Impact of pre-transplantation minimal residual disease (MRD) on the outcome of Allogeneic hematopoietic stem cell transplantation for acute leukemia

Hematology. 2021 Dec;26(1):295-300. doi: 10.1080/16078454.2021.1889162.

Abstract

Objective: To investigate the impact of minimal residual disease (MRD) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the outcome of acute leukemia.

Methods: Data from 114 patients who were diagnosed with acute leukemia (AL) and underwent allo-HSCT between Jan 2013 and Dec 2019 were collected and analyzed. The patients were attributed into MRD positive (MRD+) group and MRD negative (MRD-) group.

Results: Among the 114 acute leukemia patients, there were 32 MRD+ patients before transplantation, and 82 MRD- patients. No significant difference was found between the MRD+ group and the MRD- group in the incidence of acute graft-versus-host disease (aGvHD) (p = 0.09). Compared with the MRD+ group, the MRD- group had a higher incidence of chronic graft-versus-host disease (cGvHD) (p = 0.008). There is no significance in relapse between the two groups (p = 0.084), while the incidence of relapse was seemingly higher in the MRD+ group: 36.9% Vs 19.7% . We attributed to the lack of sample size and NRM in MRD+ group was remarkably higher. The MRD+ group had significantly worse one-year overall survival (OS) ( , p = 0.003) and one-year progression-free survival (PFS) (, p = 0.009). In the multivariate analysis, MRD+ was an independent prognostic factor for OS (HR = 1.898; 95%CI 1.042-3.457; p = 0.036).

Conclusion: Pre-transplantation MRD positive status is a risk factor for survival and prognosis after HSCT. Upon this, emphasis should be put on (1) screening more efficient chemo regimen with targeted agents, to help patients reach and keep MRD- status before transplantation; (2) designing better management with different GvHD prophylaxis treatment, timely disease monitoring and preemptive intervention on relapse.

Keywords: Minimal residue disease (MRD); acute leukemia; flow cytometry; graft-versus-host disease; hematopoietic stem cell transplantation (HSCT); overall survival; prognosis; relapse.

MeSH terms

  • Adolescent
  • Adult
  • Female
  • Graft vs Host Disease / etiology
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Middle Aged
  • Neoplasm, Residual / diagnosis
  • Neoplasm, Residual / therapy*
  • Prognosis
  • Transplantation, Homologous / adverse effects
  • Treatment Outcome
  • Young Adult