title: Improving results of autologous stem cell transplantation for Philadelphia-positive acute lymphoblastic leukaemia in the era of tyrosine kinase inhibitors: a report from the Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation.
abstract: BACKGROUND
  Outcome of Philadelphia-positive acute lymphoblastic leukaemia (Ph+ ALL) improved significantly with the introduction of tyrosine kinase inhibitors (TKIs). Autologous stem cell transplantation (ASCT) has never been considered a standard of care in this setting. The aim of our study was to analyse if results of ASCT improved in the era of TKIs.
  
  
  METHODS
  One-hundred and seventy-seven adults with Ph+ ALL treated with ASCT in first complete remission were analysed for the impact of year of transplantation on outcome. Additional analysis was performed including 32 patients for whom detailed data on the use of TKIs and the status of minimal residual disease were collected.
  
  
  RESULTS
  The probability of the overall survival (OS) at 3 years increased from 16% for transplants performed between 1996 and 2001 to 48% between 2002 and 2006 and 57% between 2007 and 2010 (P<.0001). Leukaemia-free survival (LFS) was 11%, 39% and 52%, respectively (P<.0001). Relapse incidence decreased from 70% to 45% and 45% (P=.01), respectively, while non-relapse mortality was 19%, 15% and 3% (P=.08). In a multivariate analysis, year of ASCT was the only independent factor influencing the risk of treatment failure (hazard ratio (HR)=0.37; P<.001). In a subgroup of 22 patients actually treated with TKIs and being in complete molecular remission at the time of ASCT, the LFS rate at 3 years was 65%.
  
  
  CONCLUSIONS
  Results of ASCT for Ph+ ALL improved significantly over time. Prospective, innovative studies are needed to verify the role of ASCT in this patient setting.
authors.affiliation: Dept. of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice Branch, Gliwice, Poland. Electronic address: sgiebel@io.gliwice.pl.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Giebel
authors.affiliation: Clinical Haematology and Cellular Therapy Department, Hospital Saint-Antoine, APHP, Paris, France; EBMT ALWP Office, Hospital Saint-Antoine, Paris, France; Universite Pierre et Marie Curie, Paris, France; INSERM UMRs 938, Paris, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Labopin
authors.affiliation: Clinical Haematology and Cellular Therapy Department, Hospital Saint-Antoine, APHP, Paris, France; EBMT ALWP Office, Hospital Saint-Antoine, Paris, France; Universite Pierre et Marie Curie, Paris, France; INSERM UMRs 938, Paris, France.
authors.forename: Norbert Claude
authors.initials: NC
authors.lastname: Gorin
authors.affiliation: Centre Hospitalier Universitaire Le Bocage, Dijon, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Caillot
authors.affiliation: Centre Hospitalier Universitaire Bordeaux, Hôpital Haut-Leveque, Pessac, France.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Leguay
authors.affiliation: Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Nicolaas
authors.initials: N
authors.lastname: Schaap
authors.affiliation: Centre Hospitalier Lyon Sud, Lyon, France.
authors.forename: Mauricette
authors.initials: M
authors.lastname: Michallet
authors.affiliation: Hospital St. Louis, Paris, France.
authors.forename: Herve
authors.initials: H
authors.lastname: Dombret
authors.affiliation: Clinical Haematology and Cellular Therapy Department, Hospital Saint-Antoine, APHP, Paris, France; EBMT ALWP Office, Hospital Saint-Antoine, Paris, France; Universite Pierre et Marie Curie, Paris, France; INSERM UMRs 938, Paris, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation; D018572:Disease-Free Survival; D005060:Europe; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000601:surgery*; D011505:Protein-Tyrosine Kinases / Q000627:therapeutic use*; D012189:Retrospective Studies; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D011505:Protein-Tyrosine Kinases
keywords: Acute lymphoblastic leukaemia; Autologous stem cell transplantation; Leukaemia-free survival; Philadelphia positive; Tyrosine kinase inhibitors