title: Evolving risk of therapy-related acute myeloid leukemia following cancer chemotherapy among adults in the United States, 1975-2008.
abstract: 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 426068 adults initially treated with chemotherapy for first primary malignancy (9 US population-based cancer registries, 1975-2008), we identified 801 tAML cases, 4.70 times more than expected in the general population (P < .001). Over time, tAML risks increased after chemotherapy for non-Hodgkin lymphoma (n = 158; Poisson regression Ptrend < .001), declined for ovarian cancer (n = 72; Ptrend < .001), myeloma (n = 62; Ptrend = .02), and possibly lung cancer (n = 65; Ptrend = .18), and were significantly heterogeneous for breast cancer (n = 223; Phomogeneity = .005) and Hodgkin lymphoma (n = 58; Phomogeneity = .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 in 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 with time, consistent with changing treatment practices and differential leukemogenicity of specific therapies. tAML risks should be weighed against the benefits of chemotherapy, particularly for new agents and new indications for standard agents.
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
authors: Lindsay M
authors: LM
authors: Morton
authors: Graça M
authors: GM
authors: Dores
authors: Margaret A
authors: MA
authors: Tucker
authors: Clara J
authors: CJ
authors: Kim
authors: Kenan
authors: K
authors: Onel
authors: Ethel S
authors: ES
authors: Gilbert
authors: Joseph F
authors: JF
authors: Fraumeni
authors: Rochelle E
authors: RE
authors: Curtis
mesh_terms: D000208:Acute Disease; D000328:Adult; D000367:Age Factors; D000970:Antineoplastic Agents / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000139:chemically induced* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D016012:Poisson Distribution; D012044:Regression Analysis; D018570:Risk Assessment / Q000706:statistics & numerical data / Q000639:trends; D012307:Risk Factors; D018426:SEER Program / Q000706:statistics & numerical data* / Q000639:trends; D013997:Time Factors; D014481:United States / Q000453:epidemiology
chemical_list: D000970:Antineoplastic Agents