Core binding factor acute myeloid leukemia: the impact of age, leukocyte count, molecular findings, and minimal residual disease

2013 ◽  
Vol 91 (3) ◽  
pp. 209-218 ◽  
Author(s):  
Montserrat Hoyos ◽  
Josep F. Nomdedeu ◽  
Jordi Esteve ◽  
Rafael Duarte ◽  
Josep M. Ribera ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Minimal Residual Disease ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Leukocyte Count ◽  
Core Binding Factor ◽  
Binding Factor ◽  
The Impact ◽  
Minimal Residual ◽  
Acute Myeloid

scholarly journals Minimal residual disease eradication with epigenetic therapy in core binding factor acute myeloid leukemia

2017 ◽  
Vol 92 (9) ◽  
pp. 845-850 ◽  
Author(s):  
Brittany Knick Ragon ◽  
Naval Daver ◽  
Guillermo Garcia-Manero ◽  
Farhad Ravandi ◽  
Jorge Cortes ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Minimal Residual Disease ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Epigenetic Therapy ◽  
Core Binding Factor ◽  
Disease Eradication ◽  
Binding Factor ◽  
Minimal Residual ◽  
Acute Myeloid

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.

scholarly journals Can Minimal Residual Disease Determination in Acute Myeloid Leukemia Be Used in Clinical Practice?

2017 ◽  
Vol 13 (8) ◽  
pp. 471-480 ◽  
Author(s):  
Marlise R. Luskin ◽  
Richard M. Stone
Keyword(s):  
Acute Myeloid Leukemia ◽  
Clinical Practice ◽  
Minimal Residual Disease ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Multiparameter Flow Cytometry ◽  
Term Survival ◽  
The Impact ◽  
Minimal Residual ◽  
Acute Myeloid

In acute myeloid leukemia (AML) that is in complete remission, minimal residual disease (MRD) is presumed to be present, though not morphologically evident. Advances in diagnostics now permit the detection and quantification of MRD in AML by several techniques. The level of MRD after induction and consolidation therapy correlates with disease sensitivity to chemotherapy and has greater power to predict long-term survival than patient and disease characteristics that are available at diagnosis, including genetic information. A unique advantage of MRD is that it is an integrated measure of the impact and interaction of genetics, epigenetics, host immune milieu, bone marrow environment, and drug sensitivity on disease response to treatment. Here, we review the main techniques for MRD assessment in AML, including polymerase chain reaction, multiparameter flow cytometry, and next-generation sequencing, with a focus on method-specific and general limitations to the optimal employment of MRD techniques for the determination of AML prognosis. We also review the data that establish the prognostic and predictive value of MRD assessment in AML. Finally, we provide recommendations for the use of MRD in the care of patients with AML in clinical practice today, including whether it should influence treatment decisions.

Core Binding Factor Acute Myeloid Leukemia In Pediatric Patients Enrolled In The AIEOP AML 2002/01 Trial: The Impact Of Minimal Residual Disease On Patient Outcome

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3884-3884
Author(s):  
Martina Pigazzi ◽  
Valzerda Beqiri ◽  
Elena Manara ◽  
Roberto Rondelli ◽  
Riccardo Masetti ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Minimal Residual Disease ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Prognostic Impact ◽  
Rt Pcr ◽  
The Impact ◽  
Minimal Residual ◽  
Acute Myeloid

Abstract Introduction Acute Myeloid Leukemia (AML) accounts for 15% of pediatric leukemia. Improvements of prognosis achieved in the last twenty years are also due to a better stratification of patients into risk groups that allowed to deliver tailored treatment. The AIEOP LAM 2002/01 protocol classified patients with t(8;21)(q22,q22)AML1-ETO and inv(16)(p13;q22)CBFB-MYH11, who responded to induction therapy as belonging to the Standard-Risk (SR) group. These patients were considered at good prognosis; unfortunately, although they all reached morphological complete remission (CR) after the first induction course, they showed a high incidence of relapse (24%) (Pession A. et al., Blood 2013). At present, little is known about the kinetics of relapse or the development of resistance mechanisms; moreover, in many studies post-remission therapy in AML does not take into account the level of residual leukemia. Here, we evaluate the prognostic impact of molecular minimal residual disease (MRD) levels in terms of onset of relapse. Methods We studied bone marrow of 49 and 30 patients carrying either t(8;21) or inv(16) abnormalities, respectively, at time of diagnosis, and at the end of first and second course of induction therapy (ICE: Idarubicine, Citarabine and Etoposide). MRD was evaluated as number of fusion transcripts by quantitative RT-PCR using absolute quantification, and calculated as logarithmic (Log) disease reduction after the first and second ICE course as compared to diagnosis. Fusion transcripts were normalized to 10(5) ABL copies. The prognostic impact was assessed by the calculation of Overall Survival (OS) and cumulative incidence of relapse (CIR) according to the different MRD levels. Results After I ICE, t(8;21)-rearranged patients distributed equally in the four classes of MRD reduction. In particular, 10 patients reduced MRD levels of less than 1 Log, 11 patients reduced 1-2 Log, 17 patients reduced 2-3 Log and 11 patients reduced MRD levels of more than 3 Log as compared to diagnosis. After II ICE, the majority of patients increased the reduction of MRD levels (> 3 Log). We focused on the 10 patients who did not respond to the I ICE course and we found that 7 out of 10 reduced MRD levels of more than 1 Log after the II ICE, confirming a slow clearance of blasts for this subgroup of patients. We found that a reduction of MRD lower than 1 Log conferred a worst outcome to t(8;21)-rearranged patients (OS being 53.3% vs 85.2%, p=0.073 after I ICE; 33.3% vs 82.4 p= 0.062 after II ICE), and higher CIR after I and II ICE (52% vs 12.3%, p=0.0049, and 66.7 %, vs 17.2, p=0.024, at 6 years respectively). The group of inv(16)-rearranged achieved more than 1 Log reduction of MRD since I ICE course. After II ICE course, the majority of of patients reduced MRD of more than 3 Log, and 20% of them were completely negative. Inv(16) rearranged patients were all alive at last follow-up, and CIR never showed statistically significant differences for MRD levels in inv(16)-rearranged patients after the induction therapy. The impact of copy numbers (i.e. transcript levels) at diagnosis and after induction courses on relapse risk never showed significant results in both subgroups of CBF-rearranged patients. Conclusions Our data indicate that MRD evaluation using quantitative RT-PCR is an important diagnostic tool that permits the assessment of response to CT and the identification of patients at greater risk of relapse after induction therapy for AML1-ETO rearranged patients. We propose that at the end of induction therapy the cut-off of MRD< 1 Log be used to guide therapeutic decisions for this subgroup of SR patients. On the contrary, MRD levels of CBFB-MYH11 rearranged patients do not have prognostic value on CIR after induction therapy, this suggesting that novel molecular features should be investigated for this subgroup of AML. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document