Early immunophenotypical evaluation of minimal residual disease in acute myeloid leukemia identifies different patient risk groups and may contribute to postinduction treatment stratification

Blood ◽  
2001 ◽  
Vol 98 (6) ◽  
pp. 1746-1751 ◽  
Author(s):  
Jesús F. San Miguel ◽  
Marı́a B. Vidriales ◽  
Consuelo López-Berges ◽  
Joaquı́n Dı́az-Mediavilla ◽  
Norma Gutiérrez ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Minimal Residual Disease ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Response To Therapy ◽  
Low Risk ◽  
Prognostic Impact ◽  
Minimal Residual ◽  
Acute Myeloid

Abstract Early response to therapy is one of the most important prognostic factors in acute leukemia. It is hypothesized that early immunophenotypical evaluation may help identify patients at high risk for relapse from those who may remain in complete remission (CR). Using multiparametric flow cytometry, the level of minimal residual disease (MRD) was evaluated in the first bone marrow (BM) in morphologic CR obtained after induction treatment from 126 patients with acute myeloid leukemia (AML) who displayed aberrant phenotypes at diagnosis. Based on MRD level, 4 different risk categories were identified: 8 patients were at very low risk (fewer than 10−4 cells), and none have relapsed thus far; 37 were at low risk (10−4 to 10−3 cells); and 64 were at intermediate risk (fewer than 10−3 to 10−2 cells), with 3-year cumulative relapse rates of 14% and 50%, respectively. The remaining 17 patients were in the high-risk group (more than 10−2 residual aberrant cells) and had a 3-year relapse rate of 84% (P = .0001). MRD level not only influences relapse-free survival but also overall survival (P = .003). The adverse prognostic impact was also observed when M3 and non-M3 patients with AML were separately analyzed, and was associated with adverse cytogenetic subtypes, 2 or more cycles to achieve CR, and high white blood cell counts. Multivariate analysis showed that MRD level was the most powerful independent prognostic factor, followed by cytogenetics and number of cycles to achieve CR. In conclusion, immunophenotypical investigation of MRD in the first BM in mCR obtained after AML induction therapy provides important information for risk assessment in patients with AML.

scholarly journals MINIMAL RESIDUAL DISEASE IN ACUTE MYELOID LEUKEMIA OF ADULTS: DETERMINATION, PROGNOSTIC IMPACT AND CLINICAL APPLICATIONS.

2016 ◽  
Vol 8 ◽  
pp. 2016052 ◽  
Author(s):  
Maria Ilaria Del Principe
Keyword(s):  
Acute Myeloid Leukemia ◽  
Minimal Residual Disease ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Clinical Applications ◽  
Response To Therapy ◽  
Prognostic Impact ◽  
Allocation Process ◽  
Minimal Residual ◽  
Acute Myeloid

Pretreatment assessment of cytogenetic/genetic signature of acute myeloid leukemia (AML) has been consistently shown to play a major prognostic role but also to fail at predicting outcome on individual basis, even in low-risk AML. Therefore, we are in need of further accurate methods to refine the patients’ risk allocation process, distinguishing more adequately those who are likely to recur from those who are not. In this view, there is now evidence that the submicroscopic amounts of leukemic cells (called minimal residual disease, MRD), measured during the course of treatment, indicate the quality of response to therapy. Therefore, MRD might serve as an independent, additional biomarker to help identifying patients at higher risk of relapse. Detection of MRD requires the use of highly sensitive ancillary techniques, such as polymerase chain reaction (PCR) and multiparametric flow cytometry (MPFC). In the present manuscript, we will review the current approaches to investigate MRD and its clinical applications in AML management.

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.

