Another factor to consider is the age of onset of AML, as older adults typically have less optimal response and poorer ability to tolerate chemotherapy and transplant compared with children and young adults. If an older adult is at risk for AML, the question then is not only if pHSCT should be performed but also what would be the optimal age for pHSCT. Another consideration is that some patients are at heightened risk for serious adverse events following standard AML treatment, which can preclude transplantation or even negatively affect its outcome. In these cases, early intervention may be necessary, but the dilemma is selecting the optimal time.
The fourth factor is to consider outcomes without pHSCT. That can be problematic because many of these syndromes are quite rare or have only recently been identified, and information is limited regarding disease penetrance, clinical features, and longer-term outcomes with or without transplant.
Of note, clinicians must consider whether performing pHSCT is really in the best interest of the patient, despite its potential for preventing the onset of leukemia. Having an underlying predisposition, for example, does not mean that leukemia will subsequently develop. For example, in a hypothetical scenario with 50% penetrance offered by the authors, half of pHSCT recipients would never have developed leukemia, and thus pHSCT would subject these patients to a signiﬁcant and arguably unnecessary risk. However, in a different hypothetical scenario with 90% penetrance where 90% of patients would develop leukemia, pHSCT would prevent the need for chemotherapy and eliminate the risk for second primary AML in most of the cohort.
“Thus, the scales between beneﬁcence and nonmaleﬁcence (“do no harm”) tip based on complex probabilities and many uncertainties,” the authors wrote.
Another ethical consideration is that of treating all patients alike, or a “one size fits all” approach. Clinicians need to consider whether the available evidence supports offering or even encouraging pHSCT for all patients with a syndrome that puts them at risk of subsequently developing AML. More emphasis is being placed on value-based cancer care, and thought must be given as to whether pHSCT provides value for these patients and whether it conflicts with a patient’s personal values.
“One key point here is that physicians should not be weighing the risks and benefits independently; they should be involving their patients in these conversations,” explained Hamilton. “Each individual patient will likely perceive the risks and benefits differently based on their personal experiences, and it is important to consider not just the potential medical implications but also the psychosocial implications.”
She added that a “multidisciplinary approach should be used involving oncologists, transplant doctors, genetics, social work, and psychology.”
1. Hamilton KV, Maese L, Marron JM, Pulsipher MA, Porter CC, Nichols KE. Stopping leukemia in its tracks: Should preemptive hematopoietic stem-cell transplantation be offered to patients at increased genetic risk for acute myeloid leukemia? [published online June 6, 2019]. J Clin Oncol. doi:10.1200/JCO.19.00181