2.36 cases/100000 inhabitants.
  • Patients with acute myelogenous leukaemia (34%) and lung transplant recipients (17%) are currently at highest risk for IMI, followed by a mixed population with impaired immunity (14%).
  • Multivariate analysis showed that outcome and survival did not correlate with the status of fungal disease, breakthrough infection, fungal species or age (P>0.05).
  • [MeSH-major] Antifungal Agents / therapeutic use. Aspergillosis / drug therapy. Aspergillosis / epidemiology
  • [MeSH-minor] Adolescent. Adult. Aged. Aged, 80 and over. Austria / epidemiology. Female. Humans. Immunocompromised Host. Incidence. Male. Middle Aged. Prospective Studies. Survival Analysis. Treatment Outcome. Young Adult

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  • [Copyright] Copyright © 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
  • (PMID = 20947312.001).
  • [ISSN] 1872-7913
  • [Journal-full-title] International journal of antimicrobial agents
  • [ISO-abbreviation] Int. J. Antimicrob. Agents
  • [Language] eng
  • [Publication-type] Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Antifungal Agents
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