General AML

Prognostic impact of pre- and post-MRD in pediatric AML

The impact of Minimal Residual Disease (MRD) on the outcomes of pediatric Acute Myeloid Leukemia (AML) patients who underwent Allogenic Stem Cell Transplantation (allo-SCT) is not very clear, particularly in the Haploidentical SCT (halpo-SCT) setting.

In a Letter to the Editor of American Journal of Hematology on 20th September 2017, Ying-Jun Chang et al. from the Peking University People’s Hospital & Peking University Institute of Hematology, Beijing, China, discussed results of their study which evaluated the effects of pre- and post- transplantation MRD as determined using Multiparameter Flow Cytometry (MFC) on the outcomes of pediatric AML patients.

Overall, 161 pediatric AML patients who underwent allo-SCT via HLA-matched Sibling Donor (MSDT) or halpo-SCT were analyzed in this study. MRD was evaluated prior to allo-SCT and between 30–180 days after transplantation using MFC.

Patients were classified into four groups depending on their pre-MRD status, MRD negative (MRDneg) or MRD positive (MRDpos), and the source of transplant, MSDT or halpo-SCT. These groups included patients with pre-MRDneg status who received MSDT (group A [n = 6]), pre-MRDpos status who received MSDT (group B [n = 6]), pre-MRDneg status who received Haplo-SCT (group C [n = 115]) and pre-MRDpos status who received haplo-HSCT (group D [n = 34]).

The key results of the study were:
  • Cumulative Incidence of Relapse (CIR) in patients in group A, B, C & D were respectively; 17% vs 100% vs 17% vs 27%, P < 0.01
  • Non Relapse Mortality (NRM) in patients in group A, B, C & D; 0% vs 0% vs 8% vs 3%, P > 0.05
  • Leukemia Free Survival (LFS) in patients in group A, B, C, & D; 83% vs 0% vs 75% vs 70%, P < 0.01
  • Overall Survival (OS) in patients in group A, B, C, & D; 100% vs 25% vs 77% vs 74%, P < 0.01

In summary, positive pre-MRD status with halpo-SCT was associated with a lower CIR and a superior LFS and OS compared to patients who underwent MSDT. Key limitations of the study included its retrospective, single center setting with a small number of patients receiving MSDT, and the non-unform sensitivity of MFC-based MRD detection.

The authors concluded by suggesting that “halpo-SCT may have a strong Graft Versus Leukemia (GVL [reduction of relapse]) effect for pre-MRD positive AML patients in both adult and pediatric” AML patients.

References
  1. Chang Y. J. et al. Effects of Pre- and Post-transplantation Minimal Residual Disease on Outcomes in Pediatric Patients with Acute Myeloid Leukemia Receiving Human Leukocyte Antigen-matched or Mismatched Related Donor Allografts. Am J Hematol. 2017 Sep 20. DOI: 10.1002/ajh.24910. [Epub ahead of print].