The prognostic effect of minimal residual disease detected by multiparameter flow cytometry before allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia patients in first complete remission
Zoya V. Konova, Elena N. Parovichnikova, Irina V. Galtseva, Yulia O. Davydova, Nikolay M. Kapranov, Vera A. Vasilyeva, Maria V. Dovydenko, Olga M. Koroleva, Uliyana V. Maslikova, Natalia N. Popova, Mikhail Yu. Drokov, Ekaterina D. Mikhaltsova, Anna A. Dmitrova, Olga S. Starikova, Darya S. Dubnyak, Larisa A. Kuzmina, Valery G. Savchenko
National Research Center for Hematology, Moscow, Russia
Contact: Dr. Zoya V. Konova
One of the main causes of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia (AML) is the disease relapse. Identification of the patients with high relapse risk after allo-HSCT is an important approach to improve the clinical outcome by administration of preemptive posttransplantation treatment. Over recent years, minimal residual disease (MRD) detected by multiparameter flow cytometry (MFC) has been widely used to identify patients with poor prognosis due to its simplicity and wide availability. Aim of this work was to evaluate the prognostic effect of MRD status before allo-HSCT on clinical outcomes for AML patients.
Patients and methods
In our statistical analysis we included 60 AML patients who underwent allo-HSCT in National Research Center for Hematology between July 2016 and July 2019. Patient’s characteristics are summarized in Table 1. All these patients were in first complete morphologic remission at the time of allo-HSCT. Bone marrow samples were obtained before allo-HSCT and were analyzed by the 6-color MFC (BD FACS Canto II, USA). Positive MRD was identified as a cell population deviating from the normal patterns of antigen expression in distinct cell lineages at specific stages of maturation for all patients. For patients with LAIP at diagnosis, positive MRD was also defined as a cell population carrying LAIP markers at diagnosis. The probabilities of overall survival (OS) and relapse free survival (RFS) were estimated using the Kaplan-Meier method.
Table 1. Patient’s characteristics
13 patients (21.7%) before allo-HSCT were identified as MRD positive (MRD+). Subsequently 6 of them (46.2%) relapsed. The relapse was also registered in 2 out of 47 MRD negative (MRD-) patients (4.3%). Statistical analysis revealed significant differences between MRD- and MRD+ patients: MRD+ had much worse OS (42% vs 89%, p=0.0120, Fig. 1A) and RFS (32% vs 94%, p<0.0001, Fig. 1B). The relapse probability was extremely high among MRD+ patients (68% vs 6%, p<0.0001, Fig. 1C).
MRD detected by MFC is a strong prognostic factor of increased risk of relapse and may reflect OS and RFS in patients with AML after allo-HSCT. Despite the presence of morphological CR before allo-HSCT, MRD persistence before allo-HSCT was associated with high relapse risk. Accordingly, testing for MRD before allo-HSCT may help to identify a subgroup of patients who need preemptive treatment after allo-HSCT.
No relevant conflicts of interest to declare.
Minimal residual disease, allogeneic hematopoietic stem cell transplantation, acute myeloid leukemia.