Cyclophosphamide priming reduces intestinal damage in man following high dose melphalan chemotherapy.

Pj Selby,J Mundy,Jl Millar,Tj Mcelwain,M Crofts,N Lopes

doi:10.1038/bjc.1987.108

Abstract

A small pre-treatment 'priming' dose of cyclophosphamide will reduce gut damage due to high dose i.v. melphalan in mice and sheep but efforts to demonstrate this effect in man have been hampered by difficulty in the measurement of gut damage. We have evaluated the 51CR EDTA absorption test, a new method for measuring intestinal permeability, as a means of assessing damage due to high dose melphalan. The test was reliable, with a narrow normal range, easy to use and well tolerated. It detected an increase in intestinal permeability after high dose melphalan with a maximum occurring between 9 and 15 days after treatment and subsequently returning to normal. It was shown in 19 patients that a pre-treatment dose of cyclophosphamide was capable of significantly reducing the abnormalities in intestinal permeability which resulted from high dose melphalan.

Highlights

The 5"chromium edetic acid (EDTA) absorption test was introduced as a sensitive, reliable and valid measurement for intestinal permeability in patients with coeliac disease (Bjarnason et al, 1983; Bjarnason & Peters, 1984; Editorial, 1985)
At 9 am IIchromium EDTA prepared to activity of 4 MBq was drunk by the patient in a tasteless, odourless drink followed by 100 ml of water
The percentage of 51chromium EDTA excreted over 24h was calculated from the formula: cpm urine weight of standard cpm standard weight of dose urine volume in mls volume of diluted standard

Summary

Introduction

The 5"chromium edetic acid (EDTA) absorption test was introduced as a sensitive, reliable and valid measurement for intestinal permeability in patients with coeliac disease (Bjarnason et al, 1983; Bjarnason & Peters, 1984; Editorial, 1985). EDTA is an inert molecule which is normally absorbed from the intestine in very small quantities. Damage to the epithelium renders it more permeable allowing increased absorption into the blood stream, probably between cells rather than by an intracellular uptake. The molecule is filtered in the kidneys and excreted in the urine. Increased excretion of 5"chromium EDTA in urine after an oral dose indicates increased intestinal permeability (Selby et al, 1984)

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Discussion

Conclusion