title: No influence of BCR-ABL1 transcript types e13a2 and e14a2 on long-term survival: results in 1494 patients with chronic myeloid leukemia treated with imatinib.
abstract: OBJECTIVE
  The genomic break on the major breakpoint cluster region of chromosome 22 results in two BCR-ABL1 transcripts of different sizes, e14a2 and e13a2. Favorable survival probabilities of patients with chronic myeloid leukemia (CML) in combination with too small patient samples may yet have obstructed the observation of differences in overall survival of patients according to transcript type. To overcome potential power problems, overall survival (OS) probabilities and probabilities of CML-related death were analyzed in 1494 patients randomized to first-line imatinib treatment.
  
  
  METHODS
  OS probabilities and probabilities of dying of CML were compared using the log-rank or Gray test whichever was appropriate. Both tests were stratified for the EUTOS long-term survival score.
  
  
  RESULTS
  Between the groups with a single transcript, neither OS probabilities (stratified log-rank test: p = 0.106) nor probabilities of CML-related death were significantly different (stratified Gray test: p = 0.256). Regarding OS, the Cox hazard ratio (HR) of transcript type e13a2 (n = 565) to type e14a2 (n = 738) was 1.332 (95% CI 0.940-1.887). Considering probabilities of leukemia-related death, the corresponding subdistribution HR resulted in 1.284 (95% CI 0.758-2.176). Outcome did not change if patients with both transcripts (n = 191) were added to the 738 with type e14a2 only.
  
  
  CONCLUSIONS
  The prognostic association of transcript type and long-term survival outcome was weak and without clinical relevance. However, earlier reported differences in the rate and the depth of molecular response could be relevant for the chance of successfully discontinuing TKI treatment. The effect of transcript type on molecular relapse after discontinuation is unknown, yet.
authors.affiliation: Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie (IBE), Ludwig-Maximilians Universität, Marchioninistraße 15, 81377, Munich, Germany. pfi@ibe.med.uni-muenchen.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Pfirrmann
authors.affiliation: Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie (IBE), Ludwig-Maximilians Universität, Marchioninistraße 15, 81377, Munich, Germany.
authors.forename: Dobromira
authors.initials: D
authors.lastname: Evtimova
authors.affiliation: III. Medizinische Klinik, Universitätsmedizin Mannheim, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Saussele
authors.affiliation: Institute of Hematology and Oncology "L. and A. Seràgnoli", S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Castagnetti
authors.affiliation: Hematology Department, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Cervantes
authors.affiliation: Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Janssen
authors.affiliation: Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie (IBE), Ludwig-Maximilians Universität, Marchioninistraße 15, 81377, Munich, Germany.
authors.forename: Verena S
authors.initials: VS
authors.lastname: Hoffmann
authors.affiliation: Institute of Hematology and Oncology "L. and A. Seràgnoli", S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gugliotta
authors.affiliation: III. Medizinische Klinik, Universitätsmedizin Mannheim, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Hehlmann
authors.affiliation: Klinik für Innere Medizin II, Hematology/Oncology, Universitätsklinikum Jena, Jena, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.affiliation: Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie (IBE), Ludwig-Maximilians Universität, Marchioninistraße 15, 81377, Munich, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Hasford
authors.affiliation: Institute of Hematology and Oncology "L. and A. Seràgnoli", S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; C581634:BCR-ABL1 fusion protein, human; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl
keywords: BCR-ABL1 transcript type; Chronic myeloid leukemia; Overall survival; Probabilities of CML-related death; Prognosis