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Myelodysplastic Syndrome and Acute Myeloid Leukemia Postcytotoxic Therapy (MDS-pCT and AML-pCT)
Source: Late Effects of Treatment for Childhood Cancer (PDQ®)–Health Professional Version, National Cancer Institute.
Source updated: April 14, 2025 · Captured 2026-09-09.
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Subsequent primary leukemias have been reported in survivors of Hodgkin lymphoma, leukemia, sarcoma, CNS tumors, non-Hodgkin lymphoma, neuroblastoma, and Wilms tumor. In a cohort of nearly 70,000 5-year childhood cancer survivors, survivors had a fourfold increased risk (SIR, 3.7) of developing a leukemia, with an absolute excess risk of 7.5. Specifically, a sixfold relative risk of developing a myeloid leukemia (SIR, 5.8) was reported.[15]
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The risk remained significantly elevated beyond 20 years from the first primary malignancy (SIR, 2.4).
Hodgkin lymphoma survivors had the greatest excess risk of developing a subsequent leukemia (SIR, 7.9) and specifically a myeloid leukemia (SIR, 12.1), with the largest excess risk seen before 20 years of follow-up.
A pooled analysis examined all published studies with detailed treatment data for children with cancer diagnosed between 1930 and 2000. Treatment data included estimated radiation doses to the active bone marrow and doses of specific chemotherapy agents. In this report, 147 cases of second primary leukemia (69% of cases were AML) were matched to 522 controls.[16]
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After controlling for other therapies, topoisomerase II inhibitor therapy was associated with an increased risk of second AML (no radiation and >2,500 mg/m2 vs. none: OR, 14.3; 95% CI, 2.7–75.1).
Radiation dose to the active bone marrow was also associated with an increased risk of second AML among patients who did not receive chemotherapy (>0–12 Gy: OR, 4.9; 95% CI, 0.95–25.6) but not among those who received chemotherapy.
Second primary leukemias were most likely to occur in the first decade after cancer treatment.[17]
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A short latency (<10 years from primary cancer diagnosis). The risk of MDS-pCT or AML-pCT plateaus after 10 to 15 years. Although the risk of subsequent leukemia remains significantly elevated beyond 15 years from primary diagnosis (SIR, 3.5; 95% CI, 1.9–6.0), these events are relatively rare, with an absolute excess risk of 0.02 cases per 1,000 person-years.[19]
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An association with alkylating agents and/or topoisomerase II inhibitors.
Based on the updated definitions from the World Health Organization, MDS-pCT and AML-pCT are clonal disorders, which arise in patients previously exposed to cytotoxic therapy, either chemotherapy or large-field radiation therapy, for an unrelated neoplasm.[20] The following two types of MDS-pCT and AML-pCT are the most frequently observed among survivors:
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Alkylating agent–related type: Alkylating agents associated with MDS-pCT and AML-pCT include cyclophosphamide, ifosfamide, mechlorethamine, melphalan, busulfan, nitrosoureas, chlorambucil, and dacarbazine.[21] The risk of alkylating agent–related MDS or AML is dose dependent, with a latency of 3 to 5 years after exposure; it is associated with abnormalities involving chromosomes 5 (-5/del(5q)) and 7 (-7/del(7q)).[21]
Topoisomerase II inhibitor–related type: Topoisomerase II inhibitor agents include etoposide, teniposide, and anthracycline-related drugs.Most of the translocations observed in patients exposed to topoisomerase II inhibitors disrupt a breakpoint cluster region between exons 5 and 11 of the band 11q23 and fuse KMT2A with a partner gene.[21] Topoisomerase II inhibitor–related AML presents as overt leukemia after a latency of 6 months to 3 years and is associated with balanced translocations involving chromosome bands 11q23 or 21q22.[22]
For more information, see the Therapy-Related AML and Therapy-Related Myelodysplastic Neoplasms section in Childhood Acute Myeloid Leukemia Treatment.
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Preserved source evidence · Not medical advice