AL-07. Pre-transplant minimal residual disease as an unfavorable prognostic factor in patients with acute myeloid leukemia in the first complete remission

Summary

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially definitive treatment for acute myeloid leukemia (AML). However, more than a third of patients after allo-HSCT relapse, the treatment options for which are limited. Identification of patients at high risk of disease relapse after allo-HSCT and subsequent administration of post-transplant prophylactic therapy (PTT) to them may improve the prognosis. Minimal residual disease (MRD), as determined by multicolor flow cytometry (MCF), is widely used to identify patients with a poor prognosis at all stages of AML treatment. Our aim was to evaluate the results of allo-HSCT in patients with AML depending on the pre-transplant MRD status.

Patients and methods

The study included 182 patients in the first remission of AML who underwent allo-HSCT at the National Medical Research Center for Hematology from September 2015 to July 2023. Characteristics of the patients are shown in Table 1. The analysis of MRD was performed on bone marrow samples using the MPC method, using a combination of approaches: the method of “different from normal” and the search for cells with leukemia-associated phenotype. Overall survival (OS), disease-free survival (DFS) and the probability of relapse (PR) was assessed using the Kaplan-Meier method. Differences were considered statistically significant at p<0.05.

Results

MRD was detected in 37 patients (20%) before allo-HSCT. The results of allo-HSCT in MRD+ patients were significantly worse compared to MRD- (OS: 43% vs. 70%, p<0.0001; DFS: 31% vs. 63%, p<0.0001; PR: 65% vs. 19%, p<0.0001). The intensification of conditioning regimen did not improve the prognosis of MRD+ patients: DFS with MAC – 14%, and with RIC – 36% (p=0.1), PR 82% vs. 60% (p=0.1). When comparing the results of allo-HSCT in MRD+ patients, depending on the type of donor, no significant differences were also obtained (OS: p=0.8; DFS: p=0.5; PR: p=0.4). PTT significantly improved the DFS of MRD+ patients (46% versus 25%, p=0.0470).

Conclusions

MRD+ status is associated with a high risk of relapse, despite the presence of morphological remission before allo-HSCT. The analysis of MRD in patients with AML before allo-HSCT can be used to stratify the risk all-HSCT and identify patients who need post-transplant prophylactic therapy. The development of effective methods for relapse prevention after allo-HSCT is an area of greatest clinical need, which is currently not fully resolved.

Keywords

Minimal residual disease, allogeneic hematopoietic stem cell transplantation, acute myeloid leukemia.