Stage, percentage of basophils at diagnosis, hematologic response within six months, cytogenetic response in the first year: the main prognostic variables affecting outcome in patients with chronic myeloid leukemia in chronic phase treated with interferon-alpha. Results of the CML89 trial of the Spanish Collaborative Group on interferon-alpha 2a and CML

Background and Objectives. Interferon-alpha (IFN) Is increasingly being use d as the drug of choice in chronic myeloid leukemia patients. The main obje ctives of the study were to study the influence of the classic prognostic v ariables and response to IFN, and to assess the influence of this response on the course of the disease and survival. Design and Methods. Single arm, prospective, multicenter study, without a c entral group. Only Ph1-positive CML patients were included. The treatment s cheme was biphasic: the patients first received standard chemotherapy and t hereafter IFN-alpha 2a was used as monotherapy, with a target dose of 9 MU/ d/s.c. Results. Twenty-one centers in Spain enrolled 132 patients (72 men, 60 wome n). the median dose of IFN given was 5.8 MU/d, and the median treatment dur ation was 431 days (range: 18-2,597). Seventy-two percent of patients obtai ned a hematologic response in the first six months of IM treatment. Genetic response was obtained in 47% of the patients, and the response was major o r complete in 27% and 19%, respectively. The median time to obtain this res ponse was 7, 9, and 18 months for minimal, partial and complete genetic res ponse, respectively. Multivariant analysis showed that only a higher percen tage of basophils at diagnosis was associated with a worse hematologic resp onse at six months (p=0.001) (OR: 1.23) and with a worse cytogenetic respon se in the first year of IFN therapy (p=0.018) (OR: 1.4). Over an observatio n period of 8 years, 35.6% of the patients died, and 85 (64.4%) remained al ive. With a median follow-up of 42 months (3.7-98), the 6-year projected pr obabilities of survival and transformation-free survival were 0.61+/-0.07 v s. 0.54+/-0.07, respectively. Patients with Kantarjian's stage 3 disease or in a high-risk Sokal group had lower probabilities of survival, but these systems did not adequately discriminate In our series. Obtaining a complete hematologic response in the first six months of IFN therapy was favorable In terms of overall survival (p=0.05; HR=0.33). Cox's analysis demonstrated that obtaining a cytogenetic response in the first year was independently associated with better overall survival (p=0.04; HR=0.19) and better transf ormation-free survival (p=0.0035; HR=0.11). Interpretation and Conclusions. Nearly half of the patients obtained some d egree of Philadelphia suppression, which was major In 27%,and complete in 1 9%. A higher percentage of basophils at diagnosis was the only variable ass ociated with a lower probability of cytogenetic response. Obtaining a cytog enetic response during the first year of IFN treatment was a favorable and Independent variable In terms of survival and transformation-free survival. Obtaining a major cytogenetic response during this period decreased the ri sk of transformation twenty times. Our results suggest that the effect of I FN on survival Is independent of the classic prognostic variables. (C) 1999 , Ferrata Storti Foundation.