title: Impact of in vivo T cell depletion in HLA-identical allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission conditioned with a fludarabine iv-busulfan myeloablative regimen: a report from the EBMT Acute Leukemia Working Party.
abstract: The impact of the use of anti-thymocyte globulin (ATG) in allogeneic stem cell transplantation performed with HLA-identical sibling donors following fludarabine and 4 days intravenous busulfan myeloablative conditioning regimen has been poorly explored.
  
  
  
  We retrospectively analyzed 566 patients who underwent a first HLA-identical allogeneic stem cell transplantation with this conditioning regimen for acute myeloid leukemia in first complete remission between 2006 and 2013 and compared the outcomes of 145 (25.6%) patients who received ATG (ATG group) to 421 (74.4%) who did not (no-ATG group). The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate.
  
  
  
  Patients in the ATG group were older, received more frequently peripheral blood stem cell grafts from older donors, and were transplanted more recently. With a median follow-up of 19 months, patients in the ATG group had reduced 2-year cumulative incidence of chronic graft-versus-host disease (GVHD) (31 vs. 52%, p = 0.0002) and of its extensive form (8 vs. 26%, p < 0.0001) but similar relapse incidence (22 vs. 27%, p = 0.23) leading to improved GVHD and relapse-free survival (GRFS) (60 vs. 40%, p = 0.0001). In multivariate analyses, the addition of ATG was independently associated with lower chronic GVHD (HR = 0.46, p = 0.0001), improved leukemia-free survival (HR = 0.67, p = 0.027), overall survival (HR = 0.65, p = 0.027), and GRFS (HR = 0.51, p = 4 × 10-5). Recipient age above 50 years was the only other factor associated with worse survivals.
  
  
  
  These results suggest that the use of ATG with fludarabine and 4 days intravenous busulfan followed by HLA-identical sibling donor allogeneic stem cell transplantation for acute myeloid leukemia improves overall transplant outcomes due to reduced incidence of chronic GVHD without increased relapse risk.
authors.affiliation: Service d'Hématologie et de Médecine interne, Hôpital Brabois, CHRU Nancy, Nancy, France. mt_rubio@hotmail.com.|IMoPA, CNRS UMR 7365, Nancy, France. mt_rubio@hotmail.com.|Université de Lorraine, Nancy, France. mt_rubio@hotmail.com.
authors.forename: Marie Thérèse
authors.initials: MT
authors.lastname: Rubio
authors.affiliation: Service d'Hématologie et de Médecine interne, Hôpital Brabois, CHRU Nancy, Nancy, France. m.daveni-piney@chru-nancy.fr.|IMoPA, CNRS UMR 7365, Nancy, France. m.daveni-piney@chru-nancy.fr.|Université de Lorraine, Nancy, France. m.daveni-piney@chru-nancy.fr.
authors.forename: Maud
authors.initials: M
authors.lastname: D'Aveni-Piney
authors.affiliation: ALWP Office, Hôpital Saint Antoine, Paris, France.|Service d'Hématologie et de Thérapie Cellulaire, Hôpital Saint Antoine, Paris, France.|INSERM UMR 938, Paris, France.|Université Pierre et Marie Curie, Paris, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Labopin
authors.affiliation: Service Hématologie Greffe de Moëlle, Centre Pierre et Marie Curie, Alger, Algeria.
authors.forename: Rose-Marie
authors.initials: RM
authors.lastname: Hamladji
authors.affiliation: Servicio de Hematologia, Hospital Universitario La Fe, Valencia, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sanz
authors.affiliation: Programme de Transplantation and Therapie Cellulaire, Centre de Recherche en Cancérologie de Marseille, Institut Paoli Calmettes, Marseille, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Blaise
authors.affiliation: Hematology Division, BMT Unit, Hematology Reserach Laboratory, Training and Medical, Baskent University Hospital, Adana, Turkey.
authors.forename: Hakan
authors.initials: H
authors.lastname: Ozdogu
authors.affiliation: Hopital Jean Minjoz, Service d`Hématologie, Besancon, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Daguindeau
authors.affiliation: Servicio de Hematología-Hemoterapia, Hospital U. Marqués de Valdecilla, Santander, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Richard
authors.affiliation: Dipartimento di Ematologia, Medicina Trasfusionale e Biotecnologie, Ospedale Civile, Pescara, Italy.
authors.forename: Stella
authors.initials: S
authors.lastname: Santarone
authors.affiliation: Azienda Ospedaliera, Centro Unico Regionale Trapianti, Reggio, Calabria, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Irrera
authors.affiliation: Hôpital HURIEZ UAM allo-CSH, CHRU, Lille, France.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Yakoub-Agha
authors.affiliation: Hematology and BMT Department, Beilinson Hospital, Petach-Tikva, Israel.
authors.forename: Moshe
authors.initials: M
authors.lastname: Yeshurun
authors.affiliation: Sección de Transplante de Medula Osea, Hospital Gregorio Marañón, Madrid, Spain.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Diez-Martin
authors.affiliation: ALWP Office, Hôpital Saint Antoine, Paris, France.|Service d'Hématologie et de Thérapie Cellulaire, Hôpital Saint Antoine, Paris, France.|INSERM UMR 938, Paris, France.|Université Pierre et Marie Curie, Paris, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.affiliation: ALWP Office, Hôpital Saint Antoine, Paris, France.|Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Bipin N
authors.initials: BN
authors.lastname: Savani
authors.affiliation: ALWP Office, Hôpital Saint Antoine, Paris, France.|Université Pierre et Marie Curie, Paris, France.|Division of Hematology, Chaim Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D002066:Busulfan / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D006680:HLA Antigens; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006648:Histocompatibility / Q000276:immunology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D047589:Leukocyte Reduction Procedures; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use; D012189:Retrospective Studies; D013601:T-Lymphocytes; D019172:Transplantation Conditioning / Q000379:methods; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D006680:HLA Antigens; D019653:Myeloablative Agonists; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine
keywords: Acute myeloid leukemia; Allogeneic stem cell transplantation; GRFS; Graft-versus-host disease; HLA-matched related donor; In vivo T cell depletion; Relapse incidence