Prognostic value of MRD monitoring based on BCR-ABL1 copy numbers in Philadelphia chromosome positive acute lymphoblastic leukemia

Abstract

Assessment of measurable residual disease (MRD) has emerged as a powerful prognostic tool in pediatric and adult acute lymphoblastic leukemia (ALL). In this single-centre retrospective study, we evaluated the prognostic relevance of MRD based on BCR-ABL1 copy numbers in Ph + ALL patients between 2006 and 2018. Molecular responses were evaluated at 3, 6, 9 and 12 months after the initiation of treatment. Patients who had their MRD assessed at three or more time points were categorized into MRD good risk or poor risk based on BCR-ABL1/ABL1 copy number ratio. MRD positive patients consistently showed a trend toward poor survival and on multivariate analysis, MRD poor risk patients had adverse outcomes when compared to MRD good risk patients in terms of overall (OS; p = .031) and event-free (EFS; p < .001) survival. In conclusion, molecular MRD based on BCR-ABL1 copy number ratio is an ideal prognostic indicator in Ph + ALL patients undergoing treatment.

Keywords:

• Ph + ALL
• BCR-ABL1
• minimal residual disease
• RQ-PCR

Acknowledgements

The authors would like to thank Ms Senthamizhselvi Anandan and other staffs of leukemia, flow cytometry and cytogenetics labs. The study was presented as an abstract in the 59th Annual Conference of Indian Society of Hematology & Blood Transfusion.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

AKA: Conceptual development of the study, performed research, collected and analyzed the data, wrote the paper. NBJ: performed research, provided cytogenetic inputs. KML: performed research, biostatistics for the study. AK: performed research, clinical data analysis. FNA: performed research, clinical data accrual and analysis. UPK: performed research, clinical data accrual and analysis. AA: performed research, clinical data accrual and analysis. BG: performed research, clinical data accrual and analysis. PB: Conceptual development of the study, performed research, analyzed the data, reviewed the paper. VM: Conceptual development of the study, provided the clinical inputs, analyzed the data, wrote and reviewed the paper.

Additional information

Funding

This study is supported in part by a DBT-COE grant (BT/COE/34/SP13432/2015), New Delhi, India and Indian Council of Medical Research Centre for Advanced Research grant 70/14/14-CAR to PB. VM is supported by senior fellowship program of Wellcome DBT India Alliance (IA/CPHS/18/1/503930), New Delhi, India. PB is supported by a senior fellowship program of Wellcome DBT India Alliance (IA/S/15/1/501842) New Delhi, India. UPK is supported by an early career fellowship program of Wellcome DBT India Alliance (IA/CPHE/17/1/503351), New Delhi, India.