Mitigation of late renal and pulmonary injury after hematopoietic stem cell transplantation.

To update the results of a clinical trial that assessed whether the angiotensin-converting enzyme inhibitor captopril was effective in mitigating chronic renal failure and pulmonary-related mortality in subjects undergoing total body irradiation (TBI) in preparation for hematopoietic stem cell transplantation (HSCT).
Updated records of the 55 subjects who were enrolled in this randomized controlled trial were analyzed. Twenty-eight patients received captopril, and 27 patients received placebo. Definitions of TBI-HSCT-related chronic renal failure (and relapse) were the same as those in the 2007 analysis. Pulmonary-related mortality was based on clinical or autopsy findings of pulmonary failure or infection as the primary cause of death. Follow-up data for overall and pulmonary-related mortality were supplemented by use of the National Death Index.
The risk of TBI-HSCT-related chronic renal failure was lower in the captopril group (11% at 4 years) than in the placebo group (17% at 4 years), but this was not statistically significant (p > 0.2). Analysis of mortality was greatly extended by use of the National Death Index, and no patients were lost to follow-up for reasons other than death prior to 67 months. Patient survival was higher in the captopril group than in the placebo group, but this was not statistically significant (p > 0.2). The improvement in survival was influenced more by a decrease in pulmonary mortality (11% risk at 4 years in the captopril group vs. 26% in the placebo group, p = 0.15) than by a decrease in chronic renal failure. There was no adverse effect on relapse risk (p = 0.4).
Captopril therapy produces no detectable adverse effects when given after TBI. Captopril therapy reduces overall and pulmonary-related mortality after radiation-based HSCT, and there is a trend toward mitigation of chronic renal failure.
AuthorsEric P Cohen, Manpreet Bedi, Amy A Irving, Elizabeth Jacobs, Rade Tomic, John Klein, Colleen A Lawton, John E Moulder
JournalInternational journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 83 Issue 1 Pg. 292-6 (May 1 2012) ISSN: 1879-355X [Electronic] United States
PMID22104363 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightPublished by Elsevier Inc.
Chemical References
  • Angiotensin-Converting Enzyme Inhibitors
  • Radiation-Protective Agents
  • Captopril
  • Adult
  • Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
  • Captopril (therapeutic use)
  • Child
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Kidney Failure, Chronic (etiology, mortality, prevention & control)
  • Lung Injury (etiology, mortality, prevention & control)
  • Male
  • Prospective Studies
  • Radiation Injuries (prevention & control)
  • Radiation-Protective Agents (therapeutic use)
  • Transplantation Conditioning (adverse effects, methods)
  • Whole-Body Irradiation (adverse effects, methods)

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