AML

AML Pathophysiology

In AML, the expansion of undifferentiated myeloid precursors results in impaired hematopoiesis and bone marrow failure.1 According to the 2016 WHO classification, a diagnosis of AML is based on the presence of 20% or more blasts in the marrow or peripheral blood.2 Classification of AML requires a multidisciplinary approach using diagnostic testing including immunohistochemistry, cytochemistry, or both in addition to molecular genetics analysis.2 The importance of obtaining adequate samples of marrow or peripheral blood at diagnosis is emphasized throughout the current NCCN AML guideline. The WHO continues to classify AML entities by focusing on significant chromosomal and molecular subgroups.3

Cytogenetics-of-AML

For over 30 years, the molecular pathogenesis of AML has been studied.4 Molecular variations help determine the best course of treatment for each patient. Like cytogenetics, some of these molecular changes are linked to risks, stressing the importance of a person-centered approach in managing patients with AML.5 Some mutations are observed more frequently in certain age groups; For example, in patients < 60 years old mutations in DNMT3A and RUNX1 , while mutations in NPM1, FLT3, CEBPA and TP53 are the most important molecular risk factors in AML.6 Recurrent mutations in isocitrate dehydrogenase 1 and 2 genes (IDH1,IDH2) are found in myeloid malignancies and occur in about 12% of patients with AML.7

Molecular-Abnormalities

It is imperative to educate patients on prognostic factors when discussing treatment options such as the underlying factors that influence the choice of treatment (i.e. subtypes and response to therapy).5 Successful treatment depends on patient subtype of AML and age at diagnosis.8 As the front line of healthcare, oncology nurse professionals have a unique and vital role in educating patients of various health literacy levels on the expectations of current and emerging of AML.5 To accomplish this, they can explain the diversity of AML and what prognostic factors may indicate, monitor for adverse events and educate patients about potential therapeutic options post diagnosis.5  Additionally, oncology nurses can educate patients about the potential adverse events of treatment, monitor them, and assist in their mitigation.5  Potential eligibility for clinical trials should also be discussed with patients as applicable.

References:

  1. Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic Classification and Prognosis in Acute Myeloid Leukemia. N Engl J Med. 2016;374:2209-21.
  2. Acute Myeloid Leukemia (AML) NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Version I.2018 – February 7, 2018. Available: https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf Site Visited: May,2018
  3. Arber DA, Orazi A, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood2016 127:2391-2405; doi: https://doi.org/10.1182/blood-2016-03-643544
  4. Cancer Genome Atlas Research Network. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368:2059-74.
  5. Medical Learning Institute, Inc. and PeerView Institute for Medical Education. The Oncology Nurse Takes On AML: Insights on Recent Therapeutic Advances and Improving Patient Care. Available at: http://c.peerviewpress.com/onDemand/programs/150204261-2-2/downloads/PVI_monograph_QJG.pdf. Accessed May, 2018.
  6. Metzeler KH, Herold T, Rothenberg-Thurley M, et al. Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia. Blood. 2016;128:686-98
  7. Stein EM, et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood, 2017; Vol 130, Num 6
  8. A Study of Venetoclax in Combination With Low Dose Cytarabine Versus Low Dose Cytarabine Alone in Treatment Naive Patients With Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy. ClinicalTrials.gov Identifier: NCT03069352