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rdf:type |
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lifeskim:mentions |
umls-concept:C0023434,
umls-concept:C0024305,
umls-concept:C0030705,
umls-concept:C0049065,
umls-concept:C0332120,
umls-concept:C0445550,
umls-concept:C0599894,
umls-concept:C0854467,
umls-concept:C0920321,
umls-concept:C1512043,
umls-concept:C2613365,
umls-concept:C2613367
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pubmed:issue |
2
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pubmed:dateCreated |
2010-7-19
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pubmed:abstractText |
Targeting aberrant DNA hypermethylation in chronic lymphocytic leukaemia (CLL) and non-Hodgkin lymphoma (NHL) with decitabine may reverse epigenetic silencing in B-cell malignancies. Twenty patients were enrolled in two phase I trials to determine the minimum effective pharmacological dose of decitabine in patients with relapsed/refractory CLL (n = 16) and NHL (n = 4). Patients received 1-3 cycles of decitabine. Dose-limiting toxicity (DLT) was observed in 2 of 4 CLL and 2 of 2 NHL patients receiving decitabine at 15 mg/m(2) per d days 1-10, consisting of grade 3-4 thrombocytopenia and hyperbilirubinaemia. Six patients with CLL received decitabine at 10 mg/m(2) per d days 1-10 without DLT; however, re-expression of methylated genes or changes in global DNA methylation were not observed. Therefore, a 5-day decitabine schedule was examined. With 15 mg/m(2) per d decitabine days 1-5, DLT occurred in 2 of 6 CLL and 2 of 2 NHL patients, consisting of grade 3-4 neutropenia, thrombocytopenia, and febrile neutropenia. Eight patients had stable disease. In 17 patients, there were no significant changes in genome-wide methylation or in target gene re-expression. In conclusion, dose-limiting myelosuppression and infectious complications prevented dose escalation of decitabine to levels associated with changes in global methylation or gene re-expression in CLL and NHL.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20456354-10361133,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20456354-10561185,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20456354-10577857,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20456354-12708480,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20456354-14604977,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20456354-15059895,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20456354-15723065,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20456354-15809452,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20456354-15883410,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20456354-16333246,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20456354-16423993,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20456354-16523529,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20456354-16818276,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20456354-16882708,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20456354-17264127,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20456354-17540169,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20456354-17679729,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20456354-18078872,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20456354-18931345,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20456354-19470736,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20456354-8652811
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1365-2141
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pubmed:author |
pubmed-author:AndritsosLeslieL,
pubmed-author:BaiocchiRobertR,
pubmed-author:BensonDonald MDM,
pubmed-author:BlumKristie AKA,
pubmed-author:ByrdJohn CJC,
pubmed-author:ChanKenneth KKK,
pubmed-author:ChenPingP,
pubmed-author:DevineSteven MSM,
pubmed-author:FlynnJosephJ,
pubmed-author:GreverMichael RMR,
pubmed-author:JonesJeffreyJ,
pubmed-author:LiuZhongfaZ,
pubmed-author:LucasDavid MDM,
pubmed-author:MarcucciGuidoG,
pubmed-author:PlassChristophC,
pubmed-author:XieZhiliangZ
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pubmed:issnType |
Electronic
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pubmed:volume |
150
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
189-95
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pubmed:dateRevised |
2011-8-1
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pubmed:meshHeading |
pubmed-meshheading:20456354-Adult,
pubmed-meshheading:20456354-Aged,
pubmed-meshheading:20456354-Aged, 80 and over,
pubmed-meshheading:20456354-Antimetabolites, Antineoplastic,
pubmed-meshheading:20456354-Azacitidine,
pubmed-meshheading:20456354-DNA, Neoplasm,
pubmed-meshheading:20456354-DNA Methylation,
pubmed-meshheading:20456354-Dose-Response Relationship, Drug,
pubmed-meshheading:20456354-Drug Administration Schedule,
pubmed-meshheading:20456354-Female,
pubmed-meshheading:20456354-Humans,
pubmed-meshheading:20456354-Leukemia, Lymphocytic, Chronic, B-Cell,
pubmed-meshheading:20456354-Lymphoma, Non-Hodgkin,
pubmed-meshheading:20456354-Male,
pubmed-meshheading:20456354-Middle Aged,
pubmed-meshheading:20456354-Neutropenia,
pubmed-meshheading:20456354-Thrombocytopenia,
pubmed-meshheading:20456354-Treatment Outcome
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pubmed:year |
2010
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pubmed:articleTitle |
Phase I trial of low dose decitabine targeting DNA hypermethylation in patients with chronic lymphocytic leukaemia and non-Hodgkin lymphoma: dose-limiting myelosuppression without evidence of DNA hypomethylation.
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pubmed:affiliation |
Division of Hematology-Oncology, Department of Internal Medicine, The Arthur G. James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA. kristie.blum@osumc.edu
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Clinical Trial, Phase I,
Research Support, N.I.H., Extramural
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