Four RCTs (1,673 patients) were included. No trials were blinded, and the methods of randomisation and allocation concealment were unclear in all trials. Median follow up periods ranged from 17 to 47 months.
After one year following high-dose imatinib, both the complete cytogenetic response (RR 1.17, 95% CI 1.08 to 1.26; four RCTs; Ι²= 33%) and the major molecular response (RR 1.26, 95% CI 1.12 to 1.42; four RCTs; Ι²= 0%) were statistically significantly improved. A sensitivity analysis for major molecular response, which excluded a study with fewer high-risk patients, yielded similar results. Statistically significant benefit from high dose treatment was also evident at the three, six, 18 and 24 month time points for major molecular response, and at six months for complete cytogenetic response.
There were no statistically significant differences between groups in all-cause mortality or disease progression (both three RCTs).
Adverse events resulting in discontinuation of treatment were significantly more frequent with high-dose imatinib (RR 1.98, 95% CI 1.20 to 3.26; three RCTs; Ι²=0%), as were Grade III/IV neutropenia and thrombocytopenia. There were no significant differences between groups for incidence of anaemia and Grade III/IV non-haematologic adverse events (except for diarrhoea).