Tailoring Care: Advances in the Management of Acute Myeloid Leukemia

Acute myeloid leukemia (AML), a clonal hematopoietic stem cell cancer with diverse clinical presentation and progression, is characterized by overproduction of myeloblasts along with decreased production of red blood cells, platelets, granulocytes, and monocytes.¹ Patients with AML present with neutropenia, thrombocytopenia, and anemia. In 2020, the estimated number of new cases of AML was 19,940 (11,090 in men; 8850 in women).²

Counseling patients presenting with findings suggestive of AML poses a unique challenge for clinicians.¹ Although novel treatment strategies have improved patient outcomes over the past several decades, primary refractory rates remain around 20%, and up to 50% of patients will relapse after treatment.³ The pace of scientific discovery demands continuous education to understand current recommendations for a risk-adapted and tailored approach to AML treatment.

Assessment for Treatment

The diagnostic process for AML must be rapid. For patients, the diagnosis of AML can feel abrupt and life-changing. The complex journey from diagnosis, assessment, and management of adverse events while attempting to preserve some level of normalcy can be overwhelming to the patient and their caregivers.¹ 

Questions to discuss with the interdisciplinary care team include⁴:

1. Are there immediate life-threatening symptoms? 
   • If yes, what members of the interdisciplinary team are best suited to address these?
2. Is the patient’s primary language something other than English? 
   • If yes, are their immediate interpreter resources within the treatment center?
   • Are there other communication or health literacy barriers?
     • Visual impairment, hearing impairment
     • Cognitive deficits

3. Can the patient be treated locally?
   • If no, where is the closest treatment center?
4. What are the patient’s goals for care? 
   • Does the patient have advance directives?
   • Are the patient’s goals clinically realistic based on what is known about the disease at this time?
5. Does the patient have high-risk disease? 
   • If yes, will they need a transplant?
     • If yes, are they eligible for a transplant? 
     • Are there potential related donors?
6. Can the patient endure the induction therapy needed to rapidly suppress the malignant clone?
   • Does the patient have comorbidities? 
     • If yes, are they well controlled? 
   • What medication is the patient currently taking?
     • Will any of these medications need to be modified during leukemia treatment?
   • Which clinicians are responsible for managing each comorbidity/medication? 

For years, the predominant approach to treatment of AML was largely based on patient age and eligibility for aggressive treatment. Allogeneic hematopoietic stem cell transplant (allo-HCT) remains a standard of care for patients who meet eligibility criteria that include disease-related factors (remission status) and patient-related factors including physiologic, psychologic, social, and economic factors.^5,6 (A more comprehensive review of specific indications for allo-HCT are beyond the scope of this article.)

• AML with recurrent genetic abnormalities
• AML with myelodysplasia-related changes
• Therapy-related AML and myelodysplasia
• AML not otherwise specified
• Myeloid sarcoma
• Myeloid proliferations related to Down syndrome

In addition to eligibility and characteristics of the disease, the availability of a donor and a reliable caregiver are essential to allo-HCT treatment.⁶ Only those eligible for allo-HCT can expect longer survival; however, patients who undergo allo-HCT face numerous challenges including late effects of treatment, financial concerns, and psychosocial adjustment.¹ Those not eligible for allo-HCT are treated with low-intensity treatment indefinitely along with aggressive supportive care.¹

Clinicians should also consider clinical trials as most patients receiving currently available treatment will relapse without allo-HCT, and those undergoing allo-HCT may experience more severe and sometimes life-threatening adverse events.

