THE GERMAN CML STUDY, COMPARISON OF BUSULFAN VS HYDROXYUREA VS INTERFERON-ALPHA AND ESTABLISHMENT OF PROGNOSTIC SCORE 1

From July 1983 to January 1991 a total of 622 patients were randomized (585 eligible) to compare the effects of hydroxyurea, interferon alph a (IFN), and busulfan on the duration of chronic phase, and survival. Fur-ther goals included the determination of prognostic parameters. 59 8 CML patients were documented and 575 evaluable. The Ph-status was kn own for 547 patients. 89.4% of the patients were Ph-positive (+). 11 % had additional chromosome aberrations. The median survival of Ph+ pat ients by now is 4.2 years, that of Ph-patients 1.4 years. Ph-negative patients are older, tend to have lower cell counts and, as a group are more ill at diagnosis. A survival difference of about one year is exp ected between busulfan, and hydroxyurea treated patients. Prospectivel y evaluated age, organomegaly related symptoms, Karnofsky index, extra medullary manifestations, number of erythroblasts and percent of circu lating blasts proved to be of prognostic significance. A prognostic sc ore (score 1) was determined which was superior to Sokal's score in th e study population. 164 patients were randomized to receive IFN. In 54 patients (33%) IFN had to be terminated because of adverse effects, t herapy resistance or other reasons. Clinically relevant neutralizing a ntibodies were detected in 9 cases. Most frequent adverse events were flu-like symptoms in 74%, gastrointestinal symptoms in 52%, and neurol ogic-psychiatric symptoms in 30% of patients. Reduction of the Ph-chro mosome was observed in 13% of evaluable patients (10 of 75). In 4 pati ents complete cytogenetic remissions were observed, in three of these ongoing. Cytogenetic responders have a survival advantage. Interferon treated Philadelphia-negative CML patients have no survival disadvanta ge. The study is expected to allow statements as to the advantages or disadvantages of the use of busulfan, hydroxyurea and IFN in the treat ment of CML as well as to the reliability of prognostic markers.