Second primary non-myeloid malignancies following intensive treatment for adult acute myeloid leukaemia: a Danish population-based cohort study

Nanna Nørtoft Nielsen; Jonas Faartoft Jensen; Joachim Baech; Trine Trab; Tarec Christoffer El-Galaly; Claudia Schöllkopf; Andreas Due Ørskov; Hans Beier Ommen; Lene Sofie Granfeldt; Daniel Tuyet Kristensen; Marianne Tang Severinsen

doi:10.1016/j.lanepe.2024.101204

Second primary non-myeloid malignancies following intensive treatment for adult acute myeloid leukaemia: a Danish population-based cohort study

Lancet Reg Health Eur. 2024 Dec 30:50:101204. doi: 10.1016/j.lanepe.2024.101204. eCollection 2025 Mar.

Authors

Nanna Nørtoft Nielsen¹, Jonas Faartoft Jensen¹, Joachim Baech¹, Trine Trab^{1

2

3}, Tarec Christoffer El-Galaly^{1

4

5}, Claudia Schöllkopf^{2

6}, Andreas Due Ørskov⁷, Hans Beier Ommen⁸, Lene Sofie Granfeldt⁵, Daniel Tuyet Kristensen^{1

4}, Marianne Tang Severinsen^{1

4}

Affiliations

¹ Department of Haematology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.
² Department of Haematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
³ Biotech Research and Innovation Center (BRIC), University of Copenhagen, Copenhagen, Denmark.
⁴ Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
⁵ Department of Haematology, Odense University Hospital, Odense, Denmark.
⁶ Department of Haematology, Herlev Hospital, Herlev, Denmark.
⁷ Department of Haematology, Zealand University Hospital, Roskilde, Denmark.
⁸ Department of Haematology, Aarhus University Hospital, Aarhus, Denmark.

Abstract

Background: Second primary malignancies (SPMs) are a well-known, long-term complication of antineoplastic treatment. This nationwide cohort study examined the risk of non-myeloid SPMs in survivors of adult acute myeloid leukaemia (AML) treated with intensive chemotherapy and, in some cases, allogeneic stem cell transplantation (alloSCT), compared to a matched general population.

Methods: Patients with incident AML between 2000 and 2018, alive and aged 18-70 years two years after start of intensive chemotherapy, were included and matched 1:10 to comparators from the general Danish population on sex, age, and the Nordic Multimorbidity Index. Exclusion criteria were non-myeloid SPMs for both AML survivors and comparators.

Findings: A total of 750 AML survivors and 7500 comparators were followed for a median of 10.6 years. The hazard ratio (HR) of non-myeloid SPMs was 1.55 (95% confidence interval [CI] 1.27-1.89) for AML survivors compared to comparators, driven by non-melanoma skin cancer (HR 2.52, 95% CI 1.90-3.35), not of solid cancer (HR 1.14, 95% CI 0.87-1.49). The 10-year cumulative incidences of any non-myeloid SPM were 13.5% (95% CI 10.6-16.5%) in AML survivors and 11.9% (95% CI 11.1-12.8%) in matched comparators. Additionally, AML survivors consolidated with alloSCT had a higher hazard rate of non-myeloid SPMs compared to non-transplanted AML survivors (adjusted HR 1.50, 95% CI 1.00-2.26).

Interpretation: The increased rate of non-myeloid SPMs observed in this population-based cohort study of AML survivors was almost entirely driven by non-melanoma skin cancer and is thus outweighed by the importance of intensive chemotherapy.

Funding: Svend Andersen, Heinrich Kopps, and Karen Elise Jensen's Foundation.

Keywords: Acute myeloid leukaemia; Allogeneic stem-cell transplantation; Intensive chemotherapy; Long-term toxicities; Second primary non-myeloid malignancies.