Mitigation of late renal and pulmonary injury after hematopoietic stem cell transplantation - PubMed (original) (raw)

Randomized Controlled Trial

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

Eric P Cohen et al. Int J Radiat Oncol Biol Phys. 2012.

Abstract

Purpose: 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).

Methods and materials: 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.

Results: 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).

Conclusions: 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.

Published by Elsevier Inc.

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Conflict of interest statement

Conflicts of Interest Notification: conflicts of interest do not exist

Figures

Fig. 1

Fig. 1

Actuarial patient survival according to use of captopril or placebo. There was better patient survival in the subjects of the captopril group. This survival difference did not, however, attain statistical significance (p = 0.26). Cases censored for survival are shown as vertical bars and the number at risk at 24 month intervals is shown in parentheses.

Fig. 2

Fig. 2

The cumulative incidence of pulmonary-related mortality according to use of captopril or placebo. The occurrence of pulmonary-related mortality was within the two years after the total body irradiation. The placebo group had a higher incidence than the captopril group, but this did not attain statistical significance (p = 0.18). Cases censored are shown as vertical bars and the number at risk at 24 month intervals is shown in parentheses; not shown are placebo cases censored for pulmonary-related mortality at 1.8, 2.2, 2.3 and 2.5 months.

Fig. 3

Fig. 3

The cumulative incidence of bone marrow transplant (BMT) nephropathy and hemolytic uremic syndrome (HUS) according to use of captopril or placebo. The occurrence of BMT nephropathy and HUS was within the first year after the total body irradiation. The placebo group had a higher incidence than the captopril group (p = 0.22). Cases censored are shown as vertical bars and the number at risk at 24 month intervals is shown in parentheses; not shown are placebo cases censored for nephropathy at 1.8, 1.9, 2.2, 2.3 and 2.7 months.

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