Acute Myelogenous Leukemia: Genetics, Biology and Therapy


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Virtual Network's Login. Forgot your password? Register Here. ESH Video. Learning objectives 1. This meeting will be of interest to: Ph-students, post docs, junior and senior biologists and practicing clinicians MD, PhD, MD-PhD , hematologists and oncologists in training Residents and biologists still in-training. Accommodation Accommodation at special conference rates is available nearby the Estoril Congress Center, where the conference will take place.

Disclosure: Sekeres reports no relevant financial disclosures. Prolongation of OS has been the traditional goal of studies that involve patients with cancer because of the expected short survival of those with many types of cancer and the objective, unequivocal nature of the OS endpoint. However, other measures of benefit can be important for different types or stages of cancer.

Improvements in PFS and quality of life have been used as the basis for regulatory approval in solid tumors and lymphoproliferative diseases, with the understanding that there is less precision in the quantification of these and other surrogates.

Gemtuzumab ozogamicin Mylotarg, Pfizer is the only new drug approved for AML treatment in recent decades, based on a phase 2 trial of patients in relapse. Although the failure to identify newer, more potent cytotoxic agents is due to the recalcitrant nature of the disease rather than regulatory constipation, defining the burden of proof for approval remains a critical issue, particularly for new molecularly targeted and immunotherapeutic agents. In AML, considerations are potentially different for younger vs.


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In addition, AML is a biologically heterogeneous disease. Standard therapy is life threatening and cannot easily be administered to many older patients. The rate of complete remission CR with standard cytotoxic therapy is quite high in younger patients, a substantial fraction of whom can be cured. Because allogeneic transplantation is used in a nonsystematic fashion in many younger patients in CR, the evaluation of the effect of a new intervention on OS can be complex, even in randomized trials, and the use of EFS could be relevant.

Although there is some debate about the survival advantage of CR in older patients, there is a real clinical benefit to having normal blood counts and the quality-of-life improvement that accompanies this. In addition, benefit — as defined by any endpoint — must be balanced by the side-effect profile and the convenience of administration.

Thus, an oral therapy with few side effects might be approvable if the results were similar to those achieved with more intensive therapies that require hospitalization. This latter consideration is relevant for targeted therapies, the most recent examples of which are the IDH inhibitor AG Agios and the FLT3 inhibitor quizartinib Ambit Biosciences , which have produced CR as single agents in phase 2 trials in molecularly selected patients with relapsed AML.

Randomized trials are underway to compare these agents with chemotherapy regimens commonly used in such patients. One wonders whether the same requirement would have been applied to gemtuzumab ozogamicin if it were a new drug being developed in This raises the question of what response rate in phase 2 trials, taking into account the toxicity profile, would be sufficient for accelerated approval. For example, agents that target new resistance mutations in the epidermal growth factor receptor that produced at best partial responses recently were approved for patients with lung cancer.

The answer for patients with AML should depend on the clinical situation, the observed effect and side-effect profile of the new therapy in preliminary trials, and whether the target is known and inhibited. Regulatory agencies and clinical investigators utilize this thought process, and endpoints other than OS should be suitable in many circumstances. Charles A. He can be reached at schiffer karamanos. Disclosure: Schiffer reports no relevant financial disclosures.

Tell us what you think about Healio. Login Register My Saved. Cover Story. HemOnc Today, June 10, Please provide your email address to receive an email when new articles are posted on this topic. Receive an email when new articles are posted on this topic. You have already added this topic to your email alerts. Click here to manage your alerts. Acute myeloid leukemia, however, remains a notable exception. Advances in next-generation sequencing led to the identification of several potentially targetable driver mutations in AML.

A changing landscape Janet D. The extent of a mutation also is key.

How do novel molecular genetic markers influence treatment decisions in acute myeloid leukemia?

Tallman agreed, adding he expects midostaurin will be approved soon. Combinations and sequencing With so many therapies demonstrating single-agent activity, the next challenge for investigators will be to determine how best to sequence or combine them.


