Long