title: Secondary malignancies in chronic myeloid leukemia patients after imatinib-based treatment: long-term observation in CML Study IV.
abstract: Treatment of chronic myeloid leukemia (CML) has been profoundly improved by the introduction of tyrosine kinase inhibitors (TKIs). Long-term survival with imatinib is excellent with a 8-year survival rate of ∼88%. Long-term toxicity of TKI treatment, especially carcinogenicity, has become a concern. We analyzed data of the CML study IV for the development of secondary malignancies. In total, 67 secondary malignancies were found in 64 of 1525 CML patients in chronic phase treated with TKI (n=61) and interferon-α only (n=3). The most common malignancies (n⩾4) were prostate, colorectal and lung cancer, non-Hodgkin's lymphoma (NHL), malignant melanoma, non-melanoma skin tumors and breast cancer. The standardized incidence ratio (SIR) for all malignancies excluding non-melanoma skin tumors was 0.88 (95% confidence interval (0.63-1.20)) for men and 1.06 (95% CI 0.69-1.55) for women. SIRs were between 0.49 (95% CI 0.13-1.34) for colorectal cancer in men and 4.29 (95% CI 1.09-11.66) for NHL in women. The SIR for NHL was significantly increased for men and women. An increase in the incidence of secondary malignancies could not be ascertained. The increased SIR for NHL has to be considered and long-term follow-up of CML patients is warranted, as the rate of secondary malignancies may increase over time.
authors: III. Medizinische Klinik, Universitätsmedizin, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany.
authors: M B
authors: MB
authors: Miranda
authors: Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie, Ludwig-Maximilians-Universität, München, Germany.
authors: M
authors: M
authors: Lauseker
authors: III. Medizinische Klinik, Universitätsmedizin, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany.
authors: M-P
authors: MP
authors: Kraus
authors: III. Medizinische Klinik, Universitätsmedizin, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany.
authors: U
authors: U
authors: Proetel
authors: III. Medizinische Klinik, Universitätsmedizin, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany.
authors: B
authors: B
authors: Hanfstein
authors: III. Medizinische Klinik, Universitätsmedizin, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany.
authors: A
authors: A
authors: Fabarius
authors: Universitätsklinik für Hämatologie und Hämatologisches Zentrallabor, Inselspital, Bern, Switzerland.
authors: G M
authors: GM
authors: Baerlocher
authors: Klinik für Hämatologie, Universitätsspital, Basel, Switzerland.
authors: D
authors: D
authors: Heim
authors: II. Medizinische Klinik, Universitätsklinikum Eppendorf, Hamburg, Germany.
authors: D K
authors: DK
authors: Hossfeld
authors: Medizinische Klinik und Poliklinik III, Klinikum der Ludwig-Maximilians-Universität, München, Germany.
authors: H-J
authors: HJ
authors: Kolb
authors: Medizinische Klinik 5, Universitätsklinikum, Erlangen, Germany.
authors: S W
authors: SW
authors: Krause
authors: Klinik für Hämatologie, Onkologie, Immunologie, Palliativmedizin, Infektiologie und Tropenmedizin, Klinikum Schwabing, München, Germany.
authors: C
authors: C
authors: Nerl
authors: Medizinische Klinik IV, Uniklinik RWTH, Aachen Germany.
authors: T H
authors: TH
authors: Brümmendorf
authors: Zentrum für ambulante Hämatologie und Onkologie, Bonn, Germany.
authors: W
authors: W
authors: Verbeek
authors: Klinik für Knochenmarktransplantation und Hämatologie/Onkologie, Klinikum, Idar-Oberstein, Germany.
authors: A A
authors: AA
authors: Fauser
authors: Klinik für Hämatologie, Onkologie und Palliativmedizin, Klinikum, Kempten, Germany.
authors: O
authors: O
authors: Prümmer
authors: Medizinische Klinik 2, Klinikum Mittelbaden, Standort Balg, Baden-Baden, Germany.
authors: K
authors: K
authors: Neben
authors: Klinik für Onkologie/Hämatologie, Kantonsspital, St Gallen, Switzerland.
authors: U
authors: U
authors: Hess
authors: Innere Medizin 1, Klinikum Mutterhaus der Borromäerinnen, Trier, Germany.
authors: R
authors: R
authors: Mahlberg
authors: Mannheimer Onkologie Praxis, Mannheim, Germany.
authors: C
authors: C
authors: Plöger
authors: Medizinische Klinik III, Krankenhaus, Düren, Germany.
authors: M
authors: M
authors: Flasshove
authors: Praxis für Innere Medizin, Nephrologie, Hämatologie und Onkologie, Trier, Germany.
authors: B
authors: B
authors: Rendenbach
authors: III. Medizinische Klinik, Universitätsmedizin, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany.
authors: W-K
authors: WK
authors: Hofmann
authors: III. Medizinische Klinik, Universitätsmedizin, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany.
authors: M C
authors: MC
authors: Müller
authors: Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie, Ludwig-Maximilians-Universität, München, Germany.
authors: M
authors: M
authors: Pfirrmann
authors: Klinik für Innere Medizin II, Universitätsklinikum, Jena, Germany.
authors: A
authors: A
authors: Hochhaus
authors: Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie, Ludwig-Maximilians-Universität, München, Germany.
authors: J
authors: J
authors: Hasford
authors: III. Medizinische Klinik, Universitätsmedizin, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany.
authors: R
authors: R
authors: Hehlmann
authors: III. Medizinische Klinik, Universitätsmedizin, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany.
authors: S
authors: S
authors: Saußele
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015179:Colorectal Neoplasms / Q000139:chemically induced; D005500:Follow-Up Studies; D000068877:Imatinib Mesylate / Q000009:adverse effects / Q000627:therapeutic use; D015994:Incidence; D016898:Interferon-alpha / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000150:complications / Q000188:drug therapy; D008228:Lymphoma, Non-Hodgkin / Q000139:chemically induced; D016609:Neoplasms, Second Primary / Q000139:chemically induced; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D012737:Sex Factors
chemical_list: D000068877:Imatinib Mesylate; D016898:Interferon-alpha; D047428:Protein Kinase Inhibitors