Comparison of the antileukemic activity in vitro of dexamethasone and prednisolone in childhood acute lymphoblastic leukemia

✍ Scribed by Kaspers, G. J. L.; Veerman, A. J. P.; Popp-Snijders, C.; Lomecky, M.; Van Zantwijk, C. H.; Swinkels, L.M.J.W.; Van Wering, E. R.; Pieters, R.

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 738 KB
• Volume: 27
• Category: Article
• ISSN: 0098-1532
• DOI: 10.1002/(sici)1096-911x(199608)27:2<114::aid-mpo8>3.0.co;2-i

✦ Synopsis

It is generally assumed that prednisolone (PRD) and dexamethasone (DXM) have equal glucocorticoid activity if PRD is given at sev- enfold higher doses. Resultsofclinical studiesof childhood acute lymphoblastic leukemia (ALL) suggested that DXM is more potent relative to PRD than assumed. The purpose of this study was todeterminethe relativeantileukemicactiv- ity of PRD phosphate and DXM phosphate in 133 untreated childhood ALL samples in vitro, using the 3 -(4,5 -d i methyl th i azol-2 -y 1)-2,5 -diphenyltetrazolium-bromide (MTT) assay. There was a marked variation in antileukemic activity of both agents among the patient samples. The median LC50 (drug concentration lethal to 50%, of the ALL cells) for PRD phosphate was 3.50 pM, for DXM phosphate0.20 pM. The individually calculated ratios of the LC50 values for PRD and DXM phosphate showed a large range from 0.7 to >500, with a median of 16.2. This 16-fold difference could not be explained by differences between these glucocorticoids in stability, hydrolysis into unesterified drug, adhesion to the wall of the microculture plates, or protein binding. ALL cells were cross-resistant to PRD and DXM phosphate (correlation coefficient = 0.85, P < 0.000001).

We conclude that the in vitro antileukemic activity of DXM phosphate is median 16-fold higher than that of PRD phosphate, which contrasts to the generally assumed factor of 7. Based on the higher potency of DXM, and its more favorable pharmacokinetics as reported in the literature, DXM may be preferred to PRD as the glucocorticoid in the treatment of ALL.