Activity of decitabine as maintenance therapy in core binding factor acute myeloid leukemia.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 7522-7522
Author(s):  
Mahran Shoukier ◽  
Hagop M. Kantarjian ◽  
Guillermo Garcia-Manero ◽  
Keyur P. Patel ◽  
Tapan M. Kadia ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Maintenance Therapy ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Cell Transplant ◽  
Core Binding Factor ◽  
Binding Factor ◽  
Group 2 ◽  
Acute Myeloid ◽  
Group 1

7522 Background: Real-time quantitative (RTPCR) based minimal residual disease (MRD) monitoring provides prognostic information in core binding factor acute myeloid leukemia (CBF-AML). Earlier we reported on the activity of decitabine (DAC) as maintenance therapy in a smaller cohort of patients with CBF AML. Methods: We have summarized the results in patients (pts) with CBF who received DAC maintenance for persistent RTPCR positivity or because of inability to complete all planned consolidation in a fludarabine, GCSF, cytarabine (FLAG) based regimen. The planned number of DAC cycles was 12 but could be adjusted at the discretion of the treating physician based on RTPCR response. Serial RTPCR was obtained approximately every 2-3 months. Results: Thirty-four pts with CBF-AML [t(8;21)=14 and inv(16)=20] received DAC as maintenance. Eighteen pts (53%) completed a full course (7 cycles) of FLAG based regimen before DAC for persistent PCR positivity (group 1). Sixteen pts (47%) were switched to DAC as they did not complete planned consolidation (group 2). In group 2, 9 pts (56%) had negative PCR (group 2A) and 7 pts (46%) had positive PCR (group 2B) prior to starting DAC. Patient characteristics are summarized in table. The median follow up was 59.2 [15.4-107.2] and 32.47 [8.5-86.3] months for group 1 and 2, respectively. In Group 1 and group 2A only 1 patient each had relapse, while 5 pts (72%) from group 2B had relapse. All the patients in group 2B with relapse were at suboptimal RTPCR response (>0.1%). Conclusions: Our study shows DAC is an effective maintenance for CBF-AML pts who have persistent PCR positively after FLAG based induction consolidation and those unable to tolerate a full course, but have negative PCR. However patients with high levels of MRD persistence should be considered for stem cell transplant. [Table: see text]

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

scholarly journals Measurable residual disease monitoring provides insufficient lead-time to prevent morphologic relapse in the majority of patients with core-binding factor acute myeloid leukemia

Haematologica ◽  
2020 ◽  
Vol 106 (1) ◽  
pp. 56-63 ◽  
Author(s):  
Robert Puckrin ◽  
Eshetu G. Atenafu ◽  
Jaime O. Claudio ◽  
Steven Chan ◽  
Vikas Gupta ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Lead Time ◽  
Residual Disease ◽  
Molecular Monitoring ◽  
Core Binding Factor ◽  
Log Reduction ◽  
Binding Factor ◽  
Measurable Residual Disease ◽  
Acute Myeloid

Core-binding factor acute myeloid leukemia is characterized by t(8;21) or inv(16) and the fusion proteins RUNX1-RUNX1T1 and CBFB-MYH11. International guidelines recommend monitoring for measurable residual disease every 3 months for 2 years after treatment. However, it is unknown if serial molecular monitoring can predict and prevent morphologic relapse. We conducted a retrospective single-center study of 114 patients in complete remission who underwent molecular monitoring with RT-qPCR of RUNX1-RUNX1T1 or CBFB-MYH11 transcripts every 3 months. Morphologic relapse was defined as re-emergence of >5% blasts and molecular relapse as ≥1 log increase in transcript level between 2 samples. Over a median follow-up time of 3.7 years (range 0.2-14.3), remission persisted in 71 (62.3%) patients but 43 (37.7%) developed molecular or morphologic relapse. Patients who achieved <3 log reduction in RUNX1-RUNX1T1 or CBFB-MYH11 transcripts at end of chemotherapy had a significantly higher risk of relapse compared to patients who achieved ≥3 log reduction (61.1% vs. 33.7%, p=0.004). The majority of relapses (74.4%, n=32) were not predicted by molecular monitoring and occurred rapidly with <100 days from molecular to morphologic relapse. Molecular monitoring enabled the detection of impending relapse and permitted pre-emptive intervention prior to morphologic relapse in only 11 (25.6%) patients. The current practice of molecular monitoring every 3 months provided insufficient lead-time to identify molecular relapses and prevent morphologic relapse in the majority of patients with core-binding factor acute myeloid leukemia treated at our institution. Further research is necessary to determine the optimal monitoring strategies for these patients.

Predictive value of molecular remissions postconsolidation chemotherapy in patients with Core Binding Factor Acute Myeloid Leukemia (CBF-AML) - a single center analysis

2016 ◽  
Vol 35 (4) ◽  
pp. 810-813 ◽  
Author(s):  
Uday Deotare ◽  
Marwan Shaheen ◽  
Joseph M. Brandwein ◽  
Bethany Pitcher ◽  
Suzanne Kamel-Reid ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Predictive Value ◽  
Myeloid Leukemia ◽  
Single Center ◽  
Core Binding Factor ◽  
Binding Factor ◽  
Acute Myeloid

scholarly journals Population-based disparities in survival among patients with core-binding factor acute myeloid leukemia: A SEER database analysis

2014 ◽  
Vol 38 (7) ◽  
pp. 773-780 ◽  
Author(s):  
Andrew M. Brunner ◽  
Traci M. Blonquist ◽  
Hossein Sadrzadeh ◽  
Ashley M. Perry ◽  
Eyal C. Attar ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Population Based ◽  
Seer Database ◽  
Database Analysis ◽  
Core Binding Factor ◽  
Binding Factor ◽  
Acute Myeloid

scholarly journals A Predictor Combining Clinical and Genetic Factors for AML1-ETO Leukemia Patients

2022 ◽  
Vol 11 ◽  
Author(s):  
Min Yang ◽  
Bide Zhao ◽  
Jinghan Wang ◽  
Yi Zhang ◽  
Chao Hu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Somatic Mutations ◽  
Genetic Factors ◽  
Risk Model ◽  
Core Binding Factor ◽  
Kit Mutation ◽  
Binding Factor ◽  
Prognostic Prediction ◽  
Acute Myeloid

Core Binding Factor (CBF)-AML is one of the most common somatic mutations in acute myeloid leukemia (AML). t(8;21)/AML1-ETO-positive acute myeloid leukemia accounts for 5-10% of all AMLs. In this study, we consecutively included 254 AML1-ETO patients diagnosed and treated at our institute from December 2009 to March 2020, and evaluated molecular mutations by 185-gene NGS platform to explore genetic co-occurrences with clinical outcomes. Our results showed that high KIT VAF(≥15%) correlated with shortened overall survival compared to other cases with no KIT mutation (3-year OS rate 26.6% vs 59.0% vs 69.6%, HR 1.50, 95%CI 0.78-2.89, P=0.0005). However, no difference was found in patients’ OS whether they have KIT mutation in two or three sites. Additionally, we constructed a risk model by combining clinical and molecular factors; this model was validated in other independent cohorts. In summary, our study showed that c-kit other than any other mutations would influence the OS in AML1-ETO patients. A proposed predictor combining both clinical and genetic factors is applicable to prognostic prediction in AML1-ETO patients.

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