Work

Prognostic Value of Multicolor-Flow Cytometric Measurable Residual Disease Detection in Acute Myeloid Leukemia Prior to Allogeneic Hematopoietic Cell Transplantation: Potential Role of HLA-DR

Year: 2025

Type: article

Abstract: Long abstract Introduction The prognosis of patients with acute myeloid leukemia (AML) undergoing alogeneic hematopoietic cell transplantation (alloHCT) is multifaceted, determined by patient-related factors, disease characteristics, and treatment response. Measurable residual disease (MRD) assessment, particularly before alloHCT, is crucial for outcome prediction and treatment optimization. Aims The aim of the presented study was to assess the prognostic value of MRD detection by multicolor flow cytometry (MFC) before alloHCT in AML patients, and to irvestigate the influence of reduced HLA-DR expression on leukernic cells, as a possible immune escape mecharism, on post-transplant outcome. Methods We implemented a standardized, reproducible, and rapid MFC approach to monitor MRD before alloHCT. Patient and AML characteristics, as well as outcome parameters were extracted from electronic health records and an AML registry. Sample preparation and acquisition followed established protocols. Results A total of 185 patients were included in this analysis, including 69 patients with an increased blast percentage, as the prognostic significance of cytomorphological remission for alloHCT outcomes has recently been questioned. MRD positivity before alloHCT (MRD pos ) significantlycorrelated with inferior overall survival (OS) and relapse-free survival (RFS). Specifically, the 2-year OS rate of the MRD pos cohort was significantly lower compared to MRD neg patients (65% vs. 89%, HR4.3, Cl 1.7=10.6, p<0.01). In the cohort of patients in hematologic remission before alloHCT (n=116), MRD pos patients had a higher relapse rate compared to MRD neg patients (33% vs. 14%, p=0.03), also leading to a significantly shorter 2-year OS (56% vs. 88%, HR2.8, Cl 1.1-7.4, p=0.04) and 2-year RFS (59% vs. 81%, HR 2.1, Cl 1.0-4.2, p=0.05). The prognostic significance of MRD status was preserved in multivariable Cox regression models. Of note, MRD pos patients with preserved HLA-DR expression on residual leukemic cells before alloHCT (n=14) had a favorable 2-year OS compared to those MRD pos patients with HLA-DR loss (93% vs. 62%, HR 0.3, Cl 0.1-1.2, p=0.08). Molecular MRD assessment complemented MFC-based methods, with concordant results in 75\% of patients. Conclusions Our rapid semi-automated method of MRD evaluation by MFC allows a personalized risk prediction in AML patients undergoing alloHCT as a potential base for individual treatment strategies. The association between pre-transplant HLA-DR expression on residual leukemic cells and post-transplant outcome indicates a possible interaction between phenotype and Graft-versus-Leukemia effect. Further research is warranted to elucidate the mechanistic basis of immune escape and its implications for post-transplant relapse, guiding the development of novel therapeutic strategies. Short abstract The prognosis of AML patients undergoing alloHCT is determined by patient-related factors, disease characteristics and treatment response. MRD assessment is crucial for outcome prediction and treatment optimization. We implemented a standardized, reproducible, and rapid multicolor-flow cytometric (MFC) approach to monitor MRD during and after treatment. MRD positivity before alloHCT significantly correlated with inferior OS and RFS and exceeded the predictive power of cytomorphology. Furthermore, the detection of HLA-DR on residual leukemic cells before alloHCT was associated with superior outcome, comparable to MRD negative patients. HLA-DR is known to be involved in crucial immune mediated processes following alloHCT, e.g. the Graft-versus-Leukemia effect (GvL). In addition, it shows that pre-existing factors related to immunogenicity and antigen presentation might impact post-transplant outcome. Our study highlights that the mere knowledge on MRD quantity is not sufficient for exact risk stratification in the context of alloHCT, but that the qualitative properties of remaining leukemic cells like the immunogenic potential further shape the transplant-associated prognosis. In conclusion, comprehensive MRD evaluation by MFC might facilitate personalized treatment strategies in AML patients undergoing alloHCT. Further research is warranted to elucidate the mechanistic basis of immune escape and its implications for post-transplant relapse, guiding the development of novel therapeutic strategies.

Source: Clinical Lymphoma Myeloma & Leukemia

DOI: 10.1016/j.clml.2025.08.013