KINETICS OF MINIMAL RESIDUAL DISEASE BEFORE AND AFTER HEMATOPOIETIC CELL TRANSPLANTATION

Abstract

Introduction: Minimal residual disease (MRD) detected before and after hematopoietic stem cell transplantation (HSCT) is associated with poor outcomes in high-risk acute leukemia. This study prospectively evaluates the impact of MRD accessed by multiparameter flow cytometry (MFC) in a reference hospital in southern Brazil. Methods: Prospective analysis of 67 consecutive patients transplanted between 2019/Jun and 2022/Jun, with high-sensitive MFC analysis in the month before HSCT. Pre-transplant MRD was negative (MRD-) in 34 (50.7%) and positive (MRD+) in 33 (49.3%) patients (14 ALL and 18 AML). Posttransplant MRD evaluation showed MRD+ in five patients at d30 (5/26, 19.2%), two (2/23, 8.7%) at d60 and 5 (5/57, 8.8%) at d100. Results: There were no differences concerning pretransplant variables between positive and negative MRD pre-HSCT groups. Considering alive patients at d100: Pre-HSCT MRD negative versus posttransplant kinetic: Considering patients available at d100 (n = 57) in relation to pre-transplant MRD status, almost half (n = 30/57, 52.6%) had negative MRD both before and after transplantation. Two AML patients MRD negative became positive and subsequently relapsed, at d488 and d426. Both patients had AML with negative CD34, but this LAIP was not known prior to relapse. Pre-HSCT MRD positive versus posttransplant kinetic: In relation to the 27 patients with positive disease before transplantation who were alive at d100 (n = 27/35, 77.1%), the majority (n = 22/27, 81.5%) became MRD negative, suggesting minimal residual disease clearance in response to treatment. Four patients MRD+ relapsed within the first year after transplantation (d117, d136, d168 and d347) and two other two patients relapsed on d405 and d744. Cumulative incidence of relapse in total cohort was 11.4%, NRM was 22.4% and probabilities of EFS and OS were 64.2% and 70.4%, respectively. MRD positivity before transplantation was associated with decreased OS (88.2% versus 51.5%, p = 0.001) and EFS (82.4% versus 45.5%, p = 0.001), but relapse was not different (5.9% vs 18.2%, p = 0.036); non-relapse mortality was 8.8% vs 36.4% (p = 0.003). Extended follow-up showed a high risk of disease relapse in AML MRD+ subgroup (EFS 78.6% vs 36.8%, p < 0.001, and OS 92.9% vs 47.4%, p = 0.001), and this was associated to MRD positivity at d100. MRD analysis before transplantation had a high sensitivity (75%) in predicting survival, while MRD positivity at d100 was more specific in predicting subsequent relapse (90.5%) in this cohort. Conclusion: A highly sensitive assessment of MRD before HSCT in a real-life setting allowed the correct identification of patients with poor prognosis. Moreover, the persistence of MRD after transplantation identified patients at risk of relapse.