How Precision Medicine Is Changing Acute Myeloid Leukemia Therapy

2019 ◽  
pp. 411-420 ◽  
Author(s):  
Michael Heuser ◽  
Alain Mina ◽  
Eytan M. Stein ◽  
Jessica K. Altman
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Treatment Decision ◽  
Response Assessment ◽  
Response To Treatment ◽  
Multiparameter Flow Cytometry ◽  
Treatment Decision Making ◽  
Prognostic Assessment ◽  
Acute Myeloid

Pretreatment somatic mutations influence acute myeloid leukemia (AML) pathogenesis and responses to chemotherapy. Integration of cytogenetic abnormalities and molecular mutations, co-occurring and in isolation, have resulted in a more refined prognostic assessment. In addition, research performed over the last few years has led to the development of novel therapies and new drug approvals in patients with both newly diagnosed and relapsed/refractory (R/R) AML. Here we discuss the use of these newly approved therapies. Advances in AML have also occurred through development of better tools to assess response to treatment. Both multiparameter flow cytometry and polymerase chain reaction can be used to assess for the presence or absence of measurable residual disease (MRD) and increase the sensitivity of response assessment. The role of MRD assessment is gaining relevance and its integration in clinical trials and treatment decision making will be explored in the second half of this article.

AMELIORATE: early intensification in FLT3-mutated acute myeloid leukemia based on peripheral blast clearance – MYNERVA-GIMEMA AML1919 trial

2021 ◽  
Author(s):  
Francesco Mannelli ◽  
Giacomo Gianfaldoni ◽  
Paola Guglielmelli ◽  
Francesco Buccisano ◽  
Roberto Caporale ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Disease Status ◽  
Phase Iii ◽  
Multiparameter Flow Cytometry ◽  
Current Standard ◽  
Disease Category ◽  
Measurable Residual Disease ◽  
Acute Myeloid

AMELIORATE is a Phase III, randomized trial aiming to personalize treatment intensity in FLT3-mutated acute myeloid leukemia. The current study provides an early appraisal of chemosensitivity based on peripheral blasts clearance, as assessed by multiparameter flow cytometry, from baseline to day 4 of induction. This biomarker was previously demonstrated to predict complete remission achievement and measurable residual disease status. For patients experiencing low peripheral blast cells (i.e., ≤2.0 logs), two major adjustments of treatment as compared with current standard of care are envisioned in the experimental arm: the immediate switch to intensified induction with high-doses cytarabine (1500 mg/m2 b.i.d. on days 5–7 of induction); and the early allocation of the patient to high-risk disease category, to be further refined later based on postinduction measurable residual disease status.

Effect of Age on Treatment Decision-Making in Elderly Patients With Acute Myeloid Leukemia

2015 ◽  
Vol 15 (8) ◽  
pp. 477-483 ◽  
Author(s):  
Jihane Fattoum ◽  
Giovanna Cannas ◽  
Mohamed Elhamri ◽  
Isabelle Tigaud ◽  
Adriana Plesa ◽  
...  
Keyword(s):  
Decision Making ◽  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Myeloid Leukemia ◽  
Treatment Decision ◽  
Treatment Decision Making ◽  
Effect Of Age ◽  
Acute Myeloid

scholarly journals Measurable Residual Disease Detected by Multiparameter Flow Cytometry and Sequencing Improves Prediction of Relapse and Survival in Acute Myeloid Leukemia

2021 ◽  
Vol 11 ◽  
Author(s):  
Fu-Jia Liu ◽  
Wen-Yan Cheng ◽  
Xiao-Jing Lin ◽  
Shi-Yang Wang ◽  
Tian-Yi Jiang ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Prognostic Significance ◽  
Multiparameter Flow Cytometry ◽  
Net Reclassification Improvement ◽  
Measurable Residual Disease ◽  
Acute Myeloid ◽  
Time Point

