title: Impact of Conditioning Regimen on Outcomes for Children with Acute Myeloid Leukemia Undergoing Transplantation in First Complete Remission. An Analysis on Behalf of the Pediatric Disease Working Party of the European Group for Blood and Marrow Transplantation.
abstract: Hematopoietic stem cell transplantation (HSCT) represents the cornerstone of treatment in pediatric high-risk and relapsed acute myeloid leukemia (AML). The aim of the present study was to compare outcomes of pediatric patients with AML undergoing HSCT using 3 different conditioning regimens: total body irradiation (TBI) and cyclophosphamide (Cy); busulfan (Bu) and Cy; or Bu, Cy, and melphalan (Mel). In this retrospective study, registry data for patients > 2 and <18 years age undergoing matched allogeneic HSCT for AML in first complete remission (CR1) in 204 European Group for Blood and Marrow Transplantation centers between 2000 and 2010 were analyzed. Data were available for 631 patients; 458 patients received stem cells from a matched sibling donor and 173 from a matched unrelated donor. For 440 patients, bone marrow was used as stem cell source, and 191 patients received peripheral blood stem cells. One hundred nine patients received TBICy, 389 received BuCy, and 133 received BuCyMel as their preparatory regimen. Median follow-up was 55 months. Patients receiving BuCyMel showed a lower incidence of relapse at 5 years (14.7% versus 31.5% in BuCy versus 30% in TBICy, P < .01) and higher overall survival (OS) (76.6% versus 64% versus 64.5%, P = .04) and leukemia-free survival (LFS) (74.5% versus 58% versus 61.9%, P < .01), with a comparable nonrelapse mortality (NRM) (10.8% versus 10.5% versus 8.1%, P = .79). Acute graft-versus-host disease (GVHD) grades III and IV but not chronic GVHD, was higher in patients receiving BuCyMel. Older age at HSCT had an adverse impact on NRM and the use of peripheral blood as stem cell source was associated with increased chronic GVHD and NRM as well as lower LFS and OS. Among pediatric patients receiving HSCT for AML in CR1, the use of BuCyMel conditioning proved superior to TBICy and BuCy in reducing relapse and improving LFS.
authors.affiliation: Bone Marrow Transplant Department, Great Ormond Street Hospital, London, United Kingdom. Electronic address: Giovanna.Lucchini@gosh.nhs.uk.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lucchini
authors.affiliation: BMT Statistical Unit, European Group for Blood and Marrow Transplantation Office, Universite' Pierre et Marie Curie, Paris, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Labopin
authors.affiliation: BMT Statistical Unit, European Group for Blood and Marrow Transplantation Office, Universite' Pierre et Marie Curie, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Beohou
authors.affiliation: BMT Statistical Unit, European Group for Blood and Marrow Transplantation Office, Universite' Pierre et Marie Curie, Paris, France.
authors.forename: Arnauld
authors.initials: A
authors.lastname: Dalissier
authors.affiliation: Hemato-immunology Department, Hôpital Robert Debre, Paris, France.
authors.forename: Jean Hughes
authors.initials: JH
authors.lastname: Dalle
authors.affiliation: Paediatric Haematology/Oncology Department, Bristol Royal Hospital for Children, Bristol, United Kingdom.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Cornish
authors.affiliation: Pediatric Hematology-Oncology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Zecca
authors.affiliation: Bone Marrow Transplant Department, Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Sujith
authors.initials: S
authors.lastname: Samarasinghe
authors.affiliation: Haematology Department, Royal Hospital for Sick Children, Glasgow, United Kingdom.
authors.forename: Brenda
authors.initials: B
authors.lastname: Gibson
authors.affiliation: Pediatric Hematology-Oncology Department, IRCCS Bambino Gesu' Children Hospital, Rome, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.affiliation: Pediatric Hematology and Oncology Department, Institut d'Hématologie et d'Oncologie Pédiatriqu, Lyon, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Bertrand
authors.affiliation: Bone Marrow and Stem Cell Transplantation Department, King Hussein Cancer Centre, Amman, Jordan.
authors.forename: Fawzi
authors.initials: F
authors.lastname: Abdel-Rahman
authors.affiliation: Hematology/Transplantation Department, Hôpital St. Louis, Paris, France.
authors.forename: Gerald
authors.initials: G
authors.lastname: Socie
authors.affiliation: Hematology/Immunology/SCT Department, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Sundin
authors.affiliation: Pediatrics Department, Division of Immuno-Hematology and Stem Cell Transplantation Leiden University Hospital, The Netherlands.
authors.forename: Arjan
authors.initials: A
authors.lastname: Lankester
authors.affiliation: Paediatric Haematology & Oncology Department, University Hospital Motol, Prague, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Sedlacek
authors.affiliation: Hematology Department, Centre Pierre et Marie Curie, Alger, Algeria.
authors.forename: Rose Marie
authors.initials: RM
authors.lastname: Hamladji
authors.affiliation: Paediatrics and Adolescent Medicine Department, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Carsten
authors.initials: C
authors.lastname: Heilmann
authors.affiliation: Hematology and Transplantology Department, Saint Petersburg State Medical Pavlov University, Ratsa Gorbacheva Memorial Children's Institute, St. Petersburg, Russia.
authors.forename: Boris
authors.initials: B
authors.lastname: Afanasyev
authors.affiliation: Stem Cell Transplantation Department, University College Hospital, London, United Kingdom.
authors.forename: Rachel
authors.initials: R
authors.lastname: Hough
authors.affiliation: Stem Cell Transplantation Department, St. Anna Kinderspital, Vienna, Austria.
authors.forename: Cristina
authors.initials: C
authors.lastname: Peters
authors.affiliation: Stem Cell Transplantation and Immunology Department, Universitätsklinikum Frankfurt, Goethe-Universität, Frankfurt am Main, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bader
authors.affiliation: Bone Marrow Transplant Department, Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Veys
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002066:Busulfan / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D005060:Europe; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D012008:Recurrence; D012042:Registries; D012074:Remission Induction; D012189:Retrospective Studies; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods* / Q000401:mortality; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014916:Whole-Body Irradiation
chemical_list: D003520:Cyclophosphamide; D002066:Busulfan; D008558:Melphalan