- Recall the etiology and risk factors for AML
- Describe the presentation of AML
- Summarize the treatment of AML
- List the nursing diagnosis of AML
Acute myeloid leukemia (AML) is the most common leukemia among the adult population and accounts for about 80% of all cases. It is characterized by clonal expansion of immature “blast cells” in the peripheral blood and bone marrow resulting in ineffective erythropoiesis and bone marrow failure. With recent advancements in the management guidelines, the cure rates have increased up to 15% in patients older than 60 years and about 40% in patients below 60 years of age. Despite advancements in therapeutic regimens, the prognosis remains very poor in the elderly population.
In the past, French-American-British system classified AML into eight subtypes, FAB M0 to M7 which are as follows:
In 2016, World Health Organization (WHO) revised the classification and categorized it into AML with recurrent genetic abnormalities, AML with myelodysplasia-related changes, therapy-related myeloid neoplasms, NOS, myeloid sarcoma, myeloid proliferations related to Down syndrome.
AML with recurrent genetic abnormalities includes-
AML not otherwise specified (NOS) includes:
Based on the etiology of the AML, it can be categorized into de novo AML, Secondary AML (s-AML) which evolves from prior MPD or MDS and Therapy related AML (t-AML) following exposure to chemotherapeutic agents or radiation therapy or toxins.
The number of new cases among men and women per year is about 4.2 per 100,000 population. The incidence is over 20,000 cases per year in the United States. The average age at the time of diagnosis is about 65 years. It is more prevalent among non-Hispanic whites. Males have more predominance compared to females with a ratio of 5:3.
Due to ineffective erythropoiesis and bone marrow failure, patients experience a variety of symptoms including recurrent infections, anemia, easy bruising, excessive bleeding, headaches, and bone pains. Depending on the degree of anemia, they can experience generalized weakness, fatigue, shortness of breath and chest tightness. Physical examination can reveal bruises, pallor, hepatomegaly, and splenomegaly. Lymphadenopathy is rare. DIC is common in patients with APL.
AML should be suspected in anyone with unexplained cytopenias (decreased cell count of white blood cells, hemoglobin or platelets), the presence of circulating blast cells in the peripheral blood, easy bruising or bleeding or recurrent infections. In some cases, they can present with renal failure secondary to tumor lysis syndrome which is an oncologic emergency.
Presence of at least 20% blasts in the bone marrow or peripheral blood is diagnostic of AML. It can be diagnosed with bone marrow aspiration and biopsy. Additional diagnostics include flow cytometry, cytogenetics, and fluorescence in situ hybridization (FISH). Presence of Auer rods (clumps of azurophilic granules resembling elongated needles) is diagnostic of AML. Auer rods can be seen in many subtypes of AML, but abundantly seen in APL.
Oncologic emergencies associated with AML include neurologic or respiratory distress due to leukostasis, APL-induced DIC, tumor lysis syndrome, and central nervous system (CNS) involvement.
Individuals who achieve complete remission (CR) with a blast count of less than 5% in the bone marrow after induction therapy tend to have increased survival. Despite induction therapy, there is still minimal residual disease for which consolidation therapy is initiated to prevent any risk of relapse by eliminating the residual disease. Despite many advances, the mainstay of therapy remains a combination of cytarabine-based and anthracycline-based regimens. For eligible candidates, allogeneic stem cell transplantation should be considered.
This is a standard of care for younger patients, elderly with low risk of treatment-related mortality (TRM), and ones with favorable and intermediate-risk factors. The induction therapy is highly toxic to bone marrow causing pancytopenias and bleeding complications, gastrointestinal system issues, kidney failure due to tumor lysis syndrome, and electrolyte disturbances. It may take up to 1 month for the cell counts to recover, and these patients need aggressive monitoring to manage any complications. Baseline cardiac function should be estimated before initiating the treatment, and the ejection fraction (EF) needs to be monitored carefully, as anthracyclines can cause significant cardiotoxicity. Studies have shown greater benefit with higher doses, but toxicities may limit its use. It consists of "7+3" regimen that includes continuous infusion of cytarabine for seven days along with anthracycline on days 1 to 3. Patients with the refractory disease have shown higher CR and similar overall survival (OS) by using higher doses of cytarabine or by using a combination of fludarabine, cytarabine, and idarubicin. Despite TRM in elderly, chemotherapy has shown to improve the survival rate among elderly (older than 65 years). Decitabine, a methylating agent, used in the treatment of MDS, has shown improvement in OS in the elderly population. The response should be evaluated by repeating the bone marrow aspirate and biopsy after 2 weeks of initiating the induction therapy. Reinduction can be done with high dose cytarabine or by combining with etoposide if there is persistent evidence of disease. About 60% to 80% de novo AML will achieve CR with induction therapy.
Even before the diagnosis, if APL is suspected, then the treatment should be initiated with all-trans retinoic acid (ATRA), as early use of ATRA decreases the risk of disseminated intravascular coagulation (DIC) and mortality associated with it.
After achieving CR with induction therapy, consolidation therapy is initiated with high dose cytarabine, called HiDAC and hematopoietic cell transplantation (HCT). HCT is preferred in individuals with less than 60 years of age with intermediate or unfavorable prognosis. If a donor is available, then allogenic HCT is preferred over autologous HCT. They should be Monitored for signs or symptoms of acute or chronic graft versus host disease (GVHD).
Ongoing studies with Fms-like tyrosine kinase 3 (FLT3) inhibitors, IDH inhibitors, and immune therapies.
