Learning Outcome

1. Recall the etiology and risk factors for AML
2. Describe the presentation of AML
3. Summarize the treatment of AML
4. List the nursing diagnosis of AML

Introduction

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.[1][2][3]

Nursing Diagnosis

• Anorexia
• Fatigue, malaise
• Weakness
• Bruising
• Bone pain
• Fever
• Frequent infections
• Nose bleeds

Causes

Depending upon the etiology, genetics, immune-phenotype, and morphology, there are different classification systems for AML.[4][5]

In the past, French-American-British system classified AML into eight subtypes, FAB M0 to M7 which are as follows:

• M0: Undifferentiated AML
• M1: AML with minimal maturation
• M2: AML with maturation
• M3: Acute promyelocytic leukemia (APL)
• M4: Acute myelomonocytic leukemia
• M5: Acute monocytic leukemia
• M6: Acute erythroid leukemia
• M7: Acute megakaryocytic leukemia

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 with t(8;21)(q22;q22.1); RUNX1-RUNX1T1
• AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11
• APL with t(15;17)(q22;q12); PML-RARA
• AML with t(9;11)(p21.3;q23.3); MLLT3-KMT2A
• AML with t(6;9)(p23;q24); DEK-NUP214
• AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM
• AML (megakaryoblastic) with t(1;22)(p13.3;q13.3); RBM15-MKL1
• AML with mutated NPM1
• AML with biallelic mutations CEBPA

 AML not otherwise specified (NOS) includes:

• AML with minimal differentiation
• AML without maturation
• AML with maturation
• Acute myelomonocytic leukemia
• Acute monoblastic/monocytic leukemia
• Pure erythroid leukemia
• Acute megakaryoblastic leukemia
• Acute basophilic leukemia
• Acute panmyelosis with myelofibrosis

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.

Risk Factors

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.

Assessment

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.

Evaluation

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.[6][7][8][9]

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.[10]

Medical Management

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.[11][12][13][14]

Induction Therapy

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.

Consolidation Therapy

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).

Novel Targets

Ongoing studies with Fms-like tyrosine kinase 3 (FLT3) inhibitors, IDH inhibitors, and immune therapies.

Nursing Management

• Check labs for coagulation parameters
• Check vitals
• Provide skin protection
• Monitor for infection and sepsis
• Promote normothermia
• Educate the patient and family
• Monitor ins and outs
• Check if nutrition is sufficient
• Promote hand washing
• Encourage self care

When To Seek Help

• Fever
• Hypotension
• Bleeding
• LOC
• Altered mental status
• Severe bruising
• Pain

Outcome Identification

• Normal appetite
• Vitals stable
• No signs of infection
• Afebrile
• No pain

Monitoring

• Vitals
• Ins and outs
• Body weight
• Neurovitals
• Dehydration
• Nutrition
• Signs of infection

Coordination of Care

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.[15][16]

Health Teaching and Health Promotion

• Wash hands
• Rinse all fruits and vegetables
• Avoid crowds
• Maintain good personal hygiene
• Follow up with a clinician
• Take medications as prescribed

Discharge Planning

• Wash hands
• Rinse all fruits and vegetables
• Avoid crowds
• Maintain good personal hygiene
• Follow up with clinician
• Take medications as prescribed

Pearls and Other issues

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.