Treatment Strategies for Therapy-related Acute Myeloid Leukemia

2020 ◽  
Vol 20 (3) ◽  
pp. 147-155 ◽  
Author(s):  
Prajwal Dhakal ◽  
Bimatshu Pyakuryal ◽  
Prasun Pudasainee ◽  
Venkat Rajasurya ◽  
Krishna Gundabolu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Treatment Strategies ◽  
Acute Myeloid

scholarly journals Acute Myeloid Leukemia and Acute Promyelocytic Leukemia

Hematology ◽  
2003 ◽  
Vol 2003 (1) ◽  
pp. 82-101 ◽  
Author(s):  
Bob Löwenberg ◽  
James D. Griffin ◽  
Martin S. Tallman
Keyword(s):  
Acute Myeloid Leukemia ◽  
Acute Promyelocytic Leukemia ◽  
Tyrosine Kinases ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Treatment Strategies ◽  
Promyelocytic Leukemia ◽  
Remission Induction ◽  
Novel Drugs ◽  
Acute Myeloid

Abstract The therapeutic approach to the patient with acute myeloid leukemia (AML) currently evolves toward new frontiers. This is particularly apparent from the entree of high-throughput diagnostic technologies and the identification of prognostic and therapeutic targets, the introduction of therapies in genetically defined subgroups of AML, as well as the influx of investigational approaches and novel drugs into the pipeline of clinical trials that target pathogenetic mechanisms of the disease. In Section I, Dr. Bob Löwenberg reviews current issues in the clinical practice of the management of adults with AML, including those of older age. Dr. Löwenberg describes upcoming possibilities for predicting prognosis in defined subsets by molecular markers and reviews experimental strategies to improve remission induction and postinduction treatment. In Section II, Dr. James Griffin reviews the mechanisms that lead to activation of tyrosine kinases by mutations in AML, the consequences of that activation for the cell, and the opportunities for targeted therapy and discusses some examples of developing novel drugs (tyrosine kinase inhibitors) and their effectiveness in AML (FLT3). In Section III, Dr. Martin Tallman describes the evaluation and management of patients with acute promyelocytic leukemia, a notable example of therapeutic progress in a molecularly defined entity of leukemia. Dr. Tallman focuses on the molecular genetics of APL, current curative treatment strategies and approaches for patients with relapsed and refractory disease. In addition, areas of controversy regarding treatment are addressed.

scholarly journals Use of carbapenems and glycopeptides increases risk for Clostridioides difficile infections in acute myeloid leukemia patients undergoing intensive induction chemotherapy

2020 ◽  
Vol 99 (11) ◽  
pp. 2547-2553
Author(s):  
Olivier Ballo ◽  
Eva-Maria Kreisel ◽  
Fagr Eladly ◽  
Uta Brunnberg ◽  
Jan Stratmann ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Bacterial Infections ◽  
Treatment Strategies ◽  
Length Of Hospital Stay ◽  
Infectious Complications ◽  
Clostridioides Difficile ◽  
Acute Myeloid

Abstract Patients with acute myeloid leukemia (AML) are often exposed to broad-spectrum antibiotics and thus at high risk of Clostridioides difficile infections (CDI). As bacterial infections are a common cause for treatment-related mortality in these patients, we conducted a retrospective study to analyze the incidence of CDI and to evaluate risk factors for CDI in a large uniformly treated AML cohort. A total of 415 AML patients undergoing intensive induction chemotherapy between 2007 and 2019 were included in this retrospective analysis. Patients presenting with diarrhea and positive stool testing for toxin-producing Clostridioides difficile were defined to have CDI. CDI was diagnosed in 37 (8.9%) of 415 AML patients with decreasing CDI rates between 2013 and 2019 versus 2007 to 2012. Days with fever, exposition to carbapenems, and glycopeptides were significantly associated with CDI in AML patients. Clinical endpoints such as length of hospital stay, admission to ICU, response rates, and survival were not adversely affected. We identified febrile episodes and exposition to carbapenems and glycopeptides as risk factors for CDI in AML patients undergoing induction chemotherapy, thereby highlighting the importance of interdisciplinary antibiotic stewardship programs guiding treatment strategies in AML patients with infectious complications to carefully balance risks and benefits of anti-infective agents.

scholarly journals New Targeted Agents in Acute Myeloid Leukemia: New Hope on the Rise

2019 ◽  
Vol 20 (8) ◽  
pp. 1983 ◽  
Author(s):  
Stephan R. Bohl ◽  
Lars Bullinger ◽  
Frank G. Rücker
Keyword(s):  
Acute Myeloid Leukemia ◽  
Patient Outcomes ◽  
Myeloid Leukemia ◽  
Treatment Strategies ◽  
Gemtuzumab Ozogamicin ◽  
Molecular Heterogeneity ◽  
Targeted Agents ◽  
Fda Approval ◽  
Cytotoxic Treatment ◽  
Acute Myeloid

The therapeutic approach for acute myeloid leukemia (AML) remains challenging, since over the last four decades a stagnation in standard cytotoxic treatment has been observed. But within recent years, remarkable advances in the understanding of the molecular heterogeneity and complexity of this disease have led to the identification of novel therapeutic targets. In the last two years, seven new targeted agents (midostaurin, gilteritinib, enasidenib, ivosidenib, glasdegib, venetoclax and gemtuzumab ozogamicin) have received US Food and Drug Administration (FDA) approval for the treatment of AML. These drugs did not just prove to have a clinical benefit as single agents but have especially improved AML patient outcomes if they are combined with conventional therapy. In this review, we will focus on currently approved and promising upcoming agents and we will discuss controversial aspects and limitations of targeted treatment strategies.

