Lower incidence of meningeal leukemia when prednisone is replaced by dexamethasone in the treatment of acute lymphocytic leukemia

Abstract

In 1971, Cancer and Leukemia Group B (CALGB) mounted a study of acute lymphocytic leukemia (ALL) that compared the effects of the two steroid hormones dexamethasone and prednisone. Six-hundred-forty-six children and adolescents with ALL were randomized to receive either prednisone or dexamethasone as part of their remission induction therapy. The 493 evaluable patients who achieved complete remission received the same steroid as pulses throughout remission. Specific central nervous system (CNS) therapy was randomized to either six injections of intrathecal methotrexate (IT MTX) alone or to six injections of IT MTX with cranial radiation (2,400 cGy). Both cranial radiation and dexamethasone offered increased protection against CNS relapse as the first site of failure over IT MTX alone. There were 30 CNS relapses among 238 patients (12.6%) receiving cranial radiation plus IT MTX, whereas there were 70 CNS relapses among 225 (P less than 0.001) (22.5%) in those who received IT MTX alone. Similarly, there were 33 CNS relapses among 231 (14.3%) children treated with dexamethasone, whereas there were 67 CNS relapses among 262 (25.6%) treated with prednisone (P = 0.017). Both steroids appeared equal in protecting the bone marrow. Recent national studies have shown significant improvements in preventing CNS relapse over the results in the present report. However, this finding warrants further investigation and, with further documentation, could lead to the substitution of prednisone by dexamethasone to aid further in preventing CNS relapse. This may be particularly important in patients at higher risk for CNS relapse.

Dexamethasone versus prednisone for induction therapy in childhood acute lymphoblastic leukemia: a systematic review and meta-analysis

“…Of these, eight studies satisfied eligibility criteria and were included in the metaanalysis. [6][7][8][9][14][15][16]22 The reviewers had perfect agreement on articles for inclusion, with a k statistic of 1.0. The reasons for excluding 15 articles are shown in Figure 1.…”

“…7,9 Blinding status was not reported by any study. Withdrawal information could be retrieved from four of the eight, [6][7][8]22 and intention-to-treat analysis was reported for three trials 6,8,14,16 (Supplementary Data B).…”

“…Qualitatively, there appeared to be superiority for DEX in studies with PRED/DEX dose ratios o7 and superiority for PRED in studies using ratios X7 (both non-significant; Table 2 and Supplementary Data C). No significant difference between DEX and PRED was identified in terms of overall mortality (three studies) 6,7,22 or testicular relapse (two studies) 6,8 ( Table 2). Only one study provided data regarding combined relapse.…”

Dexamethasone compared to prednisolone for adults with acute lymphoblastic leukemia or lymphoblastic lymphoma: final results of the ALL-4 randomized, phase III trial of the EORTC Leukemia Group

“…Branimir Jaksic, 8 Walter Feremans, 9 Dominique Bron, 10 Harm Sinnige, 11 Martin Mistrik, 12 Gerard Vreugdenhil, 13 Robrecht De Bock, 14 Damir Nemet, 1 Caroline Gilotay, 2 Sergio Amadori, 15 …”

Prednisolone concentrations in cerebrospinal fluid after different prednisolone prodrugs.

“…Recently, plasma and CSF concentration-time profiles after an intravenous bolus dose of prednisolone phosphate were measured in three rhesus monkeys by Balis et al (1987). The CSF concentrations of prednisolone were very low and it was suggested that this might be one reason for the poor efficacy of prednisolone in the treatment of central nervous system leukemia in man (Jones et al, 1975(Jones et al, , 1984. The purpose of the present study was to investigate the relationship between prednisolone concentrations in plasma and CSF in humans after intravenous administration of equimolar doses of two prednisolone prodrugs, prednisolone phosphate and prednisolone phthalate.…”