The clinically ideal time point and optimal approach for the assessment of measurable residual disease (MRD) in patients with acute myeloid leukemia (AML) are still inconclusive. We investigated the clinical value of multiparameter flow cytometry-based MRD (MFC MRD) after induction (n = 492) and two cycles of consolidation (n = 421). The latter time point was proved as a superior indicator with independent prognostic significance for both relapse-free survival (RFS, HR = 3.635, 95% CI: 2.433–5.431, P <0.001) and overall survival (OS: HR = 3.511, 95% CI: 2.191–5.626, P <0.001). Furthermore, several representative molecular MRD markers were compared with the MFC MRD. Both approaches can establish prognostic value in patients with NPM1 mutations, and FLT3, C-KIT, or N-RAS mutations involved in kinase-related signaling pathways, while the combination of both techniques further refined the risk stratification. The detection of RUNX1–RUNX1T1 fusion transcripts achieved a considerable net reclassification improvement in predicting the prognosis. Conversely, for patients with biallelic CEBPA or DNMT3A mutations, only the MFC method was recommended due to the poor prognostic discriminability in tracking mutant transcripts. In conclusion, this study demonstrated that the MFC MRD after two consolidation cycles independently predicted clinical outcomes, and the integration of MFC and molecular MRD should depend on different types of AML-related genetic lesions.

Defining minimal residual disease in acute myeloid leukemia: which platforms are ready for “prime time”?

Blood ◽  
2014 ◽  
Vol 124 (23) ◽  
pp. 3345-3355 ◽  
Author(s):  
David Grimwade ◽  
Sylvie D. Freeman
Keyword(s):  
Acute Myeloid Leukemia ◽  
Minimal Residual Disease ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Multiparameter Flow Cytometry ◽  
Molecular Heterogeneity ◽  
Prognostic Information ◽  
Reliable Determination ◽  
Minimal Residual ◽  
Acute Myeloid

Abstract The past 40 years have witnessed major advances in defining the cytogenetic aberrations, mutational landscape, epigenetic profiles, and expression changes underlying hematological malignancies. Although it has become apparent that acute myeloid leukemia (AML) is highly heterogeneous at the molecular level, the standard framework for risk stratification guiding transplant practice in this disease remains largely based on pretreatment assessment of cytogenetics and a limited panel of molecular genetic markers, coupled with morphological assessment of bone marrow (BM) blast percentage after induction. However, application of more objective methodology such as multiparameter flow cytometry (MFC) has highlighted the limitations of morphology for reliable determination of remission status. Moreover, there is a growing body of evidence that detection of subclinical levels of leukemia (ie, minimal residual disease, MRD) using MFC or molecular-based approaches provides powerful independent prognostic information. Consequently, there is increasing interest in the use of MRD detection to provide early end points in clinical trials and to inform patient management. However, implementation of MRD assessment into clinical practice remains a major challenge, hampered by differences in the assays and preferred analytical methods employed between routine laboratories. Although this should be addressed through adoption of standardized assays with external quality control, it is clear that the molecular heterogeneity of AML coupled with increasing understanding of its clonal architecture dictates that a “one size fits all” approach to MRD detection in this disease is not feasible. However, with the range of platforms now available, there is considerable scope to realistically track treatment response in every patient.

Patient experiences of acute myeloid leukemia: A qualitative study about diagnosis, illness understanding, and treatment decision-making

2016 ◽  
Vol 26 (12) ◽  
pp. 2063-2068 ◽  
Author(s):  
Thomas W. LeBlanc ◽  
Laura J. Fish ◽  
Catherine T. Bloom ◽  
Areej El-Jawahri ◽  
Debra M. Davis ◽  
...  
Keyword(s):  
Decision Making ◽  
Acute Myeloid Leukemia ◽  
Qualitative Study ◽  
Myeloid Leukemia ◽  
Treatment Decision ◽  
Patient Experiences ◽  
Treatment Decision Making ◽  
Acute Myeloid
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