title: Tyrosine kinase inhibitors improve long-term outcome of allogeneic hematopoietic stem cell transplantation for adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia.
abstract: This study aimed to determine the impact of tyrosine kinase inhibitors given pre- and post-allogeneic stem cell transplantation on long-term outcome of patients allografted for Philadelphia chromosome-positive acute lymphoblastic leukemia. This retrospective analysis from the EBMT Acute Leukemia Working Party included 473 de novo Philadelphia chromosome-positive acute lymphoblastic leukemia patients in first complete remission who underwent an allogeneic stem cell transplantation using a human leukocyte antigen-identical sibling or human leukocyte antigen-matched unrelated donor between 2000 and 2010. Three hundred and ninety patients received tyrosine kinase inhibitors before transplant, 329 at induction and 274 at consolidation. Kaplan-Meier estimates of leukemia-free survival, overall survival, cumulative incidences of relapse incidence, and non-relapse mortality at five years were 38%, 46%, 36% and 26%, respectively. In multivariate analysis, tyrosine-kinase inhibitors given before allogeneic stem cell transplantation was associated with a better overall survival (HR=0.68; P=0.04) and was associated with lower relapse incidence (HR=0.5; P=0.01). In the post-transplant period, multivariate analysis identified prophylactic tyrosine-kinase inhibitor administration to be a significant factor for improved leukemia-free survival (HR=0.44; P=0.002) and overall survival (HR=0.42; P=0.004), and a lower relapse incidence (HR=0.40; P=0.01). Over the past decade, administration of tyrosine kinase inhibitors before allogeneic stem cell transplantation has significantly improved the long-term allogeneic stem cell transplantation outcome of adult Philadelphia chromosome-positive acute lymphoblastic leukemia. Prospective studies will be of great interest to further confirm the potential benefit of the prophylactic use of tyrosine kinase inhibitors in the post-transplant setting.
authors.affiliation: Université Pierre et Marie Curie, Paris, France INSERM, UMRs 938, Paris, France Service d'Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint Antoine, APHP, Paris, France CHRU Hôtel-Dieu, Nantes, France.
authors.forename: Eolia
authors.initials: E
authors.lastname: Brissot
authors.affiliation: Université Pierre et Marie Curie, Paris, France INSERM, UMRs 938, Paris, France Service d'Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint Antoine, APHP, Paris, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Labopin
authors.affiliation: University Hospital Leuven, Leuven, Belgium.
authors.forename: Marielle M
authors.initials: MM
authors.lastname: Beckers
authors.affiliation: Hôpital Saint Louis, Paris, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Socié
authors.affiliation: Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rambaldi
authors.affiliation: Helsinki University Central Hospital, Finland.
authors.forename: Liisa
authors.initials: L
authors.lastname: Volin
authors.affiliation: University of Freiburg Medical Center, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Finke
authors.affiliation: Lund University Hospital, Sweden.
authors.forename: Stig
authors.initials: S
authors.lastname: Lenhoff
authors.affiliation: University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
authors.affiliation: VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Gert J
authors.initials: GJ
authors.lastname: Ossenkoppele
authors.affiliation: Queen Elizabeth Hospital, Birmingham, UK.
authors.forename: Charles F
authors.initials: CF
authors.lastname: Craddock
authors.affiliation: CHRU Lille, France.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Yakoub-Agha
authors.affiliation: Ankara University, Faculty of Medicine, Ankara, Turkey.
authors.forename: Günhan
authors.initials: G
authors.lastname: Gürman
authors.affiliation: Nottingham University Hospital, Nottingham, UK.
authors.forename: Nigel H
authors.initials: NH
authors.lastname: Russell
authors.affiliation: King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Aljurf
authors.affiliation: The Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Potter
authors.affiliation: Chaim Sheba Medical Center, Tel Hasomer, Israel.
authors.forename: Armon
authors.initials: A
authors.lastname: Nagler
authors.affiliation: Goethe-University Frankfurt, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Ottmann
authors.affiliation: Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Cornelissen
authors.affiliation: Hospital Clinic Institut d'investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Esteve
authors.affiliation: Université Pierre et Marie Curie, Paris, France INSERM, UMRs 938, Paris, France Service d'Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint Antoine, APHP, Paris, France mohamad.mohty@inserm.fr.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012074:Remission Induction; D012189:Retrospective Studies; D035781:Siblings; D016019:Survival Analysis; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors