scholarly journals Persistence of Minimal Residual Disease Assessed By Multi-Parameter Flow Cytometry (MFC) at 30 and 90 Days after Achieving Complete Remission Predicts Outcome in Patients with Acute Myeloid Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1015-1015
Author(s):  
Pramod Pinnamaneni ◽  
Jeffrey L. Jorgensen ◽  
Hagop M. Kantarjian ◽  
Elias Jabbour ◽  
Sherry R. Pierce ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Minimal Residual Disease ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Response To Therapy ◽  
Minimal Residual ◽  
Acute Myeloid

Abstract Purpose – To determine the value of Minimal Residual Disease (MRD) assessed by Multi-parameter Flow Cytometry (MFC) after achieving initial response to therapy, in predicting outcome in patients with acute myeloid leukemia (AML) Methods – We investigated the predictive value of MRD assessment by MFC in 191 patients with newly diagnosed AML treated between February 2010 and April 2014 at our institution who had available MRD assessment. MRD by MFC was assessed using an 8-color panel containing 19 distinct markers, on bone marrow specimens obtained at the time of achievement of CR and at approximately 30 days and 90 days after achieving CR. Residual leukemic blasts were identified based on phenotypic differences from normal myelomonocytic precursors. Sensitivity was estimated at 0.1% in most cases, with maximum achievable sensitivity of 0.01%, depending on the leukemic phenotype. Results – Of the 191 patients, 167 (87%) achieved complete remission (CR) or CR without platelet recovery (CRp). Their median age was 58 years (Range, 17-85). 84 (44%) were older than 60 years. Median WBC at presentation was 3.2 x 109/L(Range, 0.5-100.2 x 109/L) and median bone marrow blast percentage was 43% (Range, 11-96%). Cytogenetics was favorable risk in 4 (2%), intermediate risk in130 (68%) and adverse risk in 57 (30%). Treatment included cytarabine plus anthracycline in 170 (89%) and hypomethylating agents-based strategies in 21 (11%). 48 patients had available samples at 30 days post CR and 32 (67%) became MRD negative. Achieving MRD negative status was associated with a statistically significant improvement in CR duration (p=0.02) and overall survival (OS) (p=0.0005). 56 patients were evaluated for MRD status at 90 days and 45 (80%) were negative. Again, achieving MRD negative status was associated with a significant improvement in CR duration (p=0.002) and OS (p=0.0009). Conclusion – Achieving MRD negative status by MFC at 30 and 90 days post CR is associated with an improved outcome in patients with AML Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Plasmacytoid Dendritic Cell Burden in the Bone Marrow Predicts End of Induction Minimal Residual Disease Status in Adult Acute Myeloid Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2582-2582
Author(s):  
Papagudi Ganesan Subramanian ◽  
Nikhil Patkar ◽  
Prashant Tembhare ◽  
Yajamanam Badrinath ◽  
Sitaram G Ghogale ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Statistical Analysis ◽  
Minimal Residual Disease ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
High Group ◽  
Viable Cells ◽  
Minimal Residual ◽  
Acute Myeloid

Abstract Introduction: Plasmacytoid dendritic cells (pDCs) are a subset of immune cells that secrete type 1 interferons and serve as antigen presenting cells. In many tumors increased pDC frequencies have been observed and are involved in tumor response initiation. However, there is not much data in acute myeloid leukemia especially in the context of minimal residual disease. Here we evaluated the frequencies of pDCs in the post induction bone marrow and found a significant correlation with MRD levels. Methods: All adult (>18 years ) of patients who were treated for AML [other than AML with t(15;17)] were accrued over a 2 year period. The presence of MRD was assessed using 8 colour flow cytometry on a post induction bone marrows using CD45, CD36, CD38, CD123, CD33, CD117, CD34, HLADR, CD7, CD56, CD13, CD19, CD16, CD11b, CD15 and CD14. Minimum of 500,000 events were acquired/tube on an 8 colour BD FACS Canto II or a 10 colour BC Navios instruments. Kaluza software (v1.3) was used to analyze the .fcs files. MRD was calculated as a percentage of abnormal leukemic cells per total viable cells as gated in forward scatter v side scatter plot. pDCs were calculated as CD123 bright population which expressed HLA-DR (while gating on the progenitors and monocytes based on their expression of CD45 and side scatter). The pDC percentages were counted as a fraction of all viable cells. Based on the results the levels of pDCs were divided into pDC High and pDC Low groups. Statistical analysis was done using Chi squared groups. Results: After exclusion of induction deaths, a total of 94 patients of adult AML was assessed for the presence of MRD at the end of induction. Of these MRD was detected in 48 (51.1%, range 0.01-40%). pDC values ranged from <0.01% to 1.95% (median 0.15%). Median pDC value in the MRD positive group was lower (0.05%) as compared to the MRD negative group (0.23%). Out of 94 patients of 44.7% patients belonged to the pDC Low group of which majority patients were MRD positive (66.7% of the pDC Low group). Similarly majority of patients in the pDC High group were MRD negative (61.5% of the pDC High group). A statistical analysis of these categories was also found to be significant (p=0.008) Conclusion: These pilot data seem to indicate that the pDC burden in the bone marrow may have a role in influencing MRD clearance in the bone marrow. A detailed investigation of the pDC function in the bone marrow microenvironment is warranted. Disclosures No relevant conflicts of interest to declare.

Prognostic Impact of Pretransplantation Minimal Residual Disease Detection for Flow Cytometric, on Outcome of Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia. a Single Center Experience in Colombia over 14 Years

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5411-5411
Author(s):  
Andres Armando Borda Molina ◽  
Iris Cordoba ◽  
Virginia Abello ◽  
Carmen Rosales ◽  
Rosales Manuel ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Minimal Residual Disease ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Prognostic Impact ◽  
Allogeneic Bone ◽  
Flow Cytometric ◽  
Minimal Residual ◽  
Acute Myeloid

Abstract Background: The accumulated evidence from studies of multiparameter flow cytometric MRD (MFC-MRD) assessment in AML leaves little doubt that this method of MRD detection can be used to risk stratify both younger and older patients at treatment time points. Persistence of disease or high levels of pretransplantation minimal residual disease (MRD) have been reported to predict disease relapse after Allogeneic bone marrow transplantation (BMT). The prognostic impact of MFC-MRD is strong enough to have emerged despite study differences in the MFC assays and the limitations of now outdated restricted antibody panels. Aims: To determine the value of Minimal Residual Disease (MRD) assessed by Multi-parameter Flow Cytometry (MFC) pretransplantation Allogeneic BMT, in predicting outcome in patients with acute myeloid leukemia (AML). Methods: We performed a retrospective analysis the predictive value of MRD assessment by MFC pre trasnplantation alogeneic in 119 patients (diagnosed AML treated between january 2010 and october 2014 submitted at our institution who had available MRD assessment). MRD by MFC on bone marrow specimens obtained approximately 30 days before transplantation. MRD was identified as a cell population showing deviation from normal antigen expression patters compared with normal or regenerating marrow. The detection threshold for defining pre transplantation positive MRD was >0.3%. Results - Of the 119 patients, 80 (67%) were in complete remission (CR1) , 31 (26%) CR2 and > CR2 8 (6%). Their median age was 38 years (Range, 10-64). Hyperleucocytosis in 39 (32%) and Cytogenetics was favorable risk in 32 (26%), intermediate risk in 39 (32.%), adverse risk in 35 (29%) and unknown in 13 (14%). There were a total of 44 deaths and 17 relapses; these contributed to the probability estimates for overall survival (OS) and disease free survival (DFS), stratified by MRD status and shown in figure 1. The median follow-up after BMT among survivors was 8.3 years (range, 6.9 to 9,6 years). The 7.5-years estimates of OS for MRD-positive and MRD-negative patients were 43.1% (range, 23,2% to 58,6%) and 68% (range 56% to 78.3%), respectively, and the 7,5 year estimates for DFS for MRD-positive and MRD-negative patients were 40.5% (range 21.4% to 52.6%) and 56% (range 42.5% to 65.8%). After adjustment for various covariates, age, cytogenetics risk, hyperleucocytosis, secundary AML, the hazard ratios of MRD positive versus MRD negative were 2.06 (range 1.52 to 6.24; P=0,003) for overall mortality, 3.45 ( range 2.14 to 7.32; p=0.014) for DFS. Conclusion: That detection of MRD pre transplantation define a population of patients with AML who are at higher risk for adverse outcome, even after adjusting for other factors that influence post-BMT outcome. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Impact of Minimal Residual Disease and Chimerism Monitoring at Different Timepoints after Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-7
Author(s):  
Reyes María Martín-Rojas ◽  
Gillen Oarbeascoa ◽  
Rebeca Bailén ◽  
Ignacio Gómez-Centurión ◽  
Luis Miguel Juarez ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Cumulative Incidence ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Minimal Residual ◽  
Risk Of Relapse ◽  
Acute Myeloid

