MRD Monitoring for Potential for Relapse Following Allogeneic Hematopoietic Cell Transplantation Among Patients With AML

According to a study published in Blood, a detection benefit was shown in next-generation sequencing (NGS) monitoring of (MRD) as related to potential for relapse for patients with acute myeloid leukemia (AML) after allogeneic hematopoietic cell transplantation (alloHCT), which supports monthly monitoring utilizing all variants known from diagnosis. Study authors found that mutations in epigenetic modifier genes in AML exhibited a higher incidence of MRD positivity and greater stability before relapse, where mutations in signaling genes demonstrated a shorter lead time to relapse.

“Patients with [AML] who experience relapse following allogeneic hematopoietic cell transplantation face unfavorable outcomes regardless of the chosen relapse treatment. Early detection of relapse at the molecular level by [MRD] assessment enables timely intervention, which may prevent hematological recurrence of the disease,” stated lead study author Clara Philine Wienecke, Hannover Medical School, Hannover, Germany, and colleagues.

This analysis was undertaken in order for authors to assess the question of whether molecular MRD assessment can detect MRD before an impending relapse—and if it can, how long before. This study examines and categorizes the molecular architecture and kinetics prior to AML relapse by using error-corrected NGS in 74 patients with AML relapsing after alloHCT. Investigators evaluated 140 samples from peripheral blood collected 0.6 to 14 months before relapse.

Study results demonstrated at least 1 MRD marker became detectable in 10%, 38%, and 64% of patients at 6, 3, and 1 month(s) before relapse, respectively. Additionally, by translating these proportions into monitoring intervals, 38% of relapses would have been detected through MRD monitoring every 3 months, whereas 64% of relapses would have been detected with monthly intervals. Researchers noted the relapse kinetics following alloHCT were influenced by the functional class of mutations and their stability during molecular progression.

“Notably, mutations in epigenetic modifier genes exhibited a higher prevalence of MRD positivity and greater stability before relapse, whereas mutations in signaling genes demonstrated a shorter lead time to relapse. Both DTA (DNMT3A, TET2, and ASXL1) and non-DTA mutations displayed similar relapse kinetics during the follow-up period after alloHCT,” concluded Dr Wienecke and colleagues.

“Our study sets a framework for MRD monitoring after alloHCT by NGS, supporting monthly monitoring from peripheral blood using all variants that are known from diagnosis,” they added.

Source:

Wienecke C, Heida B, Venturini L, et al. Clonal relapse dynamics in acute myeloid leukemia following allogeneic hematopoietic cell transplantation. Published online July 18, 2024. doi: 10.1182/blood.2023022697