scholarly journals The pan-Bcl-2 inhibitor obatoclax promotes differentiation and apoptosis of acute myeloid leukemia cells

2020 ◽  
Vol 38 (6) ◽  
pp. 1664-1676
Author(s):  
Małgorzata Opydo-Chanek ◽  
Iwona Cichoń ◽  
Agnieszka Rak ◽  
Elżbieta Kołaczkowska ◽  
Lidia Mazur
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Treatment Strategies ◽  
Leukemic Cell ◽  
Leukemic Cells ◽  
Dependent Manner ◽  
Apoptotic Pathway ◽  
Acute Myeloid Leukemia Cells ◽  
Induced Apoptosis ◽  
Acute Myeloid

Summary One of the key features of acute myeloid leukemia (AML) is the arrest of differentiation at the early progenitor stage of myelopoiesis. Therefore, the identification of new agents that could overcome this differentiation block and force leukemic cells to enter the apoptotic pathway is essential for the development of new treatment strategies in AML. Regarding this, herein we report the pro-differentiation activity of the pan-Bcl-2 inhibitor, obatoclax. Obatoclax promoted differentiation of human AML HL-60 cells and triggered their apoptosis in a dose- and time-dependent manner. Importantly, obatoclax-induced apoptosis was associated with leukemic cell differentiation. Moreover, decreased expression of Bcl-2 protein was observed in obatoclax-treated HL-60 cells. Furthermore, differentiation of these cells was accompanied by the loss of their proliferative capacity, as shown by G0/G1 cell cycle arrest. Taken together, these findings indicate that the anti-AML effects of obatoclax involve not only the induction of apoptosis but also differentiation of leukemic cells. Therefore, obatoclax represents a promising treatment for AML that warrants further exploration.

Genetic and immunophenotypical diagnostics for acute myeloid leukemia and their implication on treatment strategy

2012 ◽  
Vol 0 (0) ◽  
pp. -
Author(s):  
Sabine Kayser ◽  
Richard F. Schlenk
Keyword(s):  
Acute Myeloid Leukemia ◽  
Treatment Strategy ◽  
Myeloid Leukemia ◽  
Molecular Genetic ◽  
Treatment Strategies ◽  
Disease Classification ◽  
Novel Drugs ◽  
Genetic Abnormalities ◽  
Binding Factor ◽  
Acute Myeloid

AbstractCytogenetic and molecular genetic abnormalities in acute myeloid leukemia (AML) play an important role in the pathogenesis, are absolutely necessary for disease classification, are the most important prognostic factors for induction success and survival, and are increasingly used for specific genotype-adapted treatment approaches. In particular, molecular-targeted treatment strategies are evolving within clinical trials in the AML entities core-binding factor AML, characterized by t(8;21) and inv(16)/t(16;16), and AML with mutated NPM1, as well as AML with an internal tandem duplication of the FMS-related tyrosine kinase 3 (FLT3) gene. The link between the leukemogenic importance of genetic abnormalities and their role as a potential target for well-known and novel drugs will contribute to the stepwise replacement of purely risk-adapted therapy to a more and more genotype-adapted treatment strategy.

Similar outcome of different treatment strategies in patients 16 to 60 years of age with acute myeloid leukemia (AML)

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 7080-7080
Author(s):  
T. Buchner ◽  
H. Dohner ◽  
G. Ehninger ◽  
A. Ganser ◽  
J. Hasford ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Treatment Strategies ◽  
Acute Myeloid

Age-Specific Differences in Oncogenic Pathway Dysregulation in Patients With Acute Myeloid Leukemia

2009 ◽  
Vol 27 (33) ◽  
pp. 5580-5586 ◽  
Author(s):  
Arati V. Rao ◽  
Peter J.M. Valk ◽  
Klaus H. Metzeler ◽  
Chaitanya R. Acharya ◽  
Sascha A. Tuchman ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Treatment Strategies ◽  
Gene Set Enrichment Analysis ◽  
Oncogenic Signaling ◽  
Younger Patients ◽  
Pathway Activation ◽  
Acute Myeloid

Purpose To define the biology driving the aggressive nature of acute myeloid leukemia (AML) in elderly patients. Patients and Methods Clinically annotated microarray data from 425 patients with newly diagnosed de novo AML from two publicly available data sets were analyzed after age-specific cohorts (young ≤ 45 years, n = 175; elderly ≥ 55 years; n = 144) were prospectively identified. Gene expression analysis was conducted utilizing gene set enrichment analysis, and by applying previously defined and tested signature profiles reflecting dysregulation of oncogenic signaling pathways and altered tumor environment. Results Elderly AML patients as expected had worse overall survival and event-free survival compared with younger patients. Analysis of oncogenic pathways revealed that older patients had higher probability of RAS, Src, and tumor necrosis factor (TNF) pathway activation (all P < .0001). Hierarchical clustering revealed that younger patients with AML in cluster 2 had clinically worse survival, with high RAS, Src, and TNF pathway activation compared with patients in cluster 1. However, among elderly patients with AML, those in cluster 1 also demonstrated high RAS, Src, and TNF pathway activation but this did not translate into differences in survival. Conclusion AML in the elderly represents a distinct biologic entity characterized by unique patterns of deregulated signaling pathway variations that contributes to poor survival. These insights should enable development and adjustments of clinically meaningful treatment strategies in the older patient population.

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