Incidence and Risk of Therapy-Related Myeloid Neoplasms in Non-Myeloid Hematological Malignancies: A National Population-Based Matched Cohort Study

• Published in: Blood 2024-11, Vol.144, p.5179-5179
• Main Authors: Hansen, Dennis Lund, Lauritsen, Tine Bichel, Norgaard, Jan M, Dalton, Susanne, Gronbaek, Kirsten, El-Galaly, Tarec Christoffer, Østgård, Lene Sofie Granfeldt
• Format: Article
• Language: English
• ISSN: 0006-4971
• DOI: 10.1182/blood-2024-210582

Introduction Therapy-related myeloid neoplasm (tMN) is a serious late-effect following cancer treatment affecting long-term survival. However, risk factors for tMN after non-myeloid hematological malignancies (nMHM) are not well understood. The present study examined the risk of myeloid neoplasms (MN) among patients diagnosed with nMHM and treated with different types of cancer treatment. Materials and Methods We conducted a nationwide, population-based matched cohort study combining Danish health and quality registries. The Danish health care system is tax-funded and all inhabitants are assigned a unique civil registration number enabling linkage of all administrative data enabling complete follow-up. We included patients ≥18 years with a first-time diagnosis of nMHM, between January 2004 and December 2016. Each patient was year-age-sex-matched in a 1:10 ratio to cancer-free individuals from the general population. We used date of nMHM diagnosis as index date for patients and their matched comparators. Primary outcomes were incident MN (AML, MDS, and CMML) between January 2004 to July 2018. All patients and matched comparators were followed until MN/tMN, emigration, death, or end-of-follow-up (July 2018). We quantified the risk of MN by cancer treatment into the following categories 1) no cytotoxic therapy (e.g. watch and wait or surgery only), 2) radiotherapy, 3) chemotherapy, and 4) radio-chemotherapy. Treatment category could only change from a less to a more intensive treated category during follow-up. We used Cox regression analyses to estimate risk of MN/tMN, controlling for matching factors per design. We further estimated 10-year cumulative incidence proportions for MN/tMN. Results were given by disease (non-Hodgkin (NHL) and Hodgkin lymphomas (HL), multiple myeloma (MM) and lymphatic leukemia), crude and adjusted for Charlson Comorbidity Index, age, sex, and calendar year. We performed sensitivity analyses to assess robustness of results. Results We identified 490 MN/tMN cases among 44,478 nMHM patients and 510 MN cases among 443,178 comparators. Median age at first diagnosis of MN varied from 45 years in HL to 70 years in MM patients. Most cases of MN/tMN among nHMN patients were preceded by chemotherapy or combined radio-chemotherapy. The overall 10-year cumulative incidence of MN/tMN amongst patients ranged from 0.76 to 5.19% with highest risks in patients treated with cytotoxic therapy. Amongst matched comparators, the risk ranged from 0.12-0