Pentostatin in steroid-refractory acute graft-versus-host disease

Javier Bolaños-Meade, David A. Jacobsohn, Jeffrey Margolis, Adam Ogden, M. Guillaume Wientjes, John C. Byrd, David M. Lucas, Viki Anders, Michele Phelps, Michael R. Grever, Georgia B. Vogelsang

Research output: Contribution to journalArticlepeer-review

Abstract

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/m 2/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/m 2/d for 3 days. Pentostatin has activity in patients with steroid-refractory aGVHD that is worth exploring in future trials.

Original languageEnglish (US)
Pages (from-to)2661-2668
Number of pages8
JournalJournal of Clinical Oncology
Volume23
Issue number12
DOIs
StatePublished - Apr 20 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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