Pentostatin in steroid-refractory acute graft-versus-host disease.
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.
Bolaños-Meade
Javier
J
Division of Hematologic Malignancies, Department of Oncology, Johns Hopkins Univeristy, Baltimore, MD 21231, USA.
Jacobsohn
David A
DA
Margolis
Jeffrey
J
Ogden
Adam
A
Wientjes
M Guillaume
MG
Byrd
John C
JC
Lucas
David M
DM
Anders
Viki
V
Phelps
Michele
M
Grever
Michael R
MR
Vogelsang
Georgia B
GB
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
D007166:Immunosuppressive Agents; D015649:Pentostatin