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Pentostatin in Steroid-Refractory Acute Graft-Versus-Host Disease

From the Division of Hematologic Malignancies, Department of Oncology, Johns Hopkins University, and The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; the Department of Pediatrics, Northwestern University School of Medicine and the Stem Cell Transplant Program, Children's Memorial Hospital, Chicago, IL; and the Department of Internal Medicine, Ohio State University, Columbus, OH

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 Building 2M89, 1650 Orleans St, Baltimore, MD 21231; e-mail: vogelge{at}jhmi.edu

PURPOSE: 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.

PATIENTS AND 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).

CONCLUSION: 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.

Supported in part by research funding from SuperGen Inc (D.A.J., J.M., J.C.B., M.R.G., and G.B.V.).

Presented in part in the poster session at the 44th Annual Meeting of the American Society of Hematology, Philadelphia, PA, December 6-10, 2002.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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