Code Status Transitions in Patients with High-Risk Acute Myeloid Leukemia (AML)
Authors: Abrams Hannah R. , Nipp Ryan D. , Traeger Lara , Lavoie Mitchell W. , Reynolds Matthew J. , LeBlanc Thomas W. , El-Jawahri Areej 
Published: November 2021

Abstract
Background:
Patients with high-risk AML often experience intensive medical care at the end of life (EOL) such as hospitalization and intensive care unit (ICU) admission. Despite their poor prognosis, patients with AML and their caregivers often have substantial misperceptions of their prognosis, which may lead to difficult code status transitions near the end of life. However, studies examining code status transitions in patients with AML are lacking.
Methods:
We conducted a mixed-methods study of 200 patients with high-risk AML enrolled in supportive care studies at Massachusetts General Hospital between 2014-2021. High-risk AML was defined as: 1) new diagnosis ≥ 60 years, or 2) relapsed/refractory AML. Two physicians used consensus-driven medical record review to characterize code status transitions from time of diagnosis to death and identify patient, family, and palliative care involvement. Code status was coded as 'full' (confirmed or presumed), 'restricted' (i.e., do not resuscitate), or 'comfort measures only' (CMO). We used logistic regression to explore whether patient factors or features of the code status discussion were associated with the time between the last code status transition and death.
Results:
At diagnosis of high-risk AML, 86.0% of patients were 'full code' (38.5% presumed, 47.5% confirmed) and 8.5% had restrictions on life-sustaining therapies. Overall, 57% (114/200) of patients experienced a code status transition, with a median of two transitions (range 1-8) during their illness course. Overall, a total of 206 code status transitions were described across the cohort. Median time from diagnosis to first code status transition was 212 days (range 7-4507), and from last transition to death was 2 days (range 0-350). Most of these final code status transitions (71.1%, 81/114) were transitions to CMO near the end of life. Only 60.5% of patients (69/114) who underwent a code status transition participated in their last code status change. In contrast, patients and families participated in 87.7% (100/114) of the last code status transitions and palliative care was involved in 42.1% (48/114). A substantial minority of last code status transitions occurred in the ICU or emergency department (26.3%, 30/114). We identified three processes leading to code status transitions (Table 1): 1) pre-emptive conversations prior to any clinical change (15.6%, 32/206); 2) anticipatory conversations at the time of acute clinical deterioration (32.2%, 66/206); and 3) futility conversations after acute clinical deterioration, focused on withdrawing life-sustaining therapies (51.0%, 105/206). Older age (B = 0.07, P &lt; 0.001), and receipt of non-intensive chemotherapy (B = 1.42, P = 0.003) were associated with a longer time from the last code status transition to death (Table 2). In contrast, futility conversations were associated with shorter time from last code status transition to death (B = -2.84, P &lt; 0.001) compared to pre-emptive or anticipatory conversations.
Conclusions:
Almost half of patients were "presumed full code" at the time of diagnosis of high-risk AML and most experienced code status transitions at the end of life focused on futility of life-sustaining therapies after acute clinical deterioration. These results suggest that goals of care discussions occur too late in the typical illness course of patients with poor prognosis, high-risk AML. Interventions focused on enhancing patient engagement in timely discussions regarding their end of life care preferences are warranted.
Figure 1 Figure 1.

Disclosures
LeBlanc: AbbVie: Consultancy, Honoraria, Other: Advisory board; Travel fees, Speakers Bureau; BMS/Celgene: Consultancy, Honoraria, Other: Travel fees, Research Funding, Speakers Bureau; Pfizer: Consultancy, Other: Advisory Board; Daiichi-Sankyo: Consultancy, Honoraria, Other: Advisory board; Flatiron: Consultancy, Other: Advisory board; Astellas: Consultancy, Honoraria, Other: Advisory board; American Cancer Society: Research Funding; Jazz Pharmaceuticals: Research Funding; AstraZeneca: Consultancy, Honoraria, Other: Advisory board, Research Funding; Agios: Consultancy, Honoraria, Other: Advisory board; Travel fees, Speakers Bureau; Duke University: Research Funding; Otsuka: Consultancy, Honoraria, Other; NINR/NIH: Research Funding; CareVive: Consultancy, Other, Research Funding; Helsinn: Consultancy, Research Funding; Heron: Consultancy, Honoraria, Other: advisory board; Amgen: Consultancy, Other: travel; UpToDate: Patents & Royalties; Seattle Genetics: Consultancy, Other: Advisory board, Research Funding.