title: Replacement of calcineurin inhibitors with daclizumab in patients with transplantation-associated microangiopathy or renal insufficiency associated with graft-versus-host disease.
abstract: Transplantation-associated microangiopathy (TAM) or renal insufficiency (RI) after allogeneic hematopoietic stem cell transplantation is associated with a high mortality. As calcineurin inhibitors (CI) may contribute to TAM or RI, we evaluated the efficacy of replacing CI by daclizumab in patients with graft-versus-host disease (GVHD). Thirteen patients with GVHD-associated TAM and five patients with RI were treated with daclizumab 1 mg/kg intravenous (i.v.)/week, discontinuation of the CI and continuation of the remaining GVHD treatment. All patients had acute GVHD (steroid-sensitive (n=4), steroid-refractory (n=10)) or chronic GVHD (n=4) and were treated with CI before the start of daclizumab. Nine of 13 patients with TAM treated with daclizumab and discontinuation of CI achieved complete remission of TAM, two had stable disease, and one patient did not respond. Patients receiving daclizumab for RI without TAM showed stabilization (2/5) or improvement (3/5) of renal function. Four of 14 patients with acute GVHD achieved CR, two partial remission, eight patients did not respond and 11/14 died at a median of 39 days after start of the daclizumab. Our data demonstrate that replacement of CI by daclizumab can improve TAM and RI. However, mortality remains high in patients with acute GVHD.
authors.affiliation: Department of Haematology and Oncology, University of Rostock, Rostock, Germany. daniel.wolff@medizin.uni-rostock.de
authors.forename: D
authors.initials: D
authors.lastname: Wolff
authors.forename: S
authors.initials: S
authors.lastname: Wilhelm
authors.forename: J
authors.initials: J
authors.lastname: Hahn
authors.forename: C
authors.initials: C
authors.lastname: Gentilini
authors.forename: I
authors.initials: I
authors.lastname: Hilgendorf
authors.forename: B
authors.initials: B
authors.lastname: Steiner
authors.forename: C
authors.initials: C
authors.lastname: Kahl
authors.forename: C
authors.initials: C
authors.lastname: Junghanss
authors.forename: G
authors.initials: G
authors.lastname: Hartung
authors.forename: J
authors.initials: J
authors.lastname: Casper
authors.forename: L
authors.initials: L
authors.lastname: Uharek
authors.forename: E
authors.initials: E
authors.lastname: Holler
authors.forename: M
authors.initials: M
authors.lastname: Freund
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D065095:Calcineurin Inhibitors; D000077561:Daclizumab; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D019337:Hematologic Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D014184:Transplantation, Homologous; D014652:Vascular Diseases / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D065095:Calcineurin Inhibitors; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000077561:Daclizumab