Dynamics of minimal residual disease defines a novel risk-classification and the role of allo-HSCT in adult Ph-negative B-cell acute lymphoblastic leukemia

Abstract

The prognosis of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) patients is well established. However, the implementation of dynamic MRD for risk classification and decision-making for allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains vague. In this study, we collected multiparameter flow cytometry (MFC)-MRD data of Ph-negative B-ALL patients (n = 134) from the Precision-Classification-Directed-Target-Total-Therapy-ALL-2016 (PDT-ALL-2016) cohort and stratified it into high-(HR), medium-(MR), and standard-risk (SR) groups. With a median of 3.65 years follow-up (95% CI: 3.037–4.263), 3-year OS rate was 51.8 ± 8.3% in HR, compared with MR 61.5 ± 10.8% (p = 0.472), and SR 73.3 ± 5.9% (p = 0.006). Multivariate analysis shows that integrated dynamic MRD is an independent factor for overall survival. Compared to pediatric-inspired chemotherapy, allo-HSCT significantly improves the survival of the HR cohort (p < 0.001), but not in MR and SR. Finally, our study suggests that integrated dynamic MRD defines a novel risk-classification criteria and highlights the benefits of allo-HSCT in adult patients with Ph-negative ALL.

Keywords:

• Minimal residual disease
• Philadelphia chromosome-negative
• adult B-cell acute lymphoblastic leukemia
• allogeneic hematopoietic stem cell transplantation

Acknowledgements

We express our sincere gratitude to all members of our study team for their whole-hearted cooperation. We acknowledge the contribution of the medical and nursing staff of Nanfang Hospital for their support and follow up on patients.

Disclosure statement

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

Additional information

Funding

This work was supported by National Natural Science Foundation of China [81770170,81970147,82170163], Science and Technology Planning Project of Guangdong [2017A030313601], Clinical Trial Funding of SMU [2016A020215112], Clinical Trial Funding of Nanfang Hospital [LC2016ZD009/2019CR012].