High risk of leukemia after short-term dose-intensive chemotherapy in young patients with solid tumors Journal Article

Authors: Kushner, B. H.; Heller, G.; Cheung, N. V.; Wollner, N.; Kramer, K.; Bajorin, D.; Polyak, T.; Meyers, P. A.
Article Title: High risk of leukemia after short-term dose-intensive chemotherapy in young patients with solid tumors
Abstract: Purpose: To help fill the gap in knowledge about the risk of leukemia from repetitive high-dose use of alkylating agents and topoisomerase-II inhibitors in young patients with solid tumors. Methods: Poor-risk solid tumors were treated with four courses of cyclophosphamide (4,200 mg/m2)/doxorubicin (75 mg/m2), and three courses of ifosfamide (9,000 mg/m2)/etoposide (500 mg/m2). The cumulative incidence of treatment- related myelodysplasia/leukemia (t-AML) was calculated using the method of competing risks. The expected number of leukemic events was calculated by applying national incidence rates to person-years classified by age and sex. Results: Among 86 patients (median age, 17 years) monitored for 6 to 88 months (median, 24), five cases of t-AML were detected at 10 to 37 months (median, 17). The expected number of leukemic events in this cohort was .001. Clinical and cytogenetic findings implicated prior alkylator therapy in three cases and prior treatment with topoisomerase-II inhibitors in two. At 40 months, the cumulative incidence of t-AML was 8% (SE 7%). Conclusion: Repetitive high-dose use of alkylating agents given with topoisomerase-II inhibitors is strongly leukemogenic, even with modest cumulative doses of each drug. This finding is notable for the following reasons: (1) it undermines predictions that limited use of high-dose chemotherapy might be minimally leukemogenic, and (2) it contrasts strikingly with the previously reported low risk of t-AML following treatment of pediatric solid tumors with chemotherapy lacking the alkylator dose-intensity and prominence of etoposide that are hallmarks of current regimens.
Keywords: adolescent; adult; cancer chemotherapy; child; leukemia; major clinical study; doxorubicin; cancer risk; solid tumor; drug megadose; prospective studies; neoplasms; etoposide; antineoplastic combined chemotherapy protocols; drug administration schedule; risk factors; alkylating agent; cyclophosphamide; vincristine; dose-response relationship, drug; ifosfamide; infant; neoplasms, second primary; second cancer; dna topoisomerase inhibitor; myelodysplastic syndromes; humans; human; male; female; priority journal; article
Journal Title: Journal of Clinical Oncology
Volume: 16
Issue: 9
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 1998-09-01
Start Page: 3016
End Page: 3020
Language: English
PUBMED: 9738570
PROVIDER: scopus
DOI: 10.1200/JCO.1998.16.9.3016
Notes: Article -- Export Date: 12 December 2016 -- Source: Scopus
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MSK Authors
  1. Brian Kushner
    190 Kushner
  2. Dean Bajorin
    404 Bajorin
  3. Glenn Heller
    291 Heller
  4. Nai-Kong Cheung
    439 Cheung
  5. Kim Kramer
    168 Kramer
  6. Tatyana A Polyak
    10 Polyak
  7. Paul Meyers
    243 Meyers