title: Long-term follow-up of patients treated with daclizumab for steroid-refractory acute graft-vs-host disease.
abstract: Daclizumab has been shown to have activity in acute GVHD, but appears to be associated with an increased risk of infection. To investigate further the long-term effects of daclizumab, we performed a retrospective review of 57 patients who underwent an allogeneic hematopoietic stem cell transplant from January 1993 through June 2000 and were treated with daclizumab for steroid-refractory acute GVHD. The median number of daclizumab doses given was 5 (range 1-22). GVHD was assessed at baseline, days 15, 29 and 43. By day 43, 54% patients had an improvement in their overall GVHD score, including 76% patients aged < or =18. Opportunistic infections developed in 95% patients. Forty-three patients (75%) died following treatment with daclizumab. The causes of death included active GVHD and infection (79%), active GVHD (5%), chronic GVHD (2%) and relapse (14%). Patients with grade 3-4 GVHD had a significantly shorter median survival than patients with grade 1-2 GVHD (2.0 vs 5.1 months, P=0.001). Daclizumab has no infusion-related toxicity, is active in steroid-refractory GVHD, especially among pediatric patients, but is associated with significant morbidity and mortality due to infectious complications. Careful patient selection and aggressive prophylaxis against viral and fungal infections are recommended.
authors.affiliation: Allogeneic Bone Marrow Transplantation Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. peralesm@mskcc.org
authors.forename: M-A
authors.initials: MA
authors.lastname: Perales
authors.forename: N
authors.initials: N
authors.lastname: Ishill
authors.forename: W A
authors.initials: WA
authors.lastname: Lomazow
authors.forename: D M
authors.initials: DM
authors.lastname: Weinstock
authors.forename: E B
authors.initials: EB
authors.lastname: Papadopoulos
authors.forename: H
authors.initials: H
authors.lastname: Dastigir
authors.forename: M
authors.initials: M
authors.lastname: Chiu
authors.forename: F
authors.initials: F
authors.lastname: Boulad
authors.forename: H R
authors.initials: HR
authors.lastname: Castro-Malaspina
authors.forename: G
authors.initials: G
authors.lastname: Heller
authors.forename: A A
authors.initials: AA
authors.lastname: Jakubowski
authors.forename: R J
authors.initials: RJ
authors.lastname: O'Reilly
authors.forename: T N
authors.initials: TN
authors.lastname: Small
authors.forename: J W
authors.initials: JW
authors.lastname: Young
authors.forename: N A
authors.initials: NA
authors.lastname: Kernan
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D000077561:Daclizumab; D004341:Drug Evaluation; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000150:complications / Q000188:drug therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage*; D007223:Infant; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000139:chemically induced; D012189:Retrospective Studies; D013256:Steroids / Q000494:pharmacology; D014184:Transplantation, Homologous
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D013256:Steroids; D000077561:Daclizumab