title: Effect of first-line treatment on second primary malignancies and Richter's transformation in patients with CLL.
abstract: This study aimed to assess the frequency of and the contributing factors for second primary malignancies (SPMs) and Richter's transformations (RTs) following first-line treatment of chronic lymphocytic leukemia within four phase II/III trials of the GCLLSG evaluating fludarabine (F) vs F+cyclophosphamide (FC), chlorambucil vs F, FC without or with rituximab, and bendamustine+R (BR). Among 1458 patients, 239 (16.4%) experienced either an SPM (N=191) or a RT (N=75). Solid tumors (N=115; 43.2% of all second neoplasias) appeared most frequently, followed by RTs (N=75; 28.2%). Patients showed a 1.23-fold increased risk of solid tumors in comparison to the age-matched general population from the German cancer registry. Age>65 (hazard ratio (HR) 2.1; P<0.001), male sex (HR 1.7; P=0.01), co-morbidities (HR 1.6; P=0.01) and number of subsequent treatments⩾1 (HR 12.1; P<0.001) showed an independent adverse prognostic impact on SPM-free survival. Serum thymidine kinase>10 U/l at trial enrollment (HR 3.9; P=0.02), non-response to first-line treatment (HR 3.6; P<0.001) and number of subsequent treatments⩾1 (HR 30.2; P<0.001) were independently associated with increased risk for RT.
authors.affiliation: Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Maurer
authors.affiliation: Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Langerbeins
authors.affiliation: Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Bahlo
authors.affiliation: Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Cramer
authors.affiliation: Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany.
authors.forename: A M
authors.initials: AM
authors.lastname: Fink
authors.affiliation: Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Pflug
authors.affiliation: Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Engelke
authors.affiliation: Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany.
authors.forename: J
authors.initials: J
authors.lastname: von Tresckow
authors.affiliation: Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Kovacs
authors.affiliation: Department of Internal Medicine III, University of Ulm, Ulm, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Stilgenbauer
authors.affiliation: Department of Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases and Tropical Medicine, Klinikum Schwabing, Munich, Germany.
authors.forename: C-M
authors.initials: CM
authors.lastname: Wendtner
authors.affiliation: Oncology Leer, Practice for Hematology and Oncology, Leer, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Müller
authors.affiliation: Second Department of Medicine, University Hospital of Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Ritgen
authors.affiliation: Department of Medicine III, University Hospital Großhadern/LMU München, Munich, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Seiler
authors.affiliation: Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Fischer
authors.affiliation: Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany.|Cluster of Excellence in Cellular Stress Responses in Aging-associated Diseases, Univeristy of Cologne, Cologne, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hallek
authors.affiliation: Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Eichhorst
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000069461:Bendamustine Hydrochloride / Q000008:administration & dosage / Q000627:therapeutic use; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D002699:Chlorambucil / Q000008:administration & dosage / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005858:Germany; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000188:drug therapy* / Q000401:mortality; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D002699:Chlorambucil; D003520:Cyclophosphamide; D000069461:Bendamustine Hydrochloride; D014740:Vidarabine; C024352:fludarabine