Prognostic significance of a normal karyotype in adult patients with BCR-ABL1-positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era

OBJECTIVE:

The occurrence of cryptic Philadelphia (Ph) chromosome translocation is rare in BCR-ABL1-positive acute lymphoblastic leukemia (BCR-ABL1⁺ ALL) and is of unknown significance in the tyrosine kinase inhibitor (TKI) era.

METHODS:

We retrospectively studied a series of adult patients receiving TKI-based therapy to evaluate the prognostic impact of the normal karyotype (NK) (n=22) in BCR-ABL1⁺ ALL by comparison with the isolated Ph⁺ karyotype (n=54).

RESULTS:

There were no statistically significant differences in clinical characteristics and complete remission rate between the two groups. Compared with the isolated Ph⁺ group, the NK/BCR-ABL1⁺ group had a higher relapse rate (55.0% versus 29.4%, p=0.044). Overall survival (OS) and disease-free survival (DFS) were significantly shorter in the NK/BCR-ABL1⁺ group than in the isolated Ph⁺ group [median OS: 24.5 versus 48.6 (months), p=0.013; median DFS: 11.0 (months) versus undefined, p=0.008]. The five-year OS and DFS for patients with NK/BCR-ABL1⁺ were 19.2% and 14.5%, respectively; those for patients with isolated Ph⁺ were 49.5% and 55.7%, respectively. Thirty-four (44.7%) patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in this study. Among the patients who received allo-HSCT, the median OS and DFS in the NK/BCR-ABL⁺ group (n=9) were 35.5 and 27.5 months, respectively, while those in the isolated Ph⁺ group (n=25) were undefined. There was a trend of significant statistical difference in the OS between the two subgroups (p=0.066), but no significant difference in the DFS. Multivariate analysis revealed that NK was independently associated with worse OS and DFS in BCR-ABL1⁺ ALL patients [Hazard ratio (HR) 2.256 (95% confidence interval (CI), 1.005-5.066), p=0.049; HR 2.711 (95% CI, 1.319-5.573), p=0.007].

CONCLUSION:

Our results suggest that the sub-classification of an NK could be applied in the prognostic assessments of BCR-ABL1⁺ ALL. In addition, allo-HSCT should be actively performed to improve prognosis in these patients.

Acute Lymphoblastic Leukemia; BCR-ABL1; Philadelphia Chromosome; Normal Karyotype; Cytogenetics; ABL1 Mutation; Prognosis