title: Pentostatin in steroid-refractory acute graft-versus-host disease.
abstract: OBJECTIVE
  Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic bone marrow transplantation. In steroid-refractory aGVHD, mortality is very high. Pentostatin, a potent inhibitor of adenosine deaminase, induces lymphocyte apoptosis and may be useful in the treatment of this condition.
  
  
  METHODS
  We have conducted a phase I dose escalation study of pentostatin in patients with steroid-refractory aGVHD. Twenty-three patients were enrolled. Starting dose was 1 mg/m2/d by intravenous injection for 3 days.
  
  
  RESULTS
  The maximum tolerated dose was found to be 1.5 mg/m2/d. Late infections at the 2-mg/m2/d dose level were believed to be dose limiting toxicities. Lymphopenia was universal, but the neutrophil count was generally not affected. Fevers associated with neutropenia were not observed. Otherwise, the drug was well tolerated, with only modest elevations of liver function tests and thrombocytopenia, each being observed in a single patient. Twenty-two patients were assessable for response, including 14 complete responses (63%) and three partial responses (13%). Median survival after therapy for the group was 85 days (range, 5 to 1,258 days).
  
  
  CONCLUSIONS
  The suggested intravenous dose for a phase II study will be 1.5 mg/m2/d for 3 days. Pentostatin has activity in patients with steroid-refractory aGVHD that is worth exploring in future trials.
authors.affiliation: Division of Hematologic Malignancies, Department of Oncology, Johns Hopkins Univeristy, Baltimore, MD 21231, USA.
authors.forename: Javier
authors.initials: J
authors.lastname: Bolaños-Meade
authors.forename: David A
authors.initials: DA
authors.lastname: Jacobsohn
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Margolis
authors.forename: Adam
authors.initials: A
authors.lastname: Ogden
authors.forename: M Guillaume
authors.initials: MG
authors.lastname: Wientjes
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.forename: David M
authors.initials: DM
authors.lastname: Lucas
authors.forename: Viki
authors.initials: V
authors.lastname: Anders
authors.forename: Michele
authors.initials: M
authors.lastname: Phelps
authors.forename: Michael R
authors.initials: MR
authors.lastname: Grever
authors.forename: Georgia B
authors.initials: GB
authors.lastname: Vogelsang
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy*; D019337:Hematologic Neoplasms / Q000628:therapy; D049669:History, 16th Century; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007223:Infant; D007262:Infusions, Intravenous; D008214:Lymphocytes; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D015649:Pentostatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D015649:Pentostatin