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For example, treatment-related adverse events are a key concern for older patients. Although time will tell, the findings from Ivey and colleagues could be pivotal, Burke wrote. Lancet agreed. J Clin Oncol. Burke MJ. N Engl J Med. Ivey A, et al. Lancet JE, et al. These are prevalent, and potentially clinically relevant because of the availability of tyrosine kinase inhibitors , such as imatinib and sunitinib that can block the activity of c-KIT pharmacologically.

The prognostic importance of other mutated genes e.

The overall cure rate for all people with AML including the elderly and those unable to tolerate aggressive therapy is likely lower. Relapse is common, and the prognosis is poor. AML is a relatively rare cancer. There are approximately 10, new cases each year in the United States, and the incidence rate has remained stable from through AML accounts for 1. The incidence of AML increases with age; the median age at diagnosis is 63 years.

There is some geographic variation in the incidence of AML. The first published description of a case of leukemia in medical literature dates to , when French physician Alfred-Armand-Louis-Marie Velpeau described a year-old florist who developed an illness characterized by fever, weakness, urinary stones , and substantial enlargement of the liver and spleen.

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Velpeau noted the blood of this person had a consistency "like gruel", and speculated the appearance of the blood was due to white corpuscles. Bennett; he used the term "leucocythemia" to describe this pathological condition. The term "leukemia" was coined by Rudolf Virchow , the renowned German pathologist , in As a pioneer in the use of the light microscope in pathology, Virchow was the first to describe the abnormal excess of white blood cells in people with the clinical syndrome described by Velpeau and Bennett. As Virchow was uncertain of the etiology of the white blood cell excess, he used the purely descriptive term "leukemia" Greek: "white blood" to refer to the condition.

Further advances in the understanding of acute myeloid leukemia occurred rapidly with the development of new technology. In , Paul Ehrlich developed a technique of staining blood films which allowed him to describe in detail normal and abnormal white blood cells.

Frontiers | Acute Myeloid Leukemia in Infants: Biology and Treatment | Pediatrics

Wilhelm Ebstein introduced the term "acute leukemia" in to differentiate rapidly progressive and fatal leukemias from the more indolent chronic leukemias. The technique of bone marrow examination to diagnose leukemia was first described in by Mosler. In , AML became the first cancer genome to be fully sequenced. DNA extracted from leukemic cells were compared to unaffected skin.

Leukemia is rarely associated with pregnancy, affecting only about 1 in 10, pregnant women. Acute leukemias normally require prompt, aggressive treatment, despite significant risks of pregnancy loss and birth defects , especially if chemotherapy is given during the developmentally sensitive first trimester. From Wikipedia, the free encyclopedia.

National Cancer Institute. Retrieved 19 December Retrieved 10 May The New England Journal of Medicine. Blueprints Pediatrics. Hematology: Basic Principles and Practice 4th ed. Louis, Mo. Clinical Oncology 3rd ed. Coleman; Mermel, Craig H. New England Journal of Medicine. J Clin Oncol. N Engl J Med. A review of the literature and a risk assessment".

Am J Epidemiol. The Leukemias: Epidemiologic Aspects. Oxford University Press , New York Distribution, incidence and appearance time". Leukemia 6th ed. Philadelphia: WB Saunders. International Journal of Hematology.

Acute Myelogenous Leukemia: Genetics, Biology and Therapy Acute Myelogenous Leukemia: Genetics, Biology and Therapy
Acute Myelogenous Leukemia: Genetics, Biology and Therapy Acute Myelogenous Leukemia: Genetics, Biology and Therapy
Acute Myelogenous Leukemia: Genetics, Biology and Therapy Acute Myelogenous Leukemia: Genetics, Biology and Therapy
Acute Myelogenous Leukemia: Genetics, Biology and Therapy Acute Myelogenous Leukemia: Genetics, Biology and Therapy
Acute Myelogenous Leukemia: Genetics, Biology and Therapy Acute Myelogenous Leukemia: Genetics, Biology and Therapy
Acute Myelogenous Leukemia: Genetics, Biology and Therapy Acute Myelogenous Leukemia: Genetics, Biology and Therapy
Acute Myelogenous Leukemia: Genetics, Biology and Therapy Acute Myelogenous Leukemia: Genetics, Biology and Therapy

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