Prognostic Impact of Minimal Residual Disease inCBFB-MYH11–Positive Acute Myeloid Leukemia

2010 ◽  
Vol 28 (23) ◽  
pp. 3724-3729 ◽  
Author(s):  
Andrea Corbacioglu ◽  
Claudia Scholl ◽  
Richard F. Schlenk ◽  
Karina Eiwen ◽  
Juan Du ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Minimal Residual Disease ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Prognostic Impact ◽  
Consolidation Therapy ◽  
Old Patients ◽  
Minimal Residual ◽  
Acute Myeloid

PurposeTo evaluate the prognostic impact of minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) expressing the CBFB-MYH11 fusion transcript.Patients and MethodsQuantitative reverse transcriptase polymerase chain reaction (PCR) was performed on 684 bone marrow (BM; n = 331) and/or peripheral blood (PB; n = 353) samples (median, 13 samples per patient) from 53 younger adult (16 to 60 years old) patients with AML treated in prospective German-Austrian AML Study Group treatment trials. Samples were obtained at diagnosis (BM, n = 45; PB, n = 48), during treatment course (BM, n = 153; PB, n = 122), and at follow-up (BM, n = 133; PB, n = 183). To evaluate the applicability of PB for MRD detection, 198 paired BM and PB samples obtained at identical time points were analyzed.ResultsThe following three clinically relevant checkpoints were identified during consolidation and early follow-up that predicted relapse: achievement of PCR negativity in at least one BM sample during consolidation therapy (2-year relapse-free survival [RFS], 79% v 54% for PCR positivity; P = .035); achievement of PCR negativity in at least two BM or PB samples during consolidation therapy and early follow-up (≤ 3 months; 2-year RFS, P = .001; overall survival, P = .01); and conversion from PCR negativity to PCR positivity with copy ratios of more than 10 after consolidation therapy. Analysis of paired BM and PB samples revealed BM samples to be more sensitive during the course of therapy, whereas for follow-up, PB samples were equally informative.ConclusionWe defined clinically relevant MRD checkpoints that allow for the identification of patients with CBFB-MYH11–positive AML who are at high risk of relapse. Monitoring of CBFB-MYH11 transcript levels should be incorporated into future clinical trials to guide therapeutic decisions.

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.

Minimal Residual Disease in Patients with Acute Myeloid Leukemia Quantified by Multiparameter Flow Cytomety and Quantitative RT-PCR Is an Independent Prognostic Parameter.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 319-319 ◽  
Author(s):  
Wolfgang Kern ◽  
Claudia Schoch ◽  
Torsten Haferlach ◽  
Daniela Voskova ◽  
Wolfgang Hiddemann ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Minimal Residual Disease ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Prognostic Impact ◽  
Cox Regression Analysis ◽  
Minimal Residual ◽  
Acute Myeloid

Quantification of minimal residual disease (MRD) is becoming increasingly important to guide therapy in patients with acute myeloid leukemia (AML). While MFC can be applied to more patients with AML than QPCR, the latter has the advantage of a higher sensitivity in many cases. We compared data obtained by both methods in parallel in bone marrow samples in 160 patients at diagnosis and at 469 follow-up checkpoints. MFC was applied at diagnosis with a comprehensive panel of antibodies to identify leukemia-associated aberrant immunophenotypes (LAIP) useful for MRD monitoring. QPCR targeted on the leukemia-specific fusion transcripts AML1-ETO, AML1-EVI1, CBFB-MYH11, MLL-AF10, MLL-AF6, MLL-AF9, MLL-ELL, MLL-ENL, and PML-RARA as well as overexpression of EVI1, length mutations of FLT3, and partial tandem duplications of MLL. In order to adjust for differences in the percentages of bone marrow cells covered by the respective LAIP by MFC at diagnosis and for the heterogeneity of transcript levels detected by QPCR at diagnosis, the logarithmic difference (LD) was calculated for each follow-up sample in comparison to the diagnostic sample. There was a significant correlation between MFC and QPCR with regard to the LD from diagnosis to follow-up checkpoint (r=0.645, p=0.000001). Concordant results with regard to negativity between QPCR (no signal) and MFC (<0.01% positive cells) was found in 301/469 (64.2%) samples (both methods positive, 270 (57.6%); both methods negative, 31 (6.6%)). In 44 samples (9.4%) QPCR detected positivity and MFC negativity while in 124 samples (26.4%) MFC detected positivity and QPCR negativity (sensitivity of QPCR was lower than 1:100,000 in some cases). In 133 patients clinical follow-up data was available allowing the analysis of the prognostic impact of MRD levels. Cytogenetics were favorable, intermediate, and unfavorable in 86, 30, and 17 cases, respectively. Median age was 46 years (range, 17–83). Median event-free survival (EFS) was 22.1 months, overall survival (OS) at three years was 77%. The median LDs for MFC and QPCR at the checkpoint 1 (up to day 21), 2 (day 22–60), 3 (day 61–120), 4 (day 121–365), and 5 (after day 365) were 2.40 and 0.62, 2.05 and 1.55, 2.51 and 3.34, 2.71 and 3.70, and 2.60 and 3.45, respectively. Separating patients according to these median LDs resulted in a better EFS and OS for cases with higher LDs at all five checkpoints for each method. Significant differences in EFS were observed at checkpoints 2 (MFC, 22.1 vs. 12.6 months, p=0.0379; QPCR, median not reached vs. 9.9, p=0.0081), 3 (QPCR, 30.9 vs. 14.1 months, p=0.0011), 4 (MFC, median not reached vs. 16.9 months, p=0.0007; QPCR, median not reached vs. 15.1 months, p=0.0102), and 5 (QPCR, median not reached vs. 17.2, p=0.0008). Cox regression analysis taking into consideration cytogenetics, age, WBC count, and bone marrow blast count at diagnosis identified the LD at checkpoint 4 determined by MFC and the LD at checkpoints 2 and 5 determined by QPCR as independent prognostic factors. The results of our analyses confirm that both MFC and QPCR are highly sensitive methods capable of quantifying MRD in AML. While data are concordant for both methods in many cases, either of the two has advantages in distinct cases depending on the individual MRD marker. Clinical trials should consider MRD monitoring by both methods in order to prove their respective roles in risk prediction and treatment stratification.

