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Randomized Controlled Trial
. 2007 Jan 1;109(1):46-51.
doi: 10.1182/blood-2006-01-023101. Epub 2006 Sep 19.

Therapy-related myelodysplasia and acute myeloid leukemia after Ewing sarcoma and primitive neuroectodermal tumor of bone: A report from the Children's Oncology Group

Smita Bhatia  1 , Mark D Krailo, Zhengjia Chen, Laura Burden, Frederic B Askin, Paul S Dickman, Holcombe E Grier, Michael P Link, Paul A Meyers, Elizabeth J Perlman, Aaron R Rausen, Leslie L Robison, Teresa J Vietti, James S Miser
Affiliations
Randomized Controlled Trial

Therapy-related myelodysplasia and acute myeloid leukemia after Ewing sarcoma and primitive neuroectodermal tumor of bone: A report from the Children's Oncology Group

Smita Bhatia et al. Blood. .

Abstract

This study describes the magnitude of risk of therapy-related myelodysplasia and acute myeloid leukemia (t-MDS/AML) in 578 individuals diagnosed with Ewing sarcoma and enrolled on Children's Oncology Group therapeutic protocol, INT-0091. Between 1988 and 1992, patients with or without metastatic disease were randomized to receive doxorubicin, vincristine, cyclophosphamide, and dactinomycin (regimen A) or these 4 drugs alternating with etoposide and ifosfamide (regimen B). Between 1992 and 1994, patients with metastatic disease were nonrandomly assigned to receive high-intensity therapy (regimen C: regimen B therapy with higher doses of doxorubicin, cyclophosphamide, and ifosfamide). Median age at diagnosis of Ewing sarcoma was 12 years, and median length of follow-up, 8 years. Eleven patients developed t-MDS/AML, resulting in a cumulative incidence of 2% at 5 years. While patients treated on regimens A and B were at a low risk for development of t-MDS/AML (cumulative incidence: 0.4% and 0.9% at 5 years, respectively), patients treated on regimen C were at a 16-fold increased risk of developing t-MDS/AML (cumulative incidence: 11% at 5 years), when compared with those treated on regimen A. Increasing exposure to ifosfamide from 90 to 140 g/m2, cyclophosphamide from 9.6 to 17.6 g/m2, and doxorubicin from 375 to 450 mg/m2 increased the risk of t-MDS/AML significantly.

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Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

Figure 1
Figure 1
Graphic representation of the treatment schema. VAdCA denotes vincristine, doxorubicin, cyclophosphamide, and dactinomycin. I/E denotes ifosfamide and etoposide. VAdCA* and I/E* denote high-intensity vincristine, doxorubicin, cyclophosphamide, dactinomycin, ifosfamide, and etoposide as described in “Study design.”
Figure 2
Figure 2
Cumulative incidence of t-MDS/AML in patients treated on COG therapeutic trial INT-0091.
Figure 3
Figure 3
Cumulative incidence of t-MDS/AML in patients treated on COG therapeutic trial INT-0091, by treatment regimen.
See this image and copyright information in PMC

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