title: Treatment of acute myeloid leukemia or myelodysplastic syndrome relapse after allogeneic stem cell transplantation with azacitidine and donor lymphocyte infusions--a retrospective multicenter analysis from the German Cooperative Transplant Study Group.
abstract: To expand the current knowledge about azacitidine (Aza) and donor lymphocyte infusions (DLI) as salvage therapy for relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to identify predictors for response and survival, we retrospectively analyzed data of 154 patients with acute myeloid leukemia (AML, n = 124), myelodysplastic (MDS, n = 28), or myeloproliferative syndrome (n = 2). All patients received a median number of 4 courses of Aza (range, 4 to 14) and DLI were administered to 105 patients (68%; median number of DLI, 2; range, 1 to 7). Complete and partial remission rates were 27% and 6%, respectively, resulting in an overall response rate of 33%. Multivariate analysis identified molecular-only relapse (hazard ratio [HR], 9.4; 95% confidence interval [CI], 2.0 to 43.5; P = .004) and diagnosis of MDS (HR, 4.1; 95% CI, 1.4 to 12.2; P = .011) as predictors for complete remission. Overall survival (OS) at 2 years was 29% ± 4%. Molecular-only relapse (HR, .14; 95% CI, .03 to .59; P = .007), diagnosis of MDS (HR, .33; 95% CI, .16 to .67; P = .002), and bone marrow blasts <13% (HR, .54; 95% CI, .32 to .91; P = .021) were associated with better OS. Accordingly, 2-year OS rate was higher in MDS patients (66% ± 10%, P = .001) and correlated with disease burden in patients with AML. In summary, Aza and DLI is an effective and well-tolerated treatment option for patients with relapse after allo-HSCT, in particular those with MDS or AML and low disease burden. The latter finding emphasizes the importance of stringent disease monitoring and early intervention.
authors.affiliation: Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany. Electronic address: thomas.schroeder@med.uni-duesseldorf.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schroeder
authors.affiliation: Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Rachlis
authors.affiliation: Department of Medicine II, University Hospital, Frankfurt, Germany.
authors.forename: Gesine
authors.initials: G
authors.lastname: Bug
authors.affiliation: Department of Medicine A, Hematology and Oncology, University of Muenster, Muenster, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Stelljes
authors.affiliation: Universitätsmedizin Mannheim, Med. Klinik III, Mannheim, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Klein
authors.affiliation: Clinic for Bone Marrow Transplants, University Hospital Essen, Essen, Germany.
authors.forename: Nina Kristin
authors.initials: NK
authors.lastname: Steckel
authors.affiliation: University Hospital Bonn, Med. Klinik III, Bonn, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Wolf
authors.affiliation: Department of Medicine III, Karlsruhe Hospital, Karlsruhe, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Ringhoffer
authors.affiliation: Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany.
authors.forename: Akos
authors.initials: A
authors.lastname: Czibere
authors.affiliation: Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Nachtkamp
authors.affiliation: Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany.
authors.forename: Ariane
authors.initials: A
authors.lastname: Dienst
authors.affiliation: Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Kondakci
authors.affiliation: Hannover Medical School, Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Stadler
authors.affiliation: University Hospital Carl Gustav Carus, Medical Clinic and Policlinic I, Dresden, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Platzbecker
authors.affiliation: Charité Campus Benjamin Franklin, Medical Clinic Hematology, Oncology and Tumorimmunology, Berlin, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Uharek
authors.affiliation: Department of Medicine V, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Luft
authors.affiliation: Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Fenk
authors.affiliation: Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Germing
authors.affiliation: University Hospital Carl Gustav Carus, Medical Clinic and Policlinic I, Dresden, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
authors.affiliation: University Hospital Hamburg-Eppendorf, Clinic for Stem Cell Transplantation, Hamburg, Germany.
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
authors.affiliation: Clinic for Bone Marrow Transplants, University Hospital Essen, Essen, Germany.
authors.forename: Dietrich W
authors.initials: DW
authors.lastname: Beelen
authors.affiliation: Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
authors.affiliation: Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Kobbe
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D001374:Azacitidine / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000401:mortality / Q000628:therapy; D011446:Prospective Studies; D012008:Recurrence; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine
keywords: Acute myeloid leukemia; Azacitidine; Donor lymphocyte infusions; Myelodysplastic syndromes; Relapse; Transplantation