Predictive Value of Pretreatment BCR-ABLIS Transcript level on Response to Imatinib Therapy in Egyptian Patients with Chronic Phase Chronic Myeloid Leukemia (CPCML)

Background: A wide range of responses of patients with CPCML to IM has been reported. Several factors were proposed to predict response including molecular response at 3 and 6 months. Purpose: To study the impact of pretreatment BCR-ABL transcript level on molecular response to IM, and to assess the value of the milestone ; ≤10% transcript at 3 months on PFS and OS. Patients and Methods:Fifty five adult CP-CML patients receiving daily dose of 400 mg IM were subjected to molecular and cytogenetic analysis at diagnosis and at regular time intervals. Median follow up period was 36 months (15-48). Hematologic, cytogenetic, and molecular responses were rated according to ELN. Results: Two Patient groups were distinguished regarding response to IM therapy. A group of 22/55 patients (40%) having pretreatment BCR-ABLIS level ≤200% and a second patient group 33/55 (60%) having transcript level >200%. The ≤10% milestone was achieved by 15/22 patients (68%) versus 7/33 patients (21%), p=0.04 in favor of the first group. Optimal responders in first group were 14/22 (64%) compared to 13/33 (39%) in second group, p=0.02. Achievement of 10% transcript level significantly correlated with longer PFS. The median BCR-ABLIS transcripts levels in optimal responders at 3, 6 and 18 months was 10%, 2% and 0.1%, respectively compared to 100%, 65% and 10%, in suboptimal/resistant patients p=0.001. Resistance in 11 patients was correlated with identifiable ABL Kinase mutations. Conclusion: The Pretreatment 200% cutoff and the 3 month BCR-ABLIS ≤10% transcript levels proved strong predictors of response to IM and significantly correlated with probability of CCyR, MMR and PFS.