title: Second malignancies following treatment of chronic myeloid leukaemia in the tyrosine kinase inhibitor era.
abstract: Given that tyrosine kinase inhibitors (TKIs) have dramatically improved the survival of patients with chronic myeloid leukaemia (CML), we were interested in examining the possible risk of long-term adverse events, such as the emergence of other neoplasms. Therefore, we studied the development of second malignancies in 868 patients diagnosed with CML between 2002 and 2011 using the Swedish CML register, cross-linked to the Swedish Cancer register. With a median follow-up of 3·7 (range 0-9·9) years, 65 (7·5%) patients developed 75 second malignancies (non-haematological), 52 of which were of the invasive type. Compared to expected rates in the background population, the risk of second malignancies was higher in the CML cohort, with a standardized incidence ratio (SIR) of 1·52 (95% CI 1·13-1·99). The SIR before and after the second year following diagnosis of CML was 1·58 and 1·47, respectively. Among specific cancer types, gastrointestinal and nose and throat cancer were significantly increased. Founded on a population-based material, our results indicate that CML patients treated in the TKI era are at an increased risk of developing a second malignancy, with indications that this risk may more likely be linked to CML itself rather than to the TKI treatment.
authors.affiliation: Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Gunnarsson
authors.affiliation: Department of Haematology, Karolinska University Hospital, Stockholm, Sweden.|Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Leif
authors.initials: L
authors.lastname: Stenke
authors.affiliation: Department of Medical Science and Division of Haematology, University Hospital, Uppsala, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Höglund
authors.affiliation: Regional Cancer Centre, Uppsala-Örebro, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Sandin
authors.affiliation: Department of Haematology, Karolinska University Hospital, Stockholm, Sweden.|Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Björkholm
authors.affiliation: Department of Haematology, University Hospital, Linköping, Sweden.
authors.forename: Arta
authors.initials: A
authors.lastname: Dreimane
authors.affiliation: Regional Cancer Centre, Uppsala-Örebro, Sweden.|Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Lambe
authors.affiliation: Department of Haematology, University Hospital, Umeå, Sweden.
authors.forename: Berit
authors.initials: B
authors.lastname: Markevärn
authors.affiliation: Department of Medical Science and Division of Haematology, University Hospital, Uppsala, Sweden.
authors.forename: Ulla
authors.initials: U
authors.lastname: Olsson-Strömberg
authors.affiliation: Department of Haematology and Vascular Disorders, Skåne University Hospital, Lund, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Richter
authors.affiliation: Department of Haematology, Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Wadenvik
authors.affiliation: Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Wallvik
authors.affiliation: Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Själander
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015994:Incidence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000209:etiology*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D012042:Registries; D012306:Risk; D013548:Sweden / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors
keywords: chronic myeloid leukaemia; malignancy; treatment