The Quantification of Minimal Residual Disease Pre- and Post-Unmanipulated Haploidentical Allograft by Multiparameter Flow Cytometry in Pediatric Acute Lymphoblastic Leukemia

Cytometry B Clin Cytom. 2020 Jan;98(1):75-87. doi: 10.1002/cyto.b.21840. Epub 2019 Aug 19.

Abstract

Background: This study aimed to determine the impact of the pre- and post-minimal residual disease (MRD) status as well as the peri-transplant MRD kinetics on clinical outcomes in pediatric ALL patients who received haploidentical allografts.

Methods: A retrospective study (n = 166) was performed. MRD was determined using multiparameter flow cytometry.

Results: Pediatric ALL patients with pre-MRDneg had a lower cumulative incidences of relapse (CIR) compared to those with pre-MRDpos (19.7% vs. 41.2%, P = 0.009). Compared to post-MRDneg group, patients with post-MRDpos experienced higher CIR (81.0% vs. 15.9%, P < 0.001), inferior LFS (14.3% vs. 66.9%, P < 0.001) and OS (19.1% vs. 66.9%, P < 0.001). In regard to peri-MRD kinetics, compared with the MRD-decreasing group and MRDneg/MRDneg group, MRD-increasing group had higher CIR, lower probabilities of LFS and OS (P < 0.001). Compared to pre-MRDneg/post-MRDneg group, a higher CIR was found in the pre-MRDpos/post-MRDpos group (66.7% vs. 12.5%, P < 0.001), pre-MRDpos/post-MRDneg group (32.0% vs. 12.5%, P = 0.016), and pre-MRDneg/post-MRDpos group (91.7% vs. 12.5%, P < 0.001). A lower incidence of LFS and OS were found in pre-MRDpos/post-MRDpos group and pre-MRDneg/post-MRDpos group than in pre-MRDneg/post-MRDneg group (P < 0.05). Multivariate analyses confirmed the association of pre-MRD status, post-MRD status, and peri-MRD kinetics with outcomes (P < 0.05).

Conclusions: The results indicate that, in the pediatric ALL subgroup, not only pre-MRD status or post-MRD status but also peri-SCT MRD dynamics, were associated with an increased CIR after haploidentical allografts. Patients are put into different risk group based on MRD kinetics versus single time MRD status. © 2019 International Clinical Cytometry Society.

Keywords: allogeneic stem cell transplantation; minimal residual disease; multiparameter flow cytometry; pediatric acute lymphoblastic leukemia; unmanipulated haploidentical allografts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Allografts / pathology*
  • Allografts / transplantation*
  • Child
  • Child, Preschool
  • Female
  • Flow Cytometry / methods
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Male
  • Neoplasm, Residual / pathology*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology*
  • Recurrence
  • Retrospective Studies
  • Transplantation, Homologous / methods