Phase I study of urate oxidase in the reduction of acute graft-versus-host disease after myeloablative allogeneic stem cell transplantation.

Abstract

Graft-versus-host disease (GVHD) is a donor T cell driven response against host tissue that can complicate allogeneic hematopoietic stem cell transplantation (HSCT). During acute GVHD, endogenous adjuvants such as uric acid are released by damaged host tissue, activating alloreactive donor T cells. A phase I study was conducted at the Massachusetts General Hospital between 2007 and 2010 to test the hypothesis that reduction of uric acid levels during allogeneic HSCT can modulate the development of acute GVHD. Twenty-one patients with hematologic malignancies in complete remission undergoing myeloablative peripheral blood HSCT received recombinant urate oxidase at .20 mg/kg for 5 consecutive days during conditioning. Results were compared with all patients who underwent allogeneic HSCT at our institution during the same time period who met the same inclusion and exclusion criteria but were not enrolled in the study. The only major adverse event was a case of hemolytic anemia in a patient who had glucose-6-phosphate dehydrogenase deficiency. Primary outcome was the cumulative incidence of grades II to IV acute GVHD, which was significantly decreased in the treatment group in the intention-to-treat analysis (57% [12/21] versus 24% [5/21], P = .036) and in the per-protocol analysis (P = .017). Patients who developed acute GVHD had a higher level of serum uric acid during the pretransplantation period compared with those who did not (P < .001). There was no difference in disease-free or overall survival. Our study suggests that urate oxidase can be safely administered during myeloablative conditioning and may reduce the incidence of acute GVHD.

• Authors: Albert C Yeh, Andrew M Brunner, Thomas R Spitzer, Yi-Bin Chen, Erin Coughlin, Steven McAfee, Karen Ballen, Eyal Attar, Martin Caron, Frederic I Preffer, Beow Y Yeap, Bimalangshu R Dey
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 20 Issue 5 Pg. 730-4 (May 2014) ISSN: 1523-6536 [Electronic] United States
• PMID: 24530972 (Publication Type: Clinical Trial, Phase I, Journal Article)
• Copyright: Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Myeloablative Agonists
• Recombinant Proteins
• Uric Acid
• Urate Oxidase

Topics

• Acute Disease
• Adult
• Drug Administration Schedule
• Female
• Graft vs Host Disease (blood, pathology, prevention & control)
• Hematologic Neoplasms (blood, mortality, pathology, therapy)
• Hematopoietic Stem Cell Transplantation
• Humans
• Lymphocyte Activation (drug effects)
• Male
• Middle Aged
• Myeloablative Agonists (therapeutic use)
• Recombinant Proteins (therapeutic use)
• Remission Induction
• Survival Analysis
• T-Lymphocytes (drug effects, immunology, pathology)
• Transplantation Conditioning
• Transplantation, Homologous
• Urate Oxidase (therapeutic use)
• Uric Acid (blood)