AW-02. Impact of minimal residual disease on outcomes of allogeneic hematopoietic stem cell transplantation

Summary

Introduction

In recent years, minimal residual disease (MRD) detected by multiparameter flow cytometry (MFC) has been widely used to identify acute leukemia (AL) patients with poor prognosis and to correct therapeutic tactics. This is due to its availability and the possibility of performing the study in a short time. However, there is evidence of an independent effect of pre-transplant MRD-status on the results of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The aim of present work was to assess the impact of pre-transplant MRD status on the long-term results of allo-HSCT.

Patients and methods

The study included 170 patients: 107 patients with acute myeloid leukemia (AML) and 63 patients with acute lymphoblastic leukemia (ALL), who underwent allo-HSCT National Research Center for Hematology between September 2015 and June 2020. Patient characteristics are shown in Table 1.

Table 1. Patient’s characteristics

All the patients were in complete morphological remission (CR) at the time of allo-HSCT. 91 patients with AML and 37 patients with ALL were in the first CR at the time of transplantation, in the second, and more CR were in 16 and 26 cases, respectively. The median follow-up was 16 (1-47) months for AML and 11.7 (1-52) months for ALL. Immunophenotypic study was performed using 6-color multicolour flow cytometry (MFC) assessed with BD FACS Canto II system (USA) in bone marrow samples obtained before allo-HSCT. MRD was detected using a combination of the “different-from-normal” and LAIP methods. Statistical analysis was performed using SPSS ver. 23 (IBM, Chicago, Ill., USA). Cox proportional hazards model was used to assess the influence of various independent factors on the probability of relapse/death from any cause. The factors included into the model: disease status, donor type, conditioning regimen, source of graft, pre-transplant MRD status, age, acute or chronic graft-versus-host disease (GvHD). The value of p<0.05 was considered significant.

Results

In our study, the presence of MRD before allo-HSCT (HR=4.043 [2.142-7.631], p <0.0001) and disease status (HR=1.967 [1.010-3.830], p=0.047) proved to be independent factors of poor prognosis. On the contrary, it was noted that the development of chronic GvHD, reduces the probability of relapse/death, especially if it does not require systemic therapy with glucocorticosteroides (HR=0.182 [0.052-0.639], p=0.008). The results are shown in Table 2.

Table 2. Impact of various independent factors on the probability of relapse/death from any cause (Cox proportional hazards model)

Conclusions

MRD detected by MFC seems to be a strong prognostic factor of increased relapse risk. Testing for MRD before allo-HSCT is necessary to stratify the risk of allo-HSCT and identify patients with AML and ALL who should require a preemptive post-transplant therapy in order to prevent the disease relapse.

Keywords

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