Phase II study of pentostatin in patients with corticosteroid-refractory chronic graft-versus-host disease.
OBJECTIVE
Therapy for patients with chronic graft-versus-host disease (cGVHD) is based on prolonged immunosuppression with corticosteroids. There is no standard therapy for patients whose cGVHD does not resolve with corticosteroid treatment. Pentostatin, a potent inhibitor of adenosine deaminase, has activity in acute GVHD. We examined the toxicity and efficacy of pentostatin in a prospective phase II trial in corticosteroid-refractory cGVHD.


METHODS
Patients of any age were eligible. Patients received pentostatin 4 mg/m2 intravenously every 2 weeks for 12 doses, and continued therapy as long as benefit was documented. Corticosteroid taper was begun after three doses of pentostatin. Responses were graded in real time in the skin, mouth, and liver using objective response criteria.


RESULTS
Fifty-eight heavily pretreated (median, four prior regimens) patients (median age, 33 years) were enrolled. Results are shown as an intent-to-treat analysis. Of the 58 patients, a total of 32 (55%; 95% CI, 42% to 68%) had an objective response, as evaluated by use of a new grading scale. Infection was the most significant toxicity, with 11 grade 3 to 4 infectious events. The survival at 1 and 2 years was 78% (95% CI, 64% to 86%) and 70% (95% CI, 57% to 80%), with cGVHD with/without infection accounting for the majority of deaths.


CONCLUSIONS
Pentostatin has immunosuppressive effects that are currently being explored further for treatment of cGVHD.
Jacobsohn
David A
DA
Robert H. Lurie Comprehensive Cancer Center and Division of Hematology/Oncology/Transplant, Children's Memorial Hospital, Chicago, IL, USA.
Chen
Allen R
AR
Zahurak
Marianna
M
Piantadosi
Steven
S
Anders
Viki
V
Bolaños-Meade
Javier
J
Higman
Meghan
M
Margolis
Jeffrey
J
Kaup
Michele
M
Vogelsang
Georgia B
GB
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance; D006086:Graft vs Host Disease / Q000188:drug therapy*; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007938:Leukemia / Q000150:complications* / Q000628:therapy; D008875:Middle Aged; D015649:Pentostatin / Q000627:therapeutic use*; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D015649:Pentostatin