Health Related Quality of Life of Long-Term Survivors of Acute Promyelocytic Leukemia Treated with All-Trans Retinoic Acid and Chemotherapy

Background:

Combined treatment with all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy regimens has remarkably contributed to improve treatment outcomes in patients with Acute Promyelocytic Leukemia (APL) patients leading to cure rates above 80%. However, information is lacking on how these patients might recover in the long-term period.

Objective:

The primary objective of this study was to investigate long-term health-related quality of life (HRQOL) and symptom burden in APL and to examine factors predicting better long-term HRQOL outcomes.

Patients and Methods:

Patients with APL treated within two large GIMEMA trials (i.e., AIDA0493 and AIDA 2000) were considered. All patients received ATRA plus Idarubicin (AIDA) for induction followed by consolidation that was risk-adapted in AIDA2000 and in most cases, maintenance for 2 years . The main inclusion criterion was having survived the initial diagnosis for more than 5 years and being in complete remission (CR) at the time of study inclusion. The SF-36 was used to assess generic HRQOL. This questionnaire consists of 36 items covering eight generic health status/QoL domains: physical functioning (PF), role limitations due to physical health (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social functioning (SF), role limitations due to emotional problems (RE) and mental health (MH). Mean SF-36 scores were compared between APL patients and those from general population. To minimize bias, all comparisons were performed between APL patients and corresponding propensity score-matched peers from general population, further adjusting for education, family status and geographical area using a multivariate linear mixed model. For descriptive purposes, a cut-off of 30 years was considered to distinguish between younger and older patients at the time of diagnosis and the corresponding HRQoL profiles were compared using multivariate linear regression analysis to adjust for key potential confounders. Also, M.D. Anderson Symptom Inventory (MDASI) was assessed to investigate the profile and prevalence symptom burden

Results:

Of the 307 patients, potentially eligible for this analysis and invited to participate in the study, 244 completed a HRQOL questionnaire (compliance 79.5%). No differences were found in the main socio-demographic and clinical characteristics between patients with or without a HRQOL evaluation. Mean age of patients was 52 years (range 20-90) and there were 47% males and 53% females. Median time from diagnosis was 14 years (range: 4-20). There were 81% of patients reporting at least 1 comorbidity at the time of HRQOL evaluation. APL long-term survivors reported a HRQOL profile broadly similar to that of their peers in the general population. However, the RP scale was statistically (P=0.016) and clinically meaningful worse in APL patients. Fatigue was the most prevalent symptom with 70% of patients reporting it with any level of concern, as well the most frequently reported moderate to severe symptom by 29 % of patients. Being distressed and problem with remembering things were the other two most prevalent symptoms reported by 65% and 62% of patients respectively. Being diagnosed at a younger age (<30 years) was a key factor associated with better long-term HRQOL outcomes. This was particularly relevant in physical health aspects. Detailed results of adjusted mean differences in SF-36 scores between age groups are reported in Table 1.

Conclusions

APL patients successfully treated with AIDA-like regimens may expect to have broadly similar HRQOL outcomes when compared to their peers witout cancer in the general population. However, significant limitations in work or other daily activities due to physical and emotional problems still persist after many years from diagnosis in the majority of patients. Our results also show that on the long-term period, younger APL patients recover better than older ones in terms of HRQOL outcomes.

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