Molecular Risk Stratification

Although eligibility for treatment remains an important consideration for allo-HCT, molecular risk stratification is now recommended in the initial evaluation of a patient suspected to have AML.⁵ Molecular and cytogenetic results are relevant for classification, prognosis, and increasingly, for therapy selection.⁹

Molecular analysis is necessary for the genomic classification of AML. Targeted agents are available for patients with several genetic mutations (FLT3, BCL2, IDH1, and IDH2) (Table).^1,9 Each of these targeted therapies requires specific monitoring and clinical management strategies. Some of these mutations are associated with resistance to standard chemotherapeutic agents. In addition, selected mutations are now thought to increase the risk for familial myeloid neoplasms, requiring a referral to a genetic counselor.^7-9 

Learning to interpret bone marrow biopsy and aspirate results including next-generation sequencing (NGS), metaphase cytogenetic, and general hematopathology results is an essential skill for clinicians working with these patients. Although complex, familiarity with the common molecular aberrations seen in patients with AML will facilitate treatment planning and discussions with patients and their caregivers about prognosis and treatment options. 

Comprehensive Assessment

A comprehensive assessment of the patient prior to initiation of therapy, including the presence of any other potential barriers to treatment is essential. Complete remission may be achieved initially with induction therapy, consisting of a blast of high-intensity conventional chemotherapy to wipe out as many of the leukemic cells as possible.^5,9

The physical impact of induction therapy, however, is difficult to describe to patients and their caregivers and requires detailed instructions to prepare them for the anticipated toxicities of treatment. Side effects may vary by patient and may occur within the first few days of treatment or in the days or weeks following treatment.⁴ Following induction therapy, healthy blood cells are transplanted to the patient (allo-HCT).

Involvement of clinicians from a variety of specialties and disciplines is required to optimize management of comorbidities and may ensure safe and effective treatment, mitigate adverse events, and maintain or improve quality of life.⁴

Clinicians working with these patients must be well versed in the complexity of the disease and the variability in treatment strategies. In addition, patients, their caregivers, and the health care team must work together to anticipate and mitigate adverse events.⁴ 

Laboratory Testing

Laboratory testing is obtained frequently during the induction phase of treatment to evaluate response and to identify any side effects that require treatment. Imaging studies may also be obtained based on individual signs and symptoms. Because pancytopenia is expected, these patients will inevitably develop 1 or more episodes of neutropenic fever requiring emergent management and hospitalization. Most patients will require transfusion support for red blood cells and platelets, intravenous fluids, and antibiotics during this time. Not all practices are equipped to provide this level of care in the outpatient setting and patients may either be hospitalized or referred to a tertiary center that specializes in cellular therapies. Successful management requires prompt interventions to avoid irreversible organ damage or death.^5,6

Role of the Caregiver

Although we focus largely on the patient with a diagnosis of AML, caregivers are essential in the process of diagnosis, treatment, and recovery. Caregiver expectations are outlined in several publications, but few discuss a detailed approach to caregiver training and support across the continuum.^6,10 Important questions to ask include⁴:

1. Does the patient have a primary caregiver, caregiver team, and/or support network?
   • If yes, who has medical power of attorney?
   • Does the person with medical power of attorney live locally?
     • If no, are they accessible for treatment decision-making currently?
   • If no, what other resources might the patient have
2. Does the patient/caregiver have to travel far to get to the treatment center?
   • If yes, does the patient have reliable transportation?
   • Is the patient homeless?
3. Is the patient working? 
   • If yes, how might treatment affect their ability to continue working? 
   • If they become unable to work, will they lose health insurance coverage?
4. Is the patient of childbearing age?
   • If yes, is fertility preservation possible?
   • Is the patient pregnant? If yes, how many weeks?

