title: Expanding transplant options to patients over 50 years. Improved outcome after reduced intensity conditioning mismatched-unrelated donor transplantation for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the EBMT.
abstract: The outcome of patients undergoing HLA-matched unrelated donor allogeneic hematopoietic cell transplantation following reduced-intensity conditioning or myeloablative regimens is reported to be equivalent; however, it is not known if the intensity of the conditioning impacts outcomes after mismatched unrelated donor transplantation for acute myeloid leukemia. Eight hundred and eighty three patients receiving reduced-intensity conditioning were compared with 1041 myeloablative conditioning regimen recipients in the setting of mismatched unrelated donor transplantation. The donor graft was HLA-matched at 9/10 in 872 (83.8%) and at 8/10 in 169 (16.2%) myeloablative conditioning recipients, while in the reduced-intensity conditioning cohort, 754 (85.4%) and 129 (14.6%) were matched at 9/10 and 8/10 loci, respectively. Myeloablative conditioning regimen recipients were younger, 70% being <50 years of age compared to only 30% in the reduced-intensity conditioning group (P=0.0001). Significantly, more patients had secondary acute myeloid leukemia (P=0.04) and Karnofsky Performance Status score <90% (P=0.02) in the reduced-intensity conditioning group. Patients <50 and ≥50 years were analyzed separately. On multivariate analysis and after adjusting for differences between the two groups, reduced-intensity conditioning in patients age ≥50 years was associated with higher overall survival (HR 0.78; P=0.01), leukemia-free survival (HR 0.82; P=0.05), and decreased non-relapse mortality (HR 0.73; P=0.03). Relapse incidence (HR 0.91; P=0.51) and chronic graft-versus-host disease (HR 1.31; P=0.11) were, however, not significantly different. In patients <50 years old, there were no statistically significant differences in overall survival, leukemia-free survival, relapse incidence, non-relapse mortality, and chronic graft-versus-host-disease between the groups. Our study shows no significant outcome differences in patients younger than 50 years receiving reduced-intensity vs myeloablative conditioning regimens after mismatched unrelated donor transplantation. Furthermore, the data support the superiority of reduced-intensity conditioning regimens in older adults receiving transplants from mismatched unrelated donors.
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN, USA Acute Leukemia Working Party, EBMT Paris study office / CEREST-TC, France bipin.savani@vanderbilt.edu.
authors.forename: Bipin N
authors.initials: BN
authors.lastname: Savani
authors.affiliation: Acute Leukemia Working Party, EBMT Paris study office / CEREST-TC, France Department of Haematology, Saint Antoine Hospital, 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: University Hospital Eppendorf, Department of Stem cell Transplantation, Hamburg, Germany.
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
authors.affiliation: University of Freiburg, Department of Medicine -Hematology, Oncology, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Finke
authors.affiliation: Universitaetsklinikum Dresden, MedizinischeKlinik und Poliklinik I, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.affiliation: University Hospital Leipzig, Div. Hematology, Oncology and Hemostasiology, Germany.
authors.forename: Dietger
authors.initials: D
authors.lastname: Niederwieser
authors.affiliation: Helios-Klinikum Berlin-Buch, Dept. Hematology Berlin, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Schwerdtfeger
authors.affiliation: Klinik fuer Innere Medzin III - Universitätsklinikum Ulm, Germany.
authors.forename: Donald
authors.initials: D
authors.lastname: Bunjes
authors.affiliation: Asklepios Klinik St. Georg - Department of Haematology, Hamburg, Germany.
authors.forename: Bertram
authors.initials: B
authors.lastname: Glass
authors.affiliation: Hopital St. Louis - Dept.of Hematology, Paris, France.
authors.forename: Gerard
authors.initials: G
authors.lastname: Socié
authors.affiliation: Karolinska University Hospital, Department of Hematology, Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Ljungman
authors.affiliation: Center for Clinical Hematology, Queen Elizabeth Hospital, Birmingham, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: Craddock
authors.affiliation: Department of Medicine, Division of Hematology, University of Liège, Belgium.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Baron
authors.affiliation: Department of Hematology, Ospedale San Raffaele, Università degli Studi, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Ciceri
authors.affiliation: Faculté de Médicine Saint-Antoine, Paris, France.
authors.forename: Norbert Claude
authors.initials: NC
authors.lastname: Gorin
authors.affiliation: Dept. of Hematology, Hospital Clinic, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Esteve
authors.affiliation: Klinikum Augsburg, Dept. of Hematology and Oncology, University of Munich, Augsburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schmid
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Giebel
authors.affiliation: Acute Leukemia Working Party, EBMT Paris study office / CEREST-TC, France Department of Haematology, Saint Antoine Hospital, 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: Acute Leukemia Working Party, EBMT Paris study office / CEREST-TC, France Hematology Division, Chaim Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000401:mortality* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors; D055815:Young Adult