Symptom Burden, Quality of Life, and Distress in Acute Myeloid Leukemia Patients Receiving Induction Chemotherapy: Results of a Prospective Electronic Patient-Reported Outcomes Study

Background: Induction chemotherapy for acute myeloid leukemia (AML) is more intensive than many other cancer treatments, and may be associated with a different symptom burden. Little is known about the most prevalent symptoms during AML induction, nor how they change over time, and with remission status. Similarly, little is known about the trajectory of quality of life (QoL) and distress scores in this population. We aimed to learn more about the natural history of these issues via a prospective, longitudinal, observational patient-reported outcomes study.

Methods: We enrolled 43 inpatients with AML at initiation of induction chemotherapy, and assessed their symptoms, quality of life (QoL), and distress weekly during their month-long hospitalization for induction, and monthly thereafter, using 3 validated instruments: Patient Care Monitor v2.0 (PCM); Functional Assessment of Cancer Therapy–Leukemia (FACT-Leu); and NCCN distress thermometer (DT). We used descriptive statistics and ANOVA to analyze results.

Results: Mean age of study participants was 59.4 (SD 13.4); 21 (49%) were female. Patients were mostly high-risk for recurrence, with 25 (58%) being ≥60 years old, 19 (44%) having high-risk cytogenetics, and 10 (23%) having relapsed disease. Among relapsed patients, the mean number of prior treatments was 2.7 (SD 1.3). At the time of this analysis, 5 patients (18%) had gone on to receive a stem cell transplant. As expected, symptoms were most prominent during the second and third weeks of treatment.  However, across all 4 weeks of induction patients consistently reported 5 symptoms at a moderate or severe level (scores of 4 to 6, or 7 to 10 out of 10, respectively), including: poor appetite (35%), dry mouth (37%), difficulty sleeping (38%), dysgeusia (44%), and fatigue (56%).  Other prominent moderate-to-severe symptoms included diarrhea (35%), daytime sleepiness (30%), and nausea (27.5%), despite standard supportive care. Mean QoL by FACT-Leu worsened substantially from week 1 (121.8, SD 27.6) to week 2 (108.2, SD 26.3), and then slowly recovered thereafter, improving to better than baseline by month 3 and continuing to improve throughout 1-year of follow-up (p<0.01; see Figure 1). The mean distress score across all 4 weeks of induction was 4 (SD 3.2), which is the threshold for recommended referral to additional support services, but was higher in week 1 (4.4; SD 3.5) compared to week 4 (3.0; SD 3.1). Grouping patients by remission status based on bone marrow assessments done between 30 and 45 days post-induction, QoL and DT scores appear markedly different, and diverge at this point (Figures 2 and 3), such that patients with persistent disease after induction have progressively worse QoL and more distress compared to patients in remission.

Conclusion: AML patients receiving induction chemotherapy face a significant symptom burden, impaired QoL, and moderate psychological distress. Several of the most prevalent and severe symptoms during induction may be amenable to further targeted intervention. Longitudinal QoL and distress scores diverge markedly on the basis of post-induction remission status, suggesting that further targeted interventions may be needed to address the greater burden of issues among patients with relapsed disease.  The overall prevalence and severity of symptom, QoL, and distress issues suggests sizeable unmet palliative care and psychosocial needs among patients with AML.

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