The continuing shift of care to the outpatient setting increases the urgency in developing strategies and programs for patient and caregiver support. Logistic necessities for outpatient treatment include reliable nonpublic transportation, a working cell phone, and housing arrangements within 30 to 60 minutes of the treatment center. Availability of a dedicated caregiver has been tied to a higher probability of surviving to 100 days after stem cell transplant (P =.42).¹¹

Caregivers are an extension of the professional clinical team and assume multiple roles for both inpatient and outpatient care and support of the patient. The multidimensional role of cancer caregivers includes direct care, indirect care, and emotional support. It is critical to have conversations and informational sessions with the patient and caregiver separately throughout the treatment and recovery process. Caregivers with higher preparedness before allo-HCT report significantly lower levels of depression (P =.02) and higher levels of caregiving competency (P <.001) and self-efficacy (P <.001) after transplantation.¹²

Building resiliency and reducing caregiver burden can reduce anxiety and depression and improve the overall health of the caregiver. Physical health problems, social problems, emotional problems, and financial problems should be evaluated at the time of diagnosis and reassessed throughout the continuum of care.¹² Building a caregiver team is recommended to allow the primary caregiver respite and to reduce the caregiver burden as well as reduce caregiver anxiety and depression, which have been associated with caregiver burnout.

Strategies for team communication across the continuum in particular points of transition are key as most patients will require 1 or more hospitalizations for treatment or acute events. Empowering the patient and their caregivers to be a partner in their care through patient-centered communication, shared decision-making, and a tailored approach to care will improve patient and caregiver engagement and patient outcomes.¹

Sandra Kurtin, PhD, ANP-BC, AOCN, FAPO is a hematology/oncology nurse practitioner at the University of Arizona Cancer Center, and assistant professor of Clinical Medicine and Adjunct Clinical Assistant Professor of Nursing at the University of Arizona.

References

1. Kurtin S, ed. Building Blocks of Hope: AML Edition. The MDS Foundation; 2021.

2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7-30. doi:10.3322/caac.21590

3. Goodman J. Adding idasanutlin to cytarabine does not improve os in the relapsed, refractory setting of acute myeloid leukemia. Oncology Nurse Advisor. Accessed September 13, 2022. https://www.oncologynurseadvisor.com/home/cancer-types/leukemia/acute-myeloid-leukemia-aml-cytarabine-idasanutlin-improve-survival/

4. Kurtin S. Interdisciplinary management of acute leukemia across the continuum of care. Semin Oncol Nurs. 2019;35(6):150953. doi.10.1016/j.soncn.2019.150953

5. Pollyea DA, Bixby D, Perl A, et al. NCCN Guidelines Insights: Acute Myeloid Leukemia, Version 2.2021. J Natl Compr Canc Netw. 2021;19(1):16-27. doi:10.6004/jnccn.2021.0002.

6. Kanate AS, Perales MA, Hamadani M. Eligibility criteria for patients undergoing allogeneic hematopoietic cell transplantation. J Natl Compr Canc Netw. 2020;18(5):635-643. doi.10.6004/jnccn.2020.7559

7. Döhner H, Weisdorf DJ, Bloomfield CED. Acute myeloid leukemia. N Engl J Med. 2015;373(12):1136-1152. doi:10.1056/NEJMra1406184

8. Hwang SM. Classification of acute myeloid leukemia. Blood Res. 2020;55(S1):S1-S4. doi:10.5045/br.2020.S001

9. Blum WG, Mims AS. Treating acute myeloid leukemia in the modern era: a primer. Cancer. 2020;126(21):4668-4677. doi:10.1002/cncr.32904

10. Yang MJ, Yepez VV, Brandon KO, et al. A mindfulness-based stress management program for caregivers of allogeneic hematopoietic stem cell transplant (HCT) patients: protocol for a randomized controlled trial. PLoS One.2022;17(4): e0266316. doi:10.1371/journal.pone.0266316

11. Song, Chen S, Roseman J, Scigliano, E, Redd WH, Stadler G. It takes a team to make it through: the role of social support for survival and self-care after allogeneic hematopoietic stem cell transplant. Front Psychol. 2021;12:624906. doi:10.3389/fpsyg.2021.624906

12. Winterling J, Kisch A, Alvariza A, Årestedt K, Bergkvist K. Preparedness for family caregiving prior to allogeneic hematopoietic stem cell transplantation. Palliat Support Care. 2022;20(4):519-526. doi:10.1017/S1478951521001346