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Phase II Study of Pentostatin in Patients With Corticosteroid-Refractory Chronic Graft-Versus-Host Disease

David A. Jacobsohn, Allen R. Chen, Marianna Zahurak, Steven Piantadosi, Viki Anders, Javier Bolaños-Meade, Meghan Higman, Jeffrey Margolis, Michele Kaup, Georgia B. Vogelsang

From the Robert H. Lurie Comprehensive Cancer Center and Division of Hematology/Oncology/Transplant, Children's Memorial Hospital, Chicago, IL; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD; and the Rose Cancer Center, William Beaumont Hospital, Royal Oak, MI

Address reprint requests to Georgia B. Vogelsang, MD, Division of Hematologic Malignancies, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Bunting-Blaustein Cancer Research Bldg 2M89, 1650 Orleans St, Baltimore, MD 21231; e-mail: vogelge{at}jhmi.edu

Purpose 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.

Patients and 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.

Conclusion Pentostatin has immunosuppressive effects that are currently being explored further for treatment of cGVHD.

Presented in part at the American Society of Hematology Meeting, Atlanta, GA, December 10-13, 2005.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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