Evolving risk of therapy-related acute myeloid leukemia following cancer chemotherapy among adults in the United States, 1975-2008

Lindsay M. Morton, Graça M. Dores, Margaret A. Tucker, Clara J. Kim, Kenan Onel, Ethel S. Gilbert, Joseph F. Fraumeni Jr. and Rochelle E. Curtis

Key points

  • Coincident with major changes in cancer treatments, the occurrence of tAML has changed significantly over time.

  • tAML risks should be weighed against the benefits of chemotherapy.


Therapy-related acute myeloid leukemia (tAML) is a rare but highly fatal complication of cytotoxic chemotherapy. Despite major changes in cancer treatment, data describing tAML risks over time are sparse. Among 426,068 adults initially treated with chemotherapy for first primary malignancy (nine US population-based cancer registries, 1975-2008), we identified 801 tAML cases, 4.70-times more than expected in the general population (P<0.001). Over time, tAML risks increased following chemotherapy for non-Hodgkin lymphoma (n=158, Poisson regression Ptrend<0.001), declined for ovarian cancer (n=72, Ptrend<0.001), myeloma (n=62, Ptrend=0.02), and possibly lung cancer (n=65, Ptrend=0.18), and were significantly heterogeneous for breast cancer (n=223, Phomogeneity=0.005) and Hodgkin lymphoma (n=58, Phomogeneity=0.007). tAML risks varied significantly by age at first cancer and latency and were nonsignificantly heightened with radiotherapy for lung, breast, and ovarian cancers. We identified newly emerging elevated tAML risks for patients treated with chemotherapy since 2000 for esophageal, cervical, prostate and possibly anal cancers; and since the 1990s for bone/joint and endometrial cancers. Using long-term, population-based data, we observed significant variation in tAML risk over time, consistent with changing treatment practices and differential leukemogenicity of specific therapies. tAML risks should be weighed against benefits of chemotherapy, particularly for new agents and new indications for standard agents.

  • Submitted August 6, 2012.
  • Accepted January 23, 2013.