title: Targeting interleukin-2 to the bone marrow stroma for therapy of acute myeloid leukemia relapsing after allogeneic hematopoietic stem cell transplantation.
abstract: The antibody-based delivery of IL2 to extracellular targets expressed in the easily accessible tumor-associated vasculature has shown potent antileukemic activity in xenograft and immunocompetent murine models of acute myelogenous leukemia (AML), especially in combination with cytarabine. Here, we report our experience with 4 patients with relapsed AML after allogeneic hematopoietic stem cell transplantation (allo-HSCT), who were treated with the immunocytokine F16-IL2, in combination with low-dose cytarabine. One patient with disseminated extramedullary AML lesions achieved a complete metabolic response identified by PET/CT, which lasted 3 months. Two of 3 patients with bone marrow relapse achieved a blast reduction with transient molecular negativity. One of the 2 patients enjoyed a short complete remission before AML relapse occurred 2 months after the first infusion of F16-IL2. In line with a site-directed delivery of the cytokine, F16-IL2 led to an extensive infiltration of immune effector cells in the bone marrow. Grade 2 fevers were the only nonhematologic side effects in 2 patients. Grade 3 cytokine-release syndrome developed in the other 2 patients but was manageable in both cases with glucocorticoids. The concept of specifically targeting IL2 to the leukemia-associated stroma deserves further evaluation in clinical trials, especially in patients who relapse after allo-HSCT.
authors: Department of Medicine A, Hematology and Oncology, University Hospital Muenster, Muenster, Germany.
authors: Christoph
authors: C
authors: Schliemann
authors: Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
authors: Katrin L
authors: KL
authors: Gutbrodt
authors: Department of Medicine A, Hematology and Oncology, University Hospital Muenster, Muenster, Germany.
authors: Andrea
authors: A
authors: Kerkhoff
authors: Department of Medicine A, Hematology and Oncology, University Hospital Muenster, Muenster, Germany.
authors: Michele
authors: M
authors: Pohlen
authors: Department of Medicine A, Hematology and Oncology, University Hospital Muenster, Muenster, Germany.
authors: Stefanie
authors: S
authors: Wiebe
authors: Department of Medicine A, Hematology and Oncology, University Hospital Muenster, Muenster, Germany.
authors: Gerda
authors: G
authors: Silling
authors: Department of Medicine A, Hematology and Oncology, University Hospital Muenster, Muenster, Germany.
authors: Linus
authors: L
authors: Angenendt
authors: Department of Medicine A, Hematology and Oncology, University Hospital Muenster, Muenster, Germany.
authors: Torsten
authors: T
authors: Kessler
authors: Department of Medicine A, Hematology and Oncology, University Hospital Muenster, Muenster, Germany.
authors: Rolf M
authors: RM
authors: Mesters
authors: Philogen SpA, Siena, Italy.
authors: Leonardo
authors: L
authors: Giovannoni
authors: Department of Nuclear Medicine, University Hospital Muenster, Muenster, Germany.
authors: Michael
authors: M
authors: Schäfers
authors: Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Muenster, Germany.
authors: Bianca
authors: B
authors: Altvater
authors: Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Muenster, Germany.
authors: Claudia
authors: C
authors: Rossig
authors: Gerhard-Domagk-Institute for Pathology, University Hospital Muenster, Muenster, Germany.
authors: Inga
authors: I
authors: Grünewald
authors: Gerhard-Domagk-Institute for Pathology, University Hospital Muenster, Muenster, Germany.
authors: Eva
authors: E
authors: Wardelmann
authors: Gerhard-Domagk-Institute for Pathology, University Hospital Muenster, Muenster, Germany. Institute of Pathology, General Hospital Fulda, Fulda, Germany.
authors: Gabriele
authors: G
authors: Köhler
authors: Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
authors: Dario
authors: D
authors: Neri
authors: Department of Medicine A, Hematology and Oncology, University Hospital Muenster, Muenster, Germany.
authors: Matthias
authors: M
authors: Stelljes
authors: Department of Medicine A, Hematology and Oncology, University Hospital Muenster, Muenster, Germany. berdel@uni-muenster.de.
authors: Wolfgang E
authors: WE
authors: Berdel
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001853:Bone Marrow / Q000276:immunology*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D012008:Recurrence; D019063:Tenascin / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D019063:Tenascin