UK MEDICAL-RESEARCH-COUNCIL RANDOMIZED, MULTICENTER TRIAL OF INTERFERON-ALPHA-N1 FOR CHRONIC MYELOID-LEUKEMIA - IMPROVED SURVIVAL IRRESPECTIVE OF CYTOGENETIC RESPONSE

Interferon-alpha may be better than cytotoxic drugs in the long-term m anagement of patients with chronic myeloid leukaemia (CML) in chronic phase. To test this possibility 587 patients with CML in chronic phase were randomly allocated to receive lymphoblastoid cell-line interfero n-alpha n1 (IFN-alpha, n=293) or chemotherapy with busulphan or hydrox yurea (no IFN-alpha, n=294) as maintenance after initial induction tre atment with cytotoxic drugs. There was a significant survival benefit for patients in the IFN-alpha arm when analysed on the basis of intent ion to treat (2p=0.0009). The median survival for those allocated IFN- alpha was 61 months and no IFN-alpha was 41 months. Out of 269 patient s with Philadelphia-positive CML in the IFN-alpha arm with at least 6 months follow-up, 211 were evaluable for haematological response: 145 (68%) achieved good responses (A+ or A type), 37 (18%) had partial res ponses (B type) and 29 (14%) had poor responses (C type). Patients wit h types A and B responses had a better survival than those in the no I FN-alpha arm; patients with type C responses had survival equivalent t o the no IFN-alpha arm. Of these 269 patients, 26 of whom had not star ted IFN-alpha, 59 (22%) achieved a significant degree of cytogenetic r esponse but 210 (78%) did not have response. Cytogenetic responders su rvived significantly longer than non-responders and even non-responder s survived longer than patients in the no IFN-alpha arm. Since cytogen etic nonresponders had worse than average prognostic features, they ma y also benefit from IFN-alpha therapy. We conclude that treatment with IFN-alpha prolongs the survival of patients with CML; benefits of IFN -alpha are not confined to cytogenetic responders but may extend to mo st, if not all patients receiving IFN-alpha treatment; and cytogenetic response to IFN-alpha treatment identifies patients with a relatively good prognosis.