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ASH clinical practice guidelines for treating AML in older adults

The American Society of Hematology (ASH) has worked in partnership with the McMaster GRADE Center to release new guidelines for the treatment of newly diagnosed acute myeloid leukemia (AML) in older adults.1 These recommendations were established through a systematic review of all available evidence, with the aim that these guidelines would help improve critical care decisions made by healthcare professionals for this vulnerable population.

With a median diagnosis age of 68 years in the U.S, AML is far more common in the elderly.2 Within this particular age group, AML has an especially bleak outcome with <5% of patients being alive within five years post-diagnosis, compared to 40% in the young.3,4

A patient between 65–74 years can expect to live for a year or two following diagnosis, and the three-year survival rate is only 1 in 5. Even comparing a patient 75-years old and over, there are apparent disparities with the disease prognosis becoming increasingly poor. Life expectancy is measured in months, with the three-year survival rate decreasing to < 4% and only 1 in 5 surviving one year after diagnosis.2

The dramatic age-related outcome disparities associated with AML in the elderly is multifactorial, focusing on three different influences: patient, disease biology, and the available healthcare system.2

Patient status plays a huge role in prognosis, as older adults often have a reduced tolerance to intensive therapy due to functional status, such as frailty and fitness, and frequent comorbidities. AML disease biology differs in older adults compared with younger adults, and the elderly hold unfavorable genetic factors such as an increased incidence of multiple chromosomal abnormalities. Finally, the available healthcare system influences prognosis due to potential physician and patient reluctance to initiate therapy.2 All of these lead to poor outcomes in older adults diagnosed with AML.

All of this considered, the ASH and McMaster GRADE Centre have made a concerted effort to develop new guidelines to address this age-related outcome disparity. The guidelines were formed of panels composed of international experts, in areas including hematology, geriatric oncology, epidemiology and palliative care. Further to this, each panel included experts in methodology, evidence synthesis and guideline development. One patient representative was present on each panel, working collaboratively with the medical experts throughout the process.5

The panels began by constructing a list of clinical questions and outcomes of interest that were generated from a brainstorming exercise. Each panel rated the listed outcomes of interest on importance, based on literature reviews, and those identified as highest were further refined.5

Thorough systematic reviews were conducted based on intervention effects, and evidence gathered with relation to:

  • Baseline risks
  • Values
  • Preferences and
  • Costs

Once the findings were summarized within the GRADE Evidence-to-Decision (EtD) framework, recommendations were developed and after review, the guidelines were complete.5

The new guidelines included six recommendations, of which they were labelled as either ‘strong’, followed by the panel using the word “recommends”, or ‘conditional’, followed by the panel using the word “suggests”. All are in the context of older adults with AML.2

Recommendation 1.
For patients who are candidates for such therapy, the ASH guideline panel recommends offering antileukemic therapy over best supportive care.
Recommendation 2.
For patients considered candidates for intensive antileukemic therapy (see rec. 1), the ASH guideline panel suggests intensive antileukemic therapy over less-intensive antileukemic therapy.
Recommendation 3.
For patients who achieve remission after at least a single cycle of intensive antileukemic therapy and who are not candidates for allogeneic hematopoietic stem cell transplantation (HSCT), the ASH guideline panel suggests post-remission therapy over no additional therapy.
Recommendation 4a.
For patients considered appropriate for antileukemic therapy but not for intensive antileukemic therapy, the ASH guideline panel suggests using either of the options when choosing between hypomethylating-agent monotherapy and low-dose-cytarabine monotherapy.
Recommendation 4b.
For patients considered appropriate for antileukemic therapy, such as hypomethylating agents (azacytidine and decitabine), but not for intensive antileukemic therapy, the ASH guideline panel suggests using monotherapy with 1 of these drugs over a combination of 1 of these drugs with other agents.
Recommendation 5.
For patients who achieve a response after receiving less-intensive therapy, the ASH guideline panel suggests continuing therapy indefinitely until progression or unacceptable toxicity over stopping therapy.
Recommendation 6.
For patients who are no longer receiving antileukemic therapy (inc. those receiving end-of-life care), the ASH guideline panel suggests having red blood cell transfusions available over not having transfusions available.

The ASH emphasize that the guidelines are focused on patient decision making and patient goals. They state that their guidelines are sensitive to that thought process and in identifying what a patient’s goals are prior to proceeding to the step of determining what treatment to give.1

These guidelines are important on a clinical level due to the world’s older population growing dramatically. The ‘baby boomer’ generation born between 1946 and 1965 are now aged 55 to 74 and considering the statistics presented earlier, the aging population will lead to an increase in prevalence of AML.2

These guidelines will help to standardize the care that older patients receive for AML. The framework will guide clinicians with the critical care decisions they make, from the time of the patients’ diagnosis, through post-remission therapy, to considerations for end-of-life/hospice care.

Written by Frankie Lewns

Edited by Tom Southgate

  1. Hematology. ASH Clinical Practice Guidelines on Acute Myeloid Leukemia in Older Adults. Available from: https://www.hematology.org/education/clinicians/guidelines-and-quality-care/clinical-practice-guidelines/acute-myeloid-leukemia-guidelines (Last accessed 26/08/20).
  2. Sekeres M, Guyatt G, Abel G, et al. American Society of Hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults. Blood Advances. 2020;4(suppl 15):3528-3549.
  3. Alibhai S, Leach M, Minden M, et al. Outcomes and quality of care in acute myeloid leukemia over 40 years. Cancer. 2009;115(suppl 13):2903-2911.
  4. Menzin J, Lang K, Earle C, et al. The outcomes and costs of acute myeloid leukemia among the elderly. Arch Intern Med. 2002;162(suppl 14):1597-1603.
  5. Hematology. AML Guideline Development Process. Available from: https://www.hematology.org/education/clinicians/guidelines-and-quality-care/clinical-practice-guidelines/acute-myeloid-leukemia-guidelines/aml-guideline-development-process (Last accessed 26/08/20).