Journal of Clinical Oncology, 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 26, No 15S (May 20 Supplement), 2008: 10005
© 2008 American Society of Clinical Oncology

This Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Shankar, S. M. Articles by Bhatia, S. Search for Related Content PubMed Articles by Shankar, S. M. Articles by Bhatia, S.

Abstract

Risk of therapy related myelodysplasia and acute myeloid leukemia (t-MDS/AML) in children exposed to alkylating agents, anthracyclines, platinum compounds and epipodophyllotoxins: a report from Children’s Oncology Group (COG)

GlaxoSmithKline, Collegeville, PA; Children’s Oncology Group, Arcadia, CA; City of Hope Cancer Center, Duarte, CA

10005

Background: Alkylating agents damage cellular DNA by producing DNA cross links, while epipodophyllotoxins inhibit topoisomerase II, and both are known to be potentially leukemogenic. Platinum compounds and anthracyclines exert their cytotoxic effects through similar mechanisms. The leukemogenic potential of platinum compounds and anthracyclines is less clear, and was explored in this study. Methods: A nested case-control study design was used. The cases were children diagnosed with t-MDS/AML between 1979 and 2000. For each case, multiple controls (1–4) were randomly selected from children treated on COG therapeutic protocols. Controls were matched with the cases for primary diagnosis, date of diagnosis and duration of follow-up. Cumulative exposures to alkylating agents, anthracyclines, platinum compounds, and epipodophyllotoxins were summarized. Conditional logistic regression was used for estimation of odds ratios. Results: A total of 71 cases and 219 controls were included in this study. Univariate analysis revealed associations between exposure to all four groups of agents at varying dose levels (above or below median dose): alkylating agents (< 8 gm/m2: OR=0.7, p=0.5; 8 gm/m²: OR=2.5, p=0.04); anthracyclines (<360 mg/m2:OR=3.1, p=0.2; 360 mg/m²: OR=4.2, p=0.09); platinum compounds: (<480mg/m²: OR=3.6, p=0.04; 480 mg/m²: OR=3.3, p=0.03); and epipodophyllotoxins (<3 gm/m²: OR=5.0, p=0.002, 3 gm/m²: OR=1.05, p=0.9). However, multivariate analysis, adjusted for exposures to all four agents (presence or absence of exposure), revealed therapy with platinum compounds (OR=5.9; p=0.004) and epipodophyllotoxins (OR=3.6; p=0.007) to be the only independent risk factors for development of t-MDS/AML. No clear dose response relationship could be established. Conclusions: Children treated with platinum compounds and epipodophyllotoxins for their primary cancer have a 3–6 fold higher risk of developing t-MDS/AML, after adjusting for known exposure to alkylating agents and anthracyclines. Further studies need to focus on the mechanism of t-MDS/AML associated with these exposures.

No significant financial relationships to disclose.

Abstract presentation from the 2008 ASCO Annual Meeting