Chronic-phase chronic myeloid leukemia: Incidence of BCR/ABL transcript and its correlation with presenting features, response to treatment, and survival

Abstract

Introduction: Chronic myeloid leukemia (CML) is characterized by Philadelphia chromosome resulting in the fusion between the BCR gene, located on chromosome 22, and the ABL gene on chromosome 9. The prognostic significance of BCR-ABL transcript variants in CML is controversial. The aim of the current study was to evaluate the clinico-hematological presentation and evolution of the disease, response to treatment and survival according to transcript type in chronic phase CML patients. Results: The median age of our population was 50 years with a slight female predominance (sex-ratio 0.78). Sixty percent had the b3a2 transcript and 34% had the b2a2 type. Patients with the co-expression of these two transcripts (4.5%) and those with e19a2 were excluded from the analysis. Patients with b3a2 subtype were associated significantly with thrombocytosis (p = 0.006) and higher Sokal score (p = 0.038) compared to those with b2a2 transcript. The two isolated transcripts were not significantly associated with gender, age group, blast cell percentage or the identified ranges of spleen size. Complete cytogenetic response at 12 months for b3a2 patients and b2a2 patients was 78.6% and 21.4% respectively. This difference was statistically significant (p = 0.001, HR = 9.5, 95% CI 6.5–13.7). Patients with b3a2 transcript had a higher rate of optimal molecular response at 3 months (p = 0.04, HR = 4.2, 95% CI 1–17.3) and major molecular response at 12 months (p = 0.004, HR = 4.9, 95%CI 1.5–15.1). At the date of last follow-up, most patients achieving deep molecular response (MR4 or deeper) belonged to b3a2 group (79%) (p = 0.003, HR = 5.2, 95% CI 1.6–16.4). We did not find a significant difference in OS and EFS between the two groups. Conclusion: Our study concluded that b2a2 transcript is a prognostic factor in cytogenetic and molecular response but further studies are needed to complete this aspect.

Keywords

• Myeloproliferative disorder
• Chronic phase
• Philadelphia chromosome
• BCR-ABL transcript
• Imatinib mesylate