A summary of the number of articles identified from the search strategy, the reasons for publication exclusion, and total number of publications included is presented in Fig. 1. Publications and study design details of all included studies are presented in Appendix Table 1.
Key demographic and clinical characteristics of the included study populations can be found in Table 1. The sample size of included studies ranged from 8 to 481. The study populations primarily comprised of middle-aged adults; two studies reported mean age below 40 years of age [13, 14], and three studies had a mean age above 65 years of age [15–17]. Five studies reported the distribution of AML disease origin at baseline; study populations were primarily comprised of primary AML patients (range: 54.5–100.0%). No individuals with refractory AML were identified in the included studies.
The most frequently utilized HRQoL instrument was the cancer-specific EORTC QLQ-C30 questionnaire (50.0%, Table 1); generic HRQoL instruments (EQ-5D and SF-36 or SF-12) were utilized in only 35.7% of included studies. Descriptions of the included instruments, including measured domains and interpretations of scoring, can be found in Appendix Table 2.
Global Assessment of HRQoL
Eleven studies (78.6%) reported a global assessment of HRQoL. Ten studies (71.4%) utilized a cancer or leukemia-specific instrument; of these, six studies measured global HRQoL in patients who were survivors of AML, including four studies with participants who had achieved complete remission at the time of assessment. The mean global HRQoL scores in AML survivors and patients with active AML are presented in Tables 2 and 3.
An improvement in HRQoL was generally shown among survivors compared to active AML patients using the FACT-G and EORTC QLQ-C30 instruments: the mean EORTC QLQ-C30 scores ranged from 67.9  to 80  in survivors compared to 50  to 77.2  in patients with active AML, and mean FACT-G scores was 77.5  in survivors compared to 56.1  to 84  in patients with active AML. An exception to this trend was the FACT-G scores reported by Sekeres et al., where superior HRQoL was reported among active AML patients . The reason for this difference is unknown because of insufficient reporting of relevant clinical characteristics of the sample populations.
The EQ-5D instrument was utilized in two studies of AML survivor populations (Table 3). Leunis et al. reported an EQ-5D utility score of 0.82, and an EQ visual analog scale (VAS) score of 74.6, a significantly lower result compared to a general population sample (p = 0.0333). A separate study by Slovacek et al. reported the lowest EQ VAS score, 67.5, among individuals previously treated with autologous hematopoietic stem cell transplantation .
Three studies used the SF-12 or SF-36 scales to measure HRQoL, although one study did not report results for the AML population . One study measured HRQoL in adult survivors of childhood AML and found no difference in physical or mental scales compared to population norms . Among participants actively undergoing treatment for AML, mean SF-36 physical scale scores were approximately two standard deviations below population norms within the first 6 weeks from diagnosis, indicating a quick and sharp decline in HRQoL shortly after diagnosis; mental scores were comparable with general norm scores .
Five of the included studies (35.7%) reported HRQoL measures of functional domains using the EORTC QLQ-C30. Scores for each of the domains ranged from 75.9 to 83 (cognitive), 64.1 to 83.1 (emotional), 27 to 74.8 (role), 67 to 86.7 (physical), and 56 to 83 (social) at baseline. Score ranges were similar between individuals with active AML and AML survivors in the cognitive, emotional, and social domains. Poorer scores were observed among individuals with active AML compared to AML survivors in the role domain—ranging from 27 to 67 vs. 72.5 to 74.8, respectively—and the physical domain—ranging from 67 to 73 vs. 80.4 to 86.7, respectively.
A comparison of mean scores between AML survivors and a general population sample found significantly lower scores reported across all functional domains in the AML population .
Symptom Domains and Financial Difficulties
Symptom-specific domains were included in six instruments, five of which were cancer or leukemia specific (Table 4). The most frequently used instrument to measure symptoms was the EORTC QLQ-C30, which includes three symptom scales—fatigue, nausea/vomiting, and pain—several single items assessing symptoms commonly reported by cancer patients, and perceived financial impact of the disease (Appendix Table 1).
Across studies, the most affected domains were fatigue, pain, dyspnea, insomnia, appetite loss, financial difficulties, and anemia (Table 4). Active AML patients reported appetite loss and fatigue symptoms as having the most detrimental impact on HRQoL, whereas fatigue and insomnia had the worst impact on HRQoL among AML survivors. One study comparing AML survivors to a general population sample identified a statistically significant negative impact on AML survivors in the fatigue, pain, dyspnea, and appetite loss domains (p value <0.05 for all comparisons) and a clinically relevant impact—defined as a difference of at least ten points—in the fatigue and dyspnea domains .
Perceived financial difficulties showed negative impact in both active AML patients and AML survivors and were reported to be significantly worse in AML survivors compared to a general population sample (p value <0.05) .
A single study utilized the leukemia-specific EORTC QLQ-Leu instrument among adult AML survivors; the subscales with the highest percentage of survivors reporting problems included graft-versus-host disease (GVHD; 86%) and infection susceptibility (51%), although the authors noted that few participants scored these symptoms as severe .
Four studies were prospective in design, providing a temporal perspective of symptoms during and after AML chemotherapy, with a follow-up period ranging from approximately 6 to 39 weeks. Of the four studies, three [13, 15, 17] assessed HRQoL beginning at diagnosis, while the fourth study measured HRQoL at the end of patients’ induction therapy and followed patients for 9 months post-induction .
In the majority of the studies, short-term trends—from diagnosis to week 10—depict a rapid worsening of HRQoL across all domains shortly after diagnosis, followed by a gradual increase in HRQoL from week 2 to 6 (Fig. 2; Appendix Figure 1). Exceptions to this trend were reported by Moller et al., where the poorest HRQoL scores were observed at baseline, followed by consistent improvements in functional and symptom domains over time. This observation is likely due to the lack of an assessment following induction through to week 12. Symptom and functional domains reported similar short- and long-term trends (Appendix Figure 1).
HRQoL by AML Subgroup
A single study reported HRQoL of relapsed AML survivors; no information of refractory participants was identified. HRQoL in relapsed participants was worse than in non-relapsed participants (EORTC QLQ-C30: 72 vs. 76; EQ-5D utility: 0.8 vs. 0.8; and EQ-VAS: 73 vs. 75) . These differences were not reported to be statistically significant, although this could be due to the small sample size of relapsed participants (n = 17) .
Applying the quality assessment checklist outlined by Jacobs et al. , only two studies (14.3%) [15, 18] were deemed robust (Appendix Table 3). When scoring question four of the checklist—use of a validated, disease-specific questionnaire—only leukemia-specific tools were deemed acceptable to meet this criterion. Relaxing this requirement to include both leukemia- and cancer-specific tools resulted in five (35.7%) studies designated as robust [15, 18, 19, 22, 23]. The remaining studies were not deemed robust [13, 14, 16, 17, 20, 21, 24–26].