Document Detail

Therapy-related acute myeloid leukemia following treatment with epipodophyllotoxins: estimating the risks.
MedLine Citation:
PMID:  8202047     Owner:  NLM     Status:  MEDLINE    
In the past decade, therapy-related acute myeloid leukemia (t-AML) following treatment with regimens that include inhibitors of topoisomerase-II (TOPO-II) has been reported with increasing frequency. These cases of t-AML generally have a shorter latency period than t-AML following alkylator therapy, are associated with chromosomal translocations (especially involving chromosome band 11q23), and usually present as M4 or M5 FAB subtype. Although the epipodophyllotoxins (etoposide and teniposide) have been most often implicated, similar cases of t-AML occur following therapy with other classes of Topo-II inhibitors (e.g., anthracyclines). There is wide variation in published studies in the estimates of risk of t-AML following epipodophyllotoxin therapy. These varying estimates may reflect a number of factors, including: small sample size leading to large confidence intervals around risk estimates; varying susceptibility of different patient populations; varying schedules of epipodophyllotoxin administration; different cumulative doses of epipodophyllotoxins; and administration of epopodophyllotoxins with additional agents that may alter the leukemogenic effect of the epipodophyllotoxins. Available data suggest that children with acute lymphocytic leukemia (ALL) treated with high cumulative doses of epipodophyllotoxins using either weekly or twice-weekly schedules of administration have a relatively high risk of developing t-AML (5-12% cumulative risk). On the other hand, germ cell patients treated with relatively low cumulative doses of etoposide (usually 1,500-2,500 mg/m2) appear to have a low risk for developing t-AML. There is inadequate experience at this time with higher cumulative doses of etoposide (e.g., 4,000-5,000 mg/m2 as used for pediatric solid tumors) given on a daily x 5 schedule to allow estimates of risk to be developed for this schedule and cumulative dose. The Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) has developed a monitoring plan designed to obtain reliable estimates of the risk of t-AML following epipodophyllotoxin treatment. Twelve Cooperative Group clinical trials that use epipodophyllotoxins at either low (< 1,500 mg/m2), moderate (1,500-3,999 mg/m2), or higher cumulative doses (> 4,000 mg/m2) are being prospectively monitored for cases of t-AML occurring among patients entered onto the trials.
M A Smith; L Rubinstein; R S Ungerleider
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Medical and pediatric oncology     Volume:  23     ISSN:  0098-1532     ISO Abbreviation:  Med. Pediatr. Oncol.     Publication Date:  1994  
Date Detail:
Created Date:  1994-07-06     Completed Date:  1994-07-06     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7506654     Medline TA:  Med Pediatr Oncol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  86-98     Citation Subset:  IM    
Cancer Therapy Evaluation Program, DCT, NCI, Bethesda, Maryland 20892.
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MeSH Terms
Alkylating Agents / adverse effects
Cell Cycle / drug effects
Chromosomes, Human, Pair 11
Clinical Trials as Topic
DNA Topoisomerases, Type II / antagonists & inhibitors*
Drug Administration Schedule
Leukemia, Monocytic, Acute / chemically induced
Leukemia, Myeloid, Acute / chemically induced*
Leukemia, Myelomonocytic, Acute / chemically induced
Lymphoma, Non-Hodgkin / drug therapy
Neoplasms, Second Primary / chemically induced*
Podophyllotoxin / adverse effects*
Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
Prospective Studies
Risk Factors
Translocation, Genetic
Reg. No./Substance:
0/Alkylating Agents; 518-28-5/Podophyllotoxin; EC Topoisomerases, Type II

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