title: Azacitidine and donor lymphocyte infusions as first salvage therapy for relapse of AML or MDS after allogeneic stem cell transplantation.
abstract: The combination of azacitidine and donor lymphocyte infusions (DLI) as first salvage therapy for relapse after allogeneic transplantation (allo-HSCT) was studied in 30 patients with acute myeloid leukemia (AML; n=28) or myelodysplastic syndromes (MDS; n=2) within a prospective single-arm multicenter phase-II trial. Treatment schedule contained up to eight cycles azacitidine (100 mg/m(2)/day, days 1-5, every 28 days) followed by DLI (from 1-5 × 10(6) to 1-5 × 10(8) CD3(+)cells/kg) after every second azacitidine cycle. A median of three courses azacitidine (range 1-8) were administered, and 22 patients (73%) received DLI. Overall response rate was 30%, including seven complete remissions (CRs, 23%) and two partial remissions (7%). Five patients remain in CR for a median of 777 days (range 461-888). Patients with MDS or AML with myelodysplasia-related changes were more likely to respond (P=0.011), and a lower blast count (P=0.039) as well as high-risk cytogenetics (P=0.035) correlated with the likelihood to achieve CR. Incidence of acute and chronic graft-versus-host disease was 37% and 17%, respectively. Neutropenia and thrombocytopenia grade III/IV occurred during 65% and 63% of treatment cycles, while infections were the most common grade III/IV non-hematological toxicity. Azacitidine and DLI as salvage therapy is safe, induces long-term remissions and may become an alternative for patients with AML or MDS relapsing after allo-HSCT.
authors: Medical Faculty, Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany. thomas.schroeder@med.uni-duesseldorf.de
authors: T
authors: T
authors: Schroeder
authors: A
authors: A
authors: Czibere
authors: U
authors: U
authors: Platzbecker
authors: G
authors: G
authors: Bug
authors: L
authors: L
authors: Uharek
authors: T
authors: T
authors: Luft
authors: A
authors: A
authors: Giagounidis
authors: F
authors: F
authors: Zohren
authors: I
authors: I
authors: Bruns
authors: C
authors: C
authors: Wolschke
authors: K
authors: K
authors: Rieger
authors: R
authors: R
authors: Fenk
authors: U
authors: U
authors: Germing
authors: R
authors: R
authors: Haas
authors: N
authors: N
authors: Kröger
authors: G
authors: G
authors: Kobbe
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001374:Azacitidine / Q000627:therapeutic use*; D017690:Cell Transplantation; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D008214:Lymphocytes / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D012008:Recurrence; D016879:Salvage Therapy; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous
chemical_list: D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine