title: Allogeneic and autologous bone marrow transplantation after consolidation therapy in high-risk acute myeloid leukemia in children. Towards a risk-oriented therapy.
abstract: OBJECTIVE
  Although chemotherapy in childhood acute myeloid leukemia (AML) has improved in the last decade, except for a group of better-risk patients (approximately one third), more than half the other patients relapse. The main objective of this study was to evaluate the results obtained with bone marrow transplants, either allogeneic (allo-BMT) or autologous (auto-BMT), following two intensive consolidation courses in a series of children with high-risk (HR) AML according to morphologic and early-response BFM criteria. A second objective was to compare the results of auto-BMT with those of allo-BMT.
  
  
  METHODS
  From April 1988 to May 2001, 79 children (< 15 years old) with de novo AML entered the prospective AML-88 trial in a single institution: 50 (63%) were qualified as having high-risk disease and are the subject of this study. After 1 or 2 induction courses, depending on early response, and two consolidations, patients with an HLA-identical sibling received an allo-BMT and all the others an auto-BMT. The conditioning regimen was cyclophosphamide and total body irradiation (TBI) in children over 3 years old and busulfan and etoposide in younger children. Bone marrow was purged with mafosfamide in auto-BMT and cyclosporine alone was given as graft-versus-host disease (GVHD) prophylaxis in allo-BMT.
  
  
  RESULTS
  At the end of the chemotherapy phase (induction and consolidation ), 46 of the 50 HR patients (92%) had attained complete remission (CR) after one (n=29), two (n=11) or three (n=6) courses; 2 more were in partial remission (PR) and 2 had died. The 48 patients in CR or PR received either an allo-BMT (17) or an auto-BMT (31). Hematologic reconstitution was significantly slower in auto-BMT recipients. Forty-one percent of patients who received allo-BMT suffered acute GVHD grades II-IV. Toxic deaths and relapse rates were 5.9% and 17.6%, respectively, in allo-BMT and 3.2% and 25.8%, respectively, in auto-BMT. Post-transplant 8-year event-free survival (EFS) was 74.5% (54-96) in allo-BMT and 74.2% (59-89) in auto-BMT. EFS and OS in all the series (50 patients) were 71% (59-83) and 73% (61-85), respectively, with a median follow-up of 7.2 years.
  
  
  CONCLUSIONS
  This study indicates that improved results in children with HR-AML can be obtained by either allo- or auto-BMT performed after two courses of intensive consolidation therapy provided good supportive therapy is given and reduced transplant -related mortality (TRM) is minimized.
authors.affiliation: Servicio de Hematologia y Oncologia, Area Infantil, Hospital Universitari Vall d'Hebron, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain. jortega.hmi@cs.vhebron.es
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Ortega
authors.forename: Cristina
authors.initials: C
authors.lastname: Díaz de Heredia
authors.forename: Teresa
authors.initials: T
authors.lastname: Olivé
authors.forename: Pilar
authors.initials: P
authors.lastname: Bastida
authors.forename: Anna
authors.initials: A
authors.lastname: Llort
authors.forename: Lluís
authors.initials: L
authors.lastname: Armadans
authors.forename: Marta
authors.initials: M
authors.lastname: Torrabadella
authors.forename: Lluís
authors.initials: L
authors.lastname: Massuet
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods / Q000401:mortality*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007951:Leukemia, Myeloid / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008297:Male; D011788:Quality of Life; D012306:Risk; D014182:Transplantation, Autologous / Q000401:mortality; D014184:Transplantation, Homologous / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents