Hydroxyurea versus busulphan for chronic myeloid leukaemia: an individual patient data meta-analysis of three randomized trials

Although interferon alpha (IFN) has been shown to prolong survival in chron ic myeloid leukaemia (CML), it cannot be used in all patients. Reliable evi dence on the relative benefits of busulphan and hydroxyurea is of value in treating those patients who will not receive interferon. Data for each indi vidual patient was sought from trials which randomized patients with CML to hydroxyurea vs. busulphan. Intention-to-treat stratified log rank survival analyses were performed, reporting two-sided P-values. Data were collected on 812 patients in the three trials identified. In the group of 690 patien ts with confirmed Philadelphia chromosome (Ph)-positive CML, survival at 4 years was 45.1% with busulphan and 53.6% with hydroxyurea, an absolute bene fit of 8.5% (9.5% confidence interval 0.1-16.9; logrank P = 0.01 over 4 yea rs). There seemed to be no further benefit for hydroxyurea in later years, but there was no apparent delayed adverse effect either. The difference bet ween hydroxyurea and busulphan was not statistically significantly differen t from the overall result in any subgroup. Survival of patients with Ph-pos itive CML is better with hydroxyurea treatment than with busulphan.