Impact of Complete Kariotypic Remission (CKR) and Sokal Risk on Overall Survival in Chronic Myelogenous Leukemia (CML) Patients: A Monocentric Experience.

Introduction Progressive improvement has been observed in CKR and survival of CML patients (pts) in response to interferon (IFN)a-based regimens, or imatinib. The purpose of this study is the evaluation of:

1. rate of, time to and duration of CKR in accordance to first line therapy employed and Sokal score;

2. impact on overall survival of CKR, and Sokal score, separately considered or combined together.

Patients. 109Ph’+ and 5Ph’−, (BCR-ABL positive), CML pts were treated at diagnosis with allogeneic transplantation (3 pts), hydroxyurea (HU) (19 pts), INFa (51pts, G1), INFa associated with ARA-C (20 pts, G2), imatinib alone (18 pts, G3), or imatinib combined with INFa (3 pts, G4). INFa was employed as second line therapy in 12 pts initially treated with hydroxyurea (G5), while INFa/ARA-C combination or imatinib alone was given to 24 (G6) and 23 (G7) pts with de novo or acquired resistance or intolerance to INFa. Third line therapy, consisting of the combination of imatinib with IFNa, was employed in 11 (G8) pts with no CKR (5 pts) or in complete cytogenetic, but not in molecular remission (6 pts).

Results. 40 of 94 Ph’+ evaluable non-allotransplanted pts obtained one or more (overall 47) CKRs to INFa-based regimens or imatinib. CKR rate, median time to CKR and response duration are shown in table 1. In the analysis according to Sokal score 82/94 pts, with complete prognostic data at diagnosis, were included. The percentage of responders was higher in the low compared to the non-low Sokal risk group (57% vs. 31%). Irrespective of the treatment, median duration value of the first CKR was also better in the former [18+mths(1–64)] than in the latter group [6mths(2–54)] with 16 vs.4 pts still in first or subsequent remission. Overall survival for CKRs was 68+mths(5–275) vs. 52mths(5–270) for CKRs with 35 vs. 6 pts still alive respectively. Overall survival according to Sokal score at diagnosis was 61+ mths(5–275) for low vs 53mths(5–212) for non-low risk patients. The impact on survival of CKR and Sokal risk were then analyzed simultaneously. The median survival of 27 CKRs and 20 not CKRs with low Sokal risk were 61+mths(5–275)and 63 mths(14–270) respectively as compared to 73+mths(11–212) of 11 CKRs and 36mths(5–139) of 24 not CKRs with unfavourable characteristics at diagnosis. The number of patients still alive in these 4 groups were 24/27, 3/20, 8/11, 3/24 respectively at the time when this analysis was performed.

Conclusions. The present data not only confirm the effectiveness of imatinib-over the INFa-based regimens in inducing CKR, but also suggest that response to treatment may be better than Sokal risk in predicting patient survival.