title: Occurrence of secondary malignancies in chronic myeloid leukemia during therapy with imatinib mesylate-single institution experience.
abstract: BACKGROUND
  Imatinib mesylate (IM) remains the treatment of choice for chronic myeloid leukemia (CML) showing a remarkable efficacy and offers a perspective for long disease-free survival. Due to prolonged administration of IM, the questions about the possible impact on the development of secondary malignancies (SM) are raised.
  
  
  OBJECTIVE
  To investigate the incidence and clinical outcome of secondary malignancies during IM therapy for CML.
  
  
  METHODS
  The records of 221 CML patients treated with IM between 2003-2013 in a single institution were reviewed. The Poisson regression model was used to estimate the relative risks for SM and death in CML patients.
  
  
  RESULTS
  Secondary malignancies developed in eight out of the 221 patients (3.6%) receiving IM for a median of 61 months (range, 10-137 months). Female/male ratio was 5/3. Two patients were diagnosed with their CML at accelerated phase whereas 6 had chronic phase. The median age at IM initiation was 58 years (range, 31-72 years). Five of these 8 SM patients received IM after other treatments failure: interferon α (n=5), hydroxyurea (n=4) and cytarabine (n=1). Three patients received IM as a frontline therapy. All patients were on IM at 400mg daily at SM occurrence. The therapy for SM included surgery (n=3), chemotherapy only (n=3), and chemotherapy followed by radiotherapy (n=1). One patient did not receive treatment due to disseminated disease. All CML patients were in hematologic and complete cytogenetic response (CCR) at the time of SM development. All of them also met the criteria for major molecular response (BCR-ABL(IS) ≤0.1%). They continued their IM while receiving treatment for SM. Among eight patients with SM, five patients are alive and remain in CCR on IM whereas three patients died due to SM. The risks for SM development as well as death due to SM in CML patients were not statistically increased if compared to age-adjusted population.
  
  
  CONCLUSIONS
  The association between IM therapy for CML and SM development has not been found.
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Silesian Medical University, Katowice, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Helbig
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Silesian Medical University, Katowice, Poland.
authors.forename: Grażyna
authors.initials: G
authors.lastname: Bober
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Silesian Medical University, Katowice, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Seweryn
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Silesian Medical University, Katowice, Poland.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Wichary
authors.affiliation: Department of Statistics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Tukiendorf
authors.affiliation: Student Research Group, Department of Hematology and Bone Marrow Transplantation, Silesian Medical University, Katowice, Poland.
authors.forename: Lech
authors.initials: L
authors.lastname: Sedlak
authors.affiliation: Student Research Group, Department of Hematology and Bone Marrow Transplantation, Silesian Medical University, Katowice, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Oleksy
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Silesian Medical University, Katowice, Poland.
authors.forename: Sławomira
authors.initials: S
authors.lastname: Kyrcz-Krzemień