The applicability of multiparameter flow cytometry for the detection of minimal residual disease using different‐from‐normal panels to predict relapse in patients with acute myeloid leukemia after allogeneic transplantation

Abstract

Background The MRD status detected using multiparameter flow cytometry (MFC) before allogeneic hematopoietic stem cell transplantation (allo‐HSCT) has crucial prognostic value for patients with acute myeloid leukemia (AML) in morphologic complete remission (CR). We designed a novel panel of antibodies to identify aberrant differentiation/maturation profiles of residual leukemia cells in patients who were not diagnosed at our institution, relapsed with an antigenic shift, or lack leukemia‐associated immunophenotypes. Methods We compared the MRD status detected using MFC and real‐time quantitative polymerase chain reaction (RT‐qPCR) in the same 158 bone marrow samples collected from 44 AML patients carrying leukemia‐specific fusion genes. The clinical performance of the MFC‐based MRD status was analyzed in 168 AML patients who exhibited morphologic CR (135) or active disease (33) before HSCT. Results Strong concordance was found between MFC‐based and RT‐qPCR‐based MRD status (κ = 0.868). Among the patients displaying CR, the positive MRD status detected using MFC was correlated with a worse prognosis [HRs (P values) for relapse, event‐free survival, and overall survival: 4.83 (<0.001), 2.23 (0.003), and 1.79 (0.049), respectively]; the prognosis was similar to patients with an active disease before HSCT. Patients with a positive MRD before HSCT might experience a benefit from developing chronic graft‐vs‐host disease. Conclusions The assessment of MRD using our self‐built different‐from‐normal AML‐MRD detection panel exhibited reliable sensitivity, specificity, and accuracy. In addition, patients with a positive MRD status before transplantation may have higher risk of relapse and worse survival.

Dynamic prediction of relapse in patients with acute leukemias after allogeneic transplantation: Joint model for minimal residual disease

“…All bone marrow samples were evaluated morphologically and with MPFC before alloHSCT (within 7 days before transplantation), and on day 15, 30, 60, 90, 180, 270, and 360 after alloHSCT. MPFC was performed with a panel of antibodies designed for ALL 7,25 or AML 26 . The MRD panel for ALL included CD58‐FITC, KORSA‐PE, CD34‐PerCP, CD20‐PE‐Cy7, CD10‐APC, CD19‐APC‐H7, CD38‐V450, and CD45‐V500 (BD Bioscience and Beckman‐Coulter) 7 .…”

“…Two antibody panels were setup for AML. One panel included CD2/CD7‐FITC (CD2 and CD7 were mixed), CD34‐PE, CD45‐PerCP, CD56‐PE‐Cy7, CD117‐APC, and the other included CD64/CD15‐FITC (CD64 and CD15 were mixed), CD11c‐PE, CD45‐PerCP and CD34‐APC (BD Bioscience and Beckman‐Coulter) 26 . In brief, up to 1.5 million cells in 100‐200 µL of freshly isolated whole bone marrow aspirates was stained with monoclonal antibodies for 15 minutes at room temperature.…”

MRD in Venetoclax-Based Treatment for AML: Does it Really Matter?

“…3). Moreover, many studies highlight the prognostic value of MFC-MRD and MOL-MRD analysis before and after alloSCT (23)(24)(25)(26)(27)(28)(29)(30). Less is known regarding the optimal timing for MRD detection during lower-intensity therapies that usually envisage continuative cycles, until failure, and potentially induce different kinetics of disease response, as compared to conventional chemotherapy.…”

MRD Tailored Therapy in AML: What We Have Learned So Far

“…In the clinical setting, MRD is currently used to refine the complete remission (CR) status that is assessed by morphology ( 74 , 75 ). Most studies show the prognostic value of MFC-MRD and molecular MRD, particularly before transplantation ( 3 , 63 , 76 – 81 ). Measuring MRD at other time points can also have prognostic value and can help to identify a group with poor prognosis, such as MRD measurement after the first chemotherapy ( 3 , 18 , 82 ) and after the consolidation phase ( 3 , 83 , 84 ).…”