title: High CD3+ and CD34+ peripheral blood stem cell grafts content is associated with increased risk of graft-versus-host disease without beneficial effect on disease control after reduced-intensity conditioning allogeneic transplantation from matched unrelated donors for acute myeloid leukemia - an analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.
abstract: Inconsistent results have been reported regarding the influence of graft composition on the incidence of graft versus host disease (GVHD), disease control and survival after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplantation (allo-PBSCT). These discrepancies may be at least in part explained by the differences in disease categories, disease status at transplant, donor type and conditioning. The current retrospective EBMT registry study aimed to analyze the impact of CD3+ and CD34+ cells dose on the outcome of RIC allo-PBSCT in patients with acute myelogenous leukemia (AML) in first complete remission, allografted from HLA-matched unrelated donors (10 of 10 match). We included 203 adults. In univariate analysis, patients transplanted with the highest CD3+ and CD34+ doses (above the third quartile cut-off point values, >347 x 10^6/kg and >8.25 x 10^6 /kg, respectively) had an increased incidence of grade III-IV acute (a) GVHD (20% vs. 6%, P = .003 and 18% vs. 7%, P = .02, respectively). There was no association between cellular composition of grafts and transplant-related mortality, AML relapse, incidence of chronic GVHD and survival. Neither engraftment itself nor the kinetics of engraftment were affected by the cell dose. In multivariate analysis, CD3+ and CD34+ doses were the only adverse predicting factors for grade III-IV aGVHD (HR = 3.6; 95%CI: 1.45-9.96, P = .006 and 2.65 (1.07-6.57), P = .04, respectively). These results suggest that careful assessing the CD3+ and CD34+ graft content and tailoring the cell dose infused may help in reducing severe acute GVHD risk without negative impact on the other transplantation outcomes.
authors.affiliation: Department of Bone Marrow Transplantation and Oncohematology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Czerw
authors.affiliation: Clinical Hematology and Cellular Therapy Department, The Acute Leukemia Working Party of the EBMT Office, Hopital Saint-Antoine APHP Paris, France.|INSERM UMRs 938, Paris, France.|Université Pierre et Marie Curie (UPMC, Paris VI), Paris, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Labopin
authors.affiliation: Klinikum Augsburg, University of Munich, Munich, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schmid
authors.affiliation: Department of Hematology, Erasmus University medical center Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Cornelissen
authors.affiliation: CHU Nantes, Department D`Hematologie, Nantes, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Chevallier
authors.affiliation: Unité de Transplantation et de Thérapie Cellulaire, Institut Paoli Calmettes, Marseille, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Blaise
authors.affiliation: University Medical Centre, Department of Haematology, Utrecht, The Netherlands.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kuball
authors.affiliation: CHU Bordeaux, Hôpital Haut-leveque, Pessac, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Vigouroux
authors.affiliation: Hopital A. Michallon, Hématologie Clinique, Pole Cancérologie, Grenoble, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Garban
authors.affiliation: Nouvel Hopital Civil, Strasbourg, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Lioure
authors.affiliation: CHU Lapeyronie, Département d`Hématologie Clinique, Montpellier, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Fegueux
authors.affiliation: Hôpital de Brabois, Centre Hospitalier Universitaire (CHU) de Nancy, Vandoeuvres les Nancy, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Clement
authors.affiliation: University Hospital, Department of Hematology, Linköping, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Sandstedt
authors.affiliation: University Hospital Gasthuisberg, Department of Hematology, Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Maertens
authors.affiliation: CHU Morvan, Brest, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Guillerm
authors.affiliation: CHRU Limoges, Service d`Hématologie Clinique, Limoges, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bordessoule
authors.affiliation: Clinical Hematology and Cellular Therapy Department, The Acute Leukemia Working Party of the EBMT Office, Hopital Saint-Antoine APHP Paris, France.|INSERM UMRs 938, Paris, France.|Université Pierre et Marie Curie (UPMC, Paris VI), Paris, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.affiliation: Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel.|Clinical Hematology and Cellular Therapy Department, The Acute Leukemia Working Party of the EBMT Office, Hopital Saint-Antoine APHP Paris, France.
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000097:blood; D017252:CD3 Complex / Q000097:blood; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D006801:Humans; D007951:Leukemia, Myeloid / Q000097:blood / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D012074:Remission Induction; D012189:Retrospective Studies; D012307:Risk Factors; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; D017252:CD3 Complex
keywords: acute myeloid leukemia (AML); allogenic transplantation; cell dose; reduced-intensity conditioning; stem cell transplantation