AML is a common hematological malignancy in adults. Despite many advances, the malignancy still carries a poor prognosis. Hence, it is best managed by a multidisciplinary team that includes a hematologist, oncologist. internist, pathologist, and an intensivist. The oncology nurse is vital for treatment administration and monitoring for potential complications. The pharmacist should educate the patient on potential adverse effects of the potent drugs used to treat this malignancy. The primary care physician should educate the patient on personal hygiene, hand washing, and immunization. Overall, the life expectancy has increased slightly but most patients have a markedly shortened lifespan.
AML is a common hematological malignancy in adults. Despite many advances, the malignancy still carries a poor prognosis. Hence, it is best managed by an interprofessional team that includes a hematologist, oncologist. internist, pathologist, and an intensivist. The key is to prevent more harm to the patient and hence a universal treatment plan must be developed and carried out.
The pharmacist should educate the patient on the chemotherapeutic drugs, their benefits, and adverse effects. The oncology nurse is vital for treatment administration and monitoring for potential complications.
The nurse should educate the patient on infection prevention by washing hands, rinsing all fruits and vegetables, avoiding crowds and seeking help at the first sign of fever.
The radiologist is essential for placement of long term venous catheters and other imaging studies. The primary care physician should educate the patient on personal hygiene, hand washing, and immunization. The dietitian should help manage nutrition and the social work should ensure that the patient has all the support to complete the treatment.
Bain BJ,Béné MC, Morphological and Immunophenotypic Clues to the WHO Categories of Acute Myeloid Leukaemia. Acta haematologica. 2019 [PubMed PMID: 30965338]
Naymagon L,Marcellino B,Mascarenhas J, Eosinophilia in acute myeloid leukemia: Overlooked and underexamined. Blood reviews. 2019 Jul [PubMed PMID: 30948162]
Medeiros BC,Chan SM,Daver NG,Jonas BA,Pollyea DA, Optimizing survival outcomes with post-remission therapy in acute myeloid leukemia. American journal of hematology. 2019 Jul [PubMed PMID: 30945331]
Hartmann L,Metzeler KH, Clonal hematopoiesis and pre-leukemia -genetics, biology and clinical implications. Genes, chromosomes [PubMed PMID: 30939217]
Boddu PC,Zeidan AM, Myeloid disorders after autoimmune disease. Best practice & research. Clinical haematology. 2019 Mar [PubMed PMID: 30927978]
Liu XJ,Huang XJ,Xu LP,Liu KY,Zhang XH,Yan CH,Wang Y, [Effects of pre-transplant course on prognosis of allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia]. Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi. 2019 Mar 14 [PubMed PMID: 30929382]
Leisch M,Jansko B,Zaborsky N,Greil R,Pleyer L, Next Generation Sequencing in AML-On the Way to Becoming a New Standard for Treatment Initiation and/or Modulation? Cancers. 2019 Feb 21 [PubMed PMID: 30795628]
Dong XY,Li YL,Jiang L,Wu CY,Shang BJ,Zhang L,Cheng W,Zhu ZM, [Correlation between myeloperoxidase expression and gene alterations and prognosis in acute myeloid leukemia]. Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi. 2019 Jan 14; [PubMed PMID: 30704227]
Schmid C,Labopin M,Schaap N,Veelken H,Schleuning M,Stadler M,Finke J,Hurst E,Baron F,Ringden O,Bug G,Blaise D,Tischer J,Bloor A,Esteve J,Giebel S,Savani B,Gorin NC,Ciceri F,Mohty M,Nagler A, Prophylactic donor lymphocyte infusion after allogeneic stem cell transplantation in acute leukaemia - a matched pair analysis by the Acute Leukaemia Working Party of EBMT. British journal of haematology. 2019 Mar; [PubMed PMID: 30467839]
Nabhan C,Kamat S,Karl Kish J, Acute myeloid leukemia in the elderly: what constitutes treatment value? Leukemia & lymphoma. 2019 May [PubMed PMID: 30407103]
Duan WB,Gong LZ,Jia JS,Zhu HH,Zhao XS,Jiang Q,Zhao T,Wang J,Qin YZ,Huang XJ,Jiang H, [Clinical features and early treatment effects in intermediate risk and poor risk acute myeloid leukemia with EVI1 positive]. Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences. 2017 Dec 18; [PubMed PMID: 29263470]
Lin M,Chen B, Advances in the drug therapies of acute myeloid leukemia (except acute wpromyelocytic leukemia). Drug design, development and therapy. 2018 [PubMed PMID: 29750014]
Schoen MW,Woelich SK,Braun JT,Reddy DV,Fesler MJ,Petruska PJ,Freter CE,Lionberger JM, Acute myeloid leukemia induction with cladribine: Outcomes by age and leukemia risk. Leukemia research. 2018 May [PubMed PMID: 29574395]
Strickland SA,Shaver AC,Byrne M,Daber RD,Ferrell PB,Head DR,Mohan SR,Mosse CA,Moyo TK,Stricker TP,Vnencak-Jones C,Savona MR,Seegmiller AC, Genotypic and clinical heterogeneity within NCCN favorable-risk acute myeloid leukemia. Leukemia research. 2018 Feb; [PubMed PMID: 29310020]
Fujiwara Y,Yamaguchi H,Yui S,Tokura T,Inai K,Onai D,Omori I,Marumo A,Yamanaka S,Sakaguchi M,Terada K,Nakagome S,Arai K,Kitano T,Okabe M,Okamoto M,Tamai H,Nakayama K,Tajika K,Wakita S,Inokuchi K, Importance of prognostic stratification via gene mutation analysis in elderly patients with acute myelogenous leukemia. International journal of laboratory hematology. 2019 Aug [PubMed PMID: 30970181]