A Growing Consequence of Cancer Therapy: What tAML Means for Patients and Pharmacists

Understanding Therapy-Related Acute Myeloid Leukemia

Therapy-related acute myeloid leukemia (tAML) is an increasingly recognized complication of modern cancer treatments. Emerging population-based data from Japan found that the occurrence of tAML has nearly tripled over the past 3 decades, with a growing proportion of cases among all AML diagnoses.¹ These findings emphasize an important and evolving risk associated with improved cancer survival.

Therapy-related AML is a subtype of AML that develops as a direct consequence of prior cytotoxic cancer therapy, including chemotherapy or radiation, unlike de novo AML, which occurs with no known cause.² tAML is typically associated with older age at diagnosis, poorer cytogenetic profiles, lower response rates to treatment, and shorter overall survival compared with de novo AML.²^,³ Certain chemotherapy agents (alkylating agents and topoisomerase II inhibitors) are strongly associated with the development of tAML due to their ability to damage DNA.³ This damage can lead to malignant transformation of hematopoietic stem cells over time.

Why Is tAML Increasing?

The increased prevalence of tAML is linked to improvements in cancer care. As more patients survive their primary cancers, the potential development of therapy-related complications, including secondary malignancies such as tAML, myelodysplastic syndromes, and occasionally other treatment-associated cancers, increases.⁴ Other contributing factors include the aging population. Older adults are more susceptible to tAML because their bone marrow cannot successfully repair therapy-related DNA damage, and age-related mutations increase the likelihood of leukemia developing after cytotoxic therapy.¹

The early detection of primary cancers is another contributing factor, as more patients are identified and treated at earlier stages of disease. In addition, broader access to cancer therapies allows more patients to receive potentially life-saving treatments. Although this leads to success in oncology, more survivors are exposed to cytotoxic therapy, creating a larger population at risk for developing tAML.¹ Newer treatments, such as immunotherapy, may reduce some therapy-related toxicities. However, the long-term impact of these therapies on secondary malignancies, including tAML, remains unclear.¹

Key Findings

Kishimoto and colleagues conducted a population-based study using data from the Osaka Cancer Registry between 1990 and 2020.¹ The study included 9841 total AML cases, of which 636 (6.5%) were classified as therapy-related AML.¹ The primary objective was to evaluate trends in incidence and identify changes in the types of primary cancers associated with tAML. tAML incidence increased from 0.13 to 0.36 per 100,000 people over the 30-year study period.¹ The proportion of tAML among all AML cases nearly doubled, and each decade was associated with a significant increase in incidence, with rates rising by approximately 28% every 10 years (incidence rate ratio, 1.28).¹ The most common prior cancers associated with tAML were hematologic malignancies (23.1%), followed by breast cancer (14.6%), colorectal cancer (11.5%), and gastric cancer (8.7%).¹ Patients with tAML were older at diagnosis than those with de novo AML, with a greater proportion between ages 60 and 74.¹

Pharmacist Implications

With the rising incidence of tAML, pharmacists play a crucial role in managing long-term treatment risks, monitoring therapy-related complications, and ensuring sound health decision-making. It is crucial to monitor patients who survive cancer for any potential delayed adverse effects, including cytopenias or any hematologic abnormalities that indicate tAML or other therapy-related malignancies. Keeping patients informed about the potential adverse effects associated with cytotoxic therapies can help ensure they seek the required follow-up care. Pharmacists also contribute to treatment planning by evaluating the leukemogenic potential of specific agents and supporting therapy selection that balances efficacy with long-term safety.

As oncology treatment strategies continue to evolve, including the increased use of targeted therapies and immunotherapy, pharmacists must stay informed on emerging evidence regarding secondary malignancy risk.

References

1. Kishimoto K, Nakata K, Shimadzu Kato M, et al. Increasing incidence and changing distribution of primary cancers in therapy-related acute myeloid leukemia: a population-based study in Osaka, Japan, 1990–2020. Cancer. Published online April 6, 2026. doi:10.1002/cncr.70316

2. Godley LA, Larson RA. Therapy-related myeloid leukemia. Semin Oncol. 2008;35(4):418-429. doi:10.1053/j.seminoncol.2008.04.012

3. Döhner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia. N Engl J Med. 2015;373(12):1136-1152. doi:10.1056/NEJMra1406184

4. Morton LM, Dores GM, Tucker MA, et al. Evolving risk of therapy-related acute myeloid leukemia following cancer chemotherapy among adults in the United States. Blood. 2013;121(15):2996-3004. doi:10.1182/blood-2012-08-448068