Overcoming the challenges of treating the older patient with AML

Treatment outcomes in patients with Acute Myeloid Leukemia (AML) continuously decline with progressively increasing age and this presents many challenges to clinical hematologists. G. Ossenkoppele and B. Löwenberg examined the available treatment options to improve clinical outcomes in older patients and made the following recommendations in Blood in January 2015:

In older patients, there should be a deliberate therapeutic plan that relates to the individual circumstances and this plan should be adhered to as much as possible. This plan should be followed even though concomitant problems may urge the modification and temporary deviation from the original objectives.

As an initial priority, follow the same therapeutic principles that are applied in younger adults provided the medical situation of the patient allows for intensive induction chemotherapy. This implies that intensive remission induction chemotherapy is the first choice whenever this is considered realistic and feasible on clinical grounds.

Non-myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) being reasonably well tolerated in terms of early toxicity has shifted the age limit of the applicability of allogeneic HSCT upward. Allogeneic HSCT after reduced-intensity conditioning currently provides anti-leukemic effectiveness that is not much different from ablative allogeneic HSCT.

In a general sense, the molecular features that characterize the risk of AML in middle-aged adults also apply to older adults with AML, although the incidence of unfavorable genotypes is significantly more frequent among older adults. These genetic disease-related features of the leukemia furnish clinically informative prognostic insights and thus may offer useful guidance during the therapeutic treatment of an individual patient.

It is recommend whenever possible to include older AML patients in well-designed clinical trials. This provides some guarantee for quality of treatment (e.g., protocolized treatment according to state-of-the-art standards), but it also offers the opportunity to contribute to progress in this still devastating disease.

Today, older patients with AML can be offered one of the following treatment options:

• Standard induction treatment consisting mostly of a 3+7 regimen of an anthracycline and Ara-C
• Hypomethylating agents
• Investigational drugs within a clinical trial
• Low-dose Ara-C
• Best supportive care with oral cytostatic drugs such as hydroxyurea and/or transfusions
   

Abstract

Acute myeloid leukemia (AML) in older patients presents a notable therapeutic challenge to the clinical hematologist. The clinical biology of AML among patients is highly heterogeneous. Interpatient variations are relevant for prognosis and treatment choice. Outcome of treatment for patients of advanced age is often compromised by comorbid conditions and an enhanced susceptibility to toxicities from therapy. Here we present selected clinical vignettes that highlight distinct representative situations derived from clinical practice. The vignettes are specifically discussed in light of the perspective of treating older patients with leukemia. We review the clinical significance of various cytogenetic and molecular features of the disease, and we examine the various currently available treatment options as well as the emerging prognostic algorithms that may offer guidance in regard to personalized therapy recommendations. The dilemmas in tailoring treatment selection in this category of patients with AML are the central theme in this discussion.