Document Detail

Evaluation of antileukaemic effects of rapamycin in patients with imatinib-resistant chronic myeloid leukaemia.
MedLine Citation:
PMID:  18173550     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Recent data suggest that the mammalian target of rapamycin (mTOR) is involved in the regulation of growth of neoplastic cells in chronic myeloid leukaemia (CML). PATIENTS AND METHODS: We treated six patients with imatinib-resistant CML in haematological relapse (leukocytes > 20,000 microL(-1)) with rapamycin at 2 mg per os daily for 14 consecutive days, with dose-adjustment allowed to reach a target rapamycin serum concentration of 10-20 pg mL(-1). RESULTS: A major leukocyte response with decrease to less than 10,000 microL(-1) was obtained in two patients, and a minor transient response was seen in two other patients. In responding patients, we also observed a decrease in vascular endothelial growth factor (VEGF) mRNA levels in circulating leukaemic cells. Side effects during rapamycin treatment were mild in most patients. In one patient, pneumonia developed. Rapamycin was also found to counteract growth of CML cells in vitro as determined by (3)H-thymidine incorporation. Moreover, rapamycin inhibited the growth of Ba/F3 cells exhibiting various imatinib-resistant mutants of BCR/ABL, including the T315I variant that exhibits resistance against most currently available BCR/ABL kinase inhibitors. CONCLUSIONS: Rapamycin shows antileukaemic effects in imatinib-resistant CML in vitro and in vivo. Larger trials with rapamycin or rapamycin-derivatives in combination with other targeted drugs are warranted to further determine clinical efficacy in CML.
C Sillaber; M Mayerhofer; A Böhm; A Vales; A Gruze; K J Aichberger; H Esterbauer; M Pfeilstöcker; W R Sperr; W F Pickl; O A Haas; P Valent
Publication Detail:
Type:  Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of clinical investigation     Volume:  38     ISSN:  1365-2362     ISO Abbreviation:  Eur. J. Clin. Invest.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2008-01-04     Completed Date:  2008-05-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0245331     Medline TA:  Eur J Clin Invest     Country:  England    
Other Details:
Languages:  eng     Pagination:  43-52     Citation Subset:  IM    
Department of Internal Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Vienna, Austria.
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MeSH Terms
Antibiotics, Antineoplastic / therapeutic use*
Antineoplastic Agents / therapeutic use*
Drug Evaluation
Drug Resistance, Neoplasm
Leukemia, Myeloid, Chronic-Phase / drug therapy*
Middle Aged
Pilot Projects
Piperazines / therapeutic use*
Pyrimidines / therapeutic use*
RNA, Messenger / metabolism
RNA, Neoplasm / metabolism
Sirolimus / therapeutic use*
Treatment Outcome
Vascular Endothelial Growth Factor A / metabolism
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Antineoplastic Agents; 0/Piperazines; 0/Pyrimidines; 0/RNA, Messenger; 0/RNA, Neoplasm; 0/VEGFA protein, human; 0/Vascular Endothelial Growth Factor A; 152459-95-5/imatinib; 53123-88-9/Sirolimus

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