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, 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

Research output: Contribution to journalArticle

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 followup, 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.

Original languageEnglish (US)
Pages (from-to)46-51
Number of pages6
JournalBlood
Volume109
Issue number1
DOIs
StatePublished - Jan 1 2007

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Primitive Neuroectodermal Tumors
Ewing's Sarcoma
Oncology
Acute Myeloid Leukemia
Ifosfamide
Tumors
Bone
Doxorubicin
Cyclophosphamide
Bone and Bones
Dactinomycin
Vincristine
Etoposide
Therapeutics
Incidence
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Hematology

Cite this

Therapy-related myelodysplasia and acute myeloid leukemia after Ewing sarcoma and primitive neuroectodermal tumor of bone : A report from the Children's Oncology Group. / Bhatia, Smita; Krailo, Mark D.; Chen, Zhengjia; Burden, Laura; Askin, Frederic B; Dickman, Paul S.; Grier, Holcombe E.; Link, Michael P.; Meyers, Paul A.; Perlman, Elizabeth J.; Rausen, Aaron R.; Robison, Leslie L.; Vietti, Teresa J.; Miser, James S.

In: Blood, Vol. 109, No. 1, 01.01.2007, p. 46-51.

Research output: Contribution to journalArticle

Bhatia, S, Krailo, MD, Chen, Z, Burden, L, Askin, FB, Dickman, PS, Grier, HE, Link, MP, Meyers, PA, Perlman, EJ, Rausen, AR, Robison, LL, Vietti, TJ & Miser, JS 2007, 'Therapy-related myelodysplasia and acute myeloid leukemia after Ewing sarcoma and primitive neuroectodermal tumor of bone: A report from the Children's Oncology Group', Blood, vol. 109, no. 1, pp. 46-51. https://doi.org/10.1182/blood-2006-01-023101
Bhatia, Smita ; Krailo, Mark D. ; Chen, Zhengjia ; Burden, Laura ; Askin, Frederic B ; Dickman, Paul S. ; Grier, Holcombe E. ; Link, Michael P. ; Meyers, Paul A. ; Perlman, Elizabeth J. ; Rausen, Aaron R. ; Robison, Leslie L. ; Vietti, Teresa J. ; Miser, James S. / Therapy-related myelodysplasia and acute myeloid leukemia after Ewing sarcoma and primitive neuroectodermal tumor of bone : A report from the Children's Oncology Group. In: Blood. 2007 ; Vol. 109, No. 1. pp. 46-51.
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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 followup, 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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T2 - A report from the Children's Oncology Group

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AU - Chen, Zhengjia

AU - Burden, Laura

AU - Askin, Frederic B

AU - Dickman, Paul S.

AU - Grier, Holcombe E.

AU - Link, Michael P.

AU - Meyers, Paul A.

AU - Perlman, Elizabeth J.

AU - Rausen, Aaron R.

AU - Robison, Leslie L.

AU - Vietti, Teresa J.

AU - Miser, James S.

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N2 - 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 followup, 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.

AB - 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 followup, 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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