General AML

How I treat Acute Myeloid Leukemia patients presenting with pre-existing comorbidities

Numerous patients with Acute Myeloid Leukemia (AML), especially older patients, present with pre-existing comorbidities at diagnosis. These concomitant conditions cause additional challenges for treating physicians in terms of polypharmacy interactions, how to confidently asses the risk benefit ratios of managing each condition, as well as the patient’s AML, and the fact that there is a paucity of treatment guidelines.

Y.Ofran., et al., have provided case studies on common clinical scenarios relating to organ dysfunction. The authors focused on induction and consolidation with some reference to allogeneic transplantation. This practical guide was published in Blood in 2016.

The key guidance for the clinical scenarios was as follows:
Patient with cardiomyopathy

It may be entirely reasonable to offer standard induction therapy with very close cardiac monitoring.

The choice is very individualized and will take into account the patient’s age, performance status and any comorbidities.

In general, patients with cardiomyopathy, if clinically stable, need not preclude therapy for AML.

Patient with Acute Coronary Syndrome (ACS)

For this patient, immediate medical therapy should include the combination of aspirin, beta-blockers, allopurinol, hydration, correction of electrolyte imbalances, and maintenance of hemoglobin level of 8 g/dL.

If signs or symptoms of ischemia persist, percutaneous coronary intervention (PCI) should be discussed. Intractable ischemia must be resolved prior to initiating induction therapy.

In conclusion, the presence of ACS should not discourage aggressive therapy for AML.

Patient with newly diagnosed AML, diabetes and renal failure

Effective collaboration between the hematologist and nephrologist is required. The most pertinent clinical concern to first resolve is the potential for tumor lysis syndrome (TLS). 

The best approach to induction and post-remission therapy in a patient with chronic renal failure is unknown.

Cytarabine can still be used with dose adjustments according to the patient’s creatinine clearance.

Overall, renal dysfunction presents a significant barrier to treatment of AML. Scrupulous attention to metabolic abnormalities and chemotherapy dose adjustment are crucial.

Patient with Hepatitis B

Prophylaxis is essential for patients receiving severe immunosuppressive therapy. AML induction and consolidation therapy falls into this category. 

The efficacy of such prophylaxis has been demonstrated in several controlled trials. Prophylaxis, induction and consolidation therapy can be given at standard doses and if indicated, allogeneic transplantation can be undertaken.

The presence of antibody to HBsAg may offer some protection, but this is probably insufficient to discard prophylaxis.

Patient with cirrhosis of the liver

Allogeneic transplantation is obviously hazardous and would not be carried out for a patient with uncompensated cirrhosis.

In contrast, for a patient with Child I cirrhosis who is in CR, RIC transplantation could be considered.

Cirrhosis of the liver presents a serious dilemma; dose reduction is often required and curative options are usually precluded if associated with severe hyperbilirubinemia.

Patient with Chronic Obstructive Pulmonary Disease (COPD)

AML patients with COPD are usually excluded from clinical trials and presents many complications.

In addition, pulmonary hypertension raises the mortality from sepsis.

Patient treatment should be evaluated in relation to the Sorror comorbidity indices.

Hypomethylating therapy may be an alternative to intensive induction as it may be efficacious for “low proliferative” leukemia as well as in frail patients.

Overall, the absence of unequivocal guidelines means that the approach to therapy requires experience, careful judgment and subspecialty support.

Patient with Intracranial Hemorrhage (ICH)

In a patient with a prior ICH, blood pressure control reduces recurrent central nervous system (CNS) bleeding risk by 50%.

Urgent anti-leukemic therapy with the aim to control the blast count is indicated because hyperleukocytosis is associated with increasing bleeding risk.

Patients with ICH can receive optimal induction therapy, provided the platelets are kept at relatively safe levels.

In older patients, in whom the risk of re-bleeding is significantly high and allogeneic transplantation is not a practical option, less myeloablative therapy should be considered.

But how can a treating physician gain the expertise and confidence? Dr Rowe one of the authors made the following statement when this question was posed to him:

AGP hub: How did you gain the expertise in order to confidently manage AML patients with pre-existing co-morbidities?
 

Dr Rowe:  Through 38 years of hands-on experience, seeing patients year round, working with outstanding colleagues and being inspired by patients who gave us strength where none seemed possible.

In conclusion, the management of these pre-existing comorbidities in AML requires careful consideration and effective collaboration with other specialities in order to facilitate the most appropriate treatment plan for patient’s individual circumstances.

Abstract

Acute myeloid leukemia (AML) is a devastating disease with an incidence that progressively increases with advancing age. Currently, only ∼40% of younger and 10% of older adults are long-term survivors. If untreated, the overall prognosis of AML remains dismal. Initiation of therapy at diagnosis is usually urgent. Barriers to successful therapy for AML are the attendant toxicities directly related to chemotherapy or those associated with inevitable aplasia. Organ dysfunction often further complicates such toxicities and may even be prohibitive. There are few guidelines to manage such patients and the fear of crossing the medico-legal abyss may dominate. Such clinical scenarios provide particular challenges and require experience for optimal management. Herein, we discuss select examples of common pre-treatment comorbidities, including cardiomyopathy, ischemic heart disease; chronic renal failure, with and without dialysis; hepatitis and cirrhosis; chronic pulmonary insufficiency; and cerebral vascular disease. These comorbidities usually render patients ineligible for clinical trials and enormous uncertainty regarding management reigns, often to the point of withholding definitive therapy. The scenarios described herein emphasize that with appropriate subspecialty support, many AML patients with comorbidities can undergo therapy with curative intent and achieve successful long-term outcome.

References
  1. Ofran Y. et al. How I treat acute myeloid leukemia presenting with pre-existing comorbidities. Blood. 2016. 128:488-496; DOI:10.1182/blood-2016-01-635060.