¶ Martin-Rojas RM and Oarbeascoa G contributed equally to this work. INTRODUCTION Relapse is the main cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia (AML). The evaluation of minimal residual disease (MRD) could provide a more accurate assessment of the depth of response, and therefore identify patients with higher risk of relapse. AIMS The aim of our study was to analyze the impact of pre-HSCT flow cytometry (FCM) and molecular MRD together with chimerism and MRD in the early post-HSCT period in patients with AML. METHODS We conducted a retrospective study in patients with complete remission AML who underwent a HSCT between 2008 and 2019 in our center. MRD was analyzed by flow cytometry in bone marrow aspirates and by quantitative RT-PCR (NMP1, RUNX1-RUNX1T1, CBFB-MYH11, KMT2A-MLLT3, WT1) in bone marrow aspirates and/or peripheral blood. MRD was determined within the 30 days preceding the HSCT and at day +30 and +90 post-HSCT. Bone marrow and selected CD34+ lineage chimerism was analyzed by STR (AmpFISTR SGM Plus, Thermo Fisher) at days +30 and +90 post-HSCT. This study was approved by our Institutional Ethics Committee. Data were analyzed using IBM SPSS Statistics version 24 and R version 3.5.1. RESULTS A total of 115 patients were analyzed. Pre-HSCT MRD was negative in 58 patients (50.4%) and positive in 57 patients (49.6%). We found no statistically significant differences in the characteristics between the two groups (Table 1). Median follow up was 39 months (IQR 10.4-55.8). 3-year overall survival (OS) for patients with pre-HSCT negative MRD was 72.5% versus 70.3% in patients with positive MRD (p=0.41), with an event free survival (EFS) of 66.9% versus 66.1 (p=0.48) respectively (Figure 1). Median time to the beginning of immunosuppression withdrawal was 82.5 days (IQR 59-93) for patients with negative MRD and 68 days (IQR 55.3-85.3) for patients with positive MRD (p&lt;0.001). The cumulative incidence of grade II-IV acute graft versus host disease (aGVHD) and moderate-severe chronic GVHD did not show statistically significant differences based on the MRD status. Similarly, the cumulative incidence of relapse and the 2-year mortality was not significantly different between the two groups. Patients with negative MRD at day +30 showed a 2-year OS of 83.5% versus 58.1% in patients with positive MRD (p=0.03) and a EFS of 79.9% versus 48.6% (Figure 2). The cumulative incidence of relapse was more elevated in patients with positive MRD (29.8% versus 13.6%) at day +30. Patients with mixed chimerism (MC) at day +30 showed a significantly lower 3-year OS and EFS than patients with complete chimerism (CC). Likewise, the cumulative incidence of relapse was significantly higher in patients with MC, both if detected in bone marrow aspirate and in CD34+ cells. The multivariate analysis revealed that MRD status at day +30 post-HSCT was an independent prognostic factor for EFS (HR 3.74; 95% CI 1.38-10.1; p=0.009). CONCLUSIONS Patients with AML presenting a positive MRD in the early post-HSCT period and those who show a MC at day +30 post-HSCT have lower EFS, with positive MRD at day +30 being an independent prognostic factor for EFS. The evaluation of MRD and chimerism in the early post-HSCT period is useful to identify patients with higher risk of relapse, who may take advantage of preemptive measures. Disclosures Kwon: Gilead, Novartis, Pfizer, Jazz: Consultancy, Honoraria.

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