Allogeneic Hematopoietic Stem Cell Transplantation Overcomes the Adverse Prognostic Impact of Minimal Residual Disease in Acute Myeloid Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2027-2027
Author(s):  
Betul Oran ◽  
Timothy Singleton ◽  
Pablo A. Ramirez ◽  
Ryan Shanley ◽  
Claudio Brunstein ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Minimal Residual Disease ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Prognostic Impact ◽  
Hematopoietic Stem ◽  
Disease Outcomes ◽  
The Impact ◽  
Minimal Residual ◽  
Acute Myeloid

Abstract Abstract 2027 BACKGROUND: The identification of minimal residual disease (MRD) can predict impending relapse in acute myeloid leukemia (AML) patients. Little data exists evaluating the prognostic impact of MRD, as determined by multiparametric flow cytometry (MFC), at the time of allogeneic (allo-HCT). Although disease outcomes may be worse for MRD positive (MRD+) patients, MRD is often associated with other adverse risk factors leaving it unclear whether MRD is an independent risk factor for relapse or a surrogate marker for underlying poor risk disease features. METHODS: We retrospectively analyzed 97 consecutive AML patients in complete morphological remission (CR) who underwent allo-HCT with a matched related donor (MRD, n=30, 31%), matched unrelated donor (MUD, n=4, 4%) or umbilical cord blood (UCB, n=63, 65%) at the University of Minnesota between January 2005 and June 2009. Presence of MRD at allo-HCT was determined by MFC. Analyses were done separately for myeloablative (MAC) and reduced intensity conditioning (RIC) patients, testing the impact of MRD along with conditioning intensity, age, donor type and disease status on allo-HCT outcomes. RESULTS: Of 97 patients, 41 (42%) had MAC; 57 (58%) had RIC. Sixty-six were in first CR (CR1) with the rest in CR2 or later remission (CR2+). MRD at allo-HCT was detected in 7 patients after MAC (17%) and 7 after RIC (12.5%); and this frequency was similar in patients in CR1 and CR2+ (13% vs. 16%, p=0.7). MRD+ and MRD- patients had similar median age (40 vs. 44 yrs), gender, donor source (MSD or MUD vs. UCB), CMV serostatus and diagnostic cytogenetic risk group. Six of 40 (15%) intermediate and 5 of 39 (13%) high risk cytogenetics patients had MRD+ (p=0.8). Only 3 of 53 patients with a cytogenetic abnormality at diagnosis had it detected prior allo-HCT and 1 of 3 had MRD. The median follow-up of survivors was 25 months. Two-year probabilities for MAC and RIC patients were similar: Overall survival (OS), 48% and 47 % and leukemia free survival (LFS) 43% and 41% respectively. When disease outcomes were analyzed separately by MRD status (table), OS and LFS were markedly worse in MRD+ patients receiving RIC, but this difference was not statistically significant. In multivariate analysis, MRD+ was not an independent prognostic factor for OS and LFS. Although we identified no adverse prognostic factors for MAC patients, patient with RIC in CR2+ had worse OS and LFS vs. CR1 (HR 2.6, p=0.04 and HR 2.7, p=0.04 respectively). CONCLUSION: The negative prognostic impact of MRD was overcome by allo-HCT with MAC, but outcomes with MRD+ were suggestively inferior after RIC. However due to limited sample size, MRD in patients with RIC should be further investigated. Disclosures: Weisdorf: Genzyme: Consultancy, Research Funding.

Relation of Clinical Response and Minimal Residual Disease and Their Prognostic Impact on Outcome in Acute Myeloid Leukemia

2015 ◽  
Vol 33 (11) ◽  
pp. 1258-1264 ◽  
Author(s):  
Xueyan Chen ◽  
Hu Xie ◽  
Brent L. Wood ◽  
Roland B. Walter ◽  
John M. Pagel ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Minimal Residual Disease ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Blood Count ◽  
Residual Disease ◽  
Prognostic Impact ◽  
Minimal Residual ◽  
Acute Myeloid ◽  
Count Recovery

Purpose Both presence of minimal residual disease (MRD) and achievement of complete remission (CR) with incomplete platelet recovery (CRp) rather than CR after induction therapy predict relapse in acute myeloid leukemia (AML). These results suggest a correlation between response (peripheral count recovery) and MRD at the time of morphologic remission. Here we examine this hypothesis and whether MRD and response provide independent prognostic information after accounting for other relevant covariates. Patients and Methods We retrospectively analyzed data from 245 adults with AML who achieved CR, CRp, or CR with incomplete blood count recovery (CRi) after induction therapy. Bone marrow samples were collected on or closest to the first date of blood count recovery, and MRD was determined by 10-color multiparameter flow cytometry. Results The 71.0% of patients who achieved CR had MRD less frequently and had lower levels of MRD than the 19.6% of patients achieving CRp and 9.4% achieving CRi. Although pretreatment covariates such as cytogenetics, monosomal karyotype, relapsed or refractory rather than newly diagnosed AML, and FLT3 internal tandem duplication were associated with relapse, their prognostic effect was much lower once MRD and response were taken into account, the univariable statistical effect of which was not materially affected by inclusion of pretreatment covariates. Conclusion Our data indicate that post-therapy parameters including MRD status and response are important independent prognostic factors for outcome in patients with AML achieving remission. MRD status and type of response (CR v CRp or CRi) should play important, and perhaps dominant, roles in planning postinduction therapy.

scholarly journals High Prognostic Impact of Flow Cytometric Minimal Residual Disease Detection in Acute Myeloid Leukemia: Data From the HOVON/SAKK AML 42A Study

2013 ◽  
Vol 31 (31) ◽  
pp. 3889-3897 ◽  
Author(s):  
Monique Terwijn ◽  
Wim L.J. van Putten ◽  
Angèle Kelder ◽  
Vincent H.J. van der Velden ◽  
Rik A. Brooimans ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factor ◽  
Minimal Residual Disease ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Prognostic Impact ◽  
Consolidation Treatment ◽  
Leukemia Data ◽  
Minimal Residual ◽  
Acute Myeloid

Purpose Half the patients with acute myeloid leukemia (AML) who achieve complete remission (CR), ultimately relapse. Residual treatment-surviving leukemia is considered responsible for the outgrowth of AML. In many retrospective studies, detection of minimal residual disease (MRD) has been shown to enable identification of these poor-outcome patients by showing its independent prognostic impact. Most studies focus on molecular markers or analyze data in retrospect. This study establishes the value of immunophenotypically assessed MRD in the context of a multicenter clinical trial in adult AML with sample collection and analysis performed in a few specialized centers. Patients and Methods In adults (younger than age 60 years) with AML enrolled onto the Dutch-Belgian Hemato-Oncology Cooperative Group/Swiss Group for Clinical Cancer Research Acute Myeloid Leukemia 42A study, MRD was evaluated in bone marrow samples in CR (164 after induction cycle 1, 183 after cycle 2, 124 after consolidation therapy). Results After all courses of therapy, low MRD values distinguished patients with relatively favorable outcome from those with high relapse rate and adverse relapse-free and overall survival. In the whole patient group and in the subgroup with intermediate-risk cytogenetics, MRD was an independent prognostic factor. Multivariate analysis after cycle 2, when decisions about consolidation treatment have to be made, confirmed that high MRD values (> 0.1% of WBC) were associated with a higher risk of relapse after adjustment for consolidation treatment time-dependent covariate risk score and early or later CR. Conclusion In future treatment studies, risk stratification should be based not only on risk estimation assessed at diagnosis but also on MRD as a therapy-dependent prognostic factor.

Multivariate Analysis of Prognostic Impact of Flow Cytometrically Determined Minimal Residual Disease in Patients with Acute Myeloid Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2371-2371
Author(s):  
Wolfgang Kern ◽  
Daniela Voskova ◽  
Claudia Schoch ◽  
Susanne Schnittger ◽  
Torsten Haferlach
Keyword(s):  
Flow Cytometry ◽  
Acute Myeloid Leukemia ◽  
Multivariate Analysis ◽  
Minimal Residual Disease ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Multiparameter Flow Cytometry ◽  
Prognostic Impact ◽  
Minimal Residual ◽  
Acute Myeloid

Abstract Treatment of acute myeloid leukemia (AML) is adapted according to individual risk profiles. The assessment of levels of minimal residual disease (MRD) is feasible in the vast majority of patients with AML and may significantly improve prognostication. We applied multiparameter flow cytometry to highly sensitively quantify MRD in patients with AML and analyzed its prognostic impact in a multivariate analysis. A total of 356 patients receiving standardized intensive antileukemic treatment was analyzed at different checkpoints: CP1 (up to day 28, n=156), CP2 (day 28–60, n=122), CP3 (day 61–120, n=195), CP4 (day 121–365, n=172), and CP5 (after day 365, n=73). Leukemic cells were identified by their individually defined leukemia-associated aberrant immunophenotypes (LAIPs). MRD levels were calculated as the logarithmic difference (LD) between LAIP-positive cells at diagnosis and LAIP-positive cells at follow-up assessment. The median LD amounted to 2.18 (range, −0.14 to 4.20) at CP1, 2.31 (−0.03 to 4.17) at CP2, 2.49 (0.11 to 4.17) at CP3, 2.58 (−0.28 to 4.28) at CP4, and 2.87 (0.46 to 4.02) at CP5. A higher LD (continuous variable) was related to a better event-free survival (EFS; CP1, p=0.0002; CP2, p=0.00001; CP3, p=0.0002; CP4, p&lt;0.00001; CP5, p=0.00007) and to a better overall survival (OS; CP1, p=0.004; CP2, p=0.001; CP3, p=0.021; CP4, p=0.00006). Other parameters related to EFS and OS were age and cytogenetics in the present series. The prognostic impact of MRD levels on outcome was idependent of cytogenetics and age for EFS (CP2 to CP5) and OS (CP2 and CP4). MRD was the most important prognostic parameter at CP4 and CP5. Separation of patients into two groups, respectively, by the median LD resulted in significant differences in EFS at all CPs and in OS at CP1 to CP4. The largest difference was observed at CP4: median EFS, 57.1 vs. 13.7 months, p&lt;0.00001; 3-year-OS, 95% vs. 65%, p=0.0003. Determination of MRD levels by multiparameter flow cytometry provides a highly powerful and independent prognostic parameter which is applicable to the total of an AML population. It should be evaluated as a stratification parameter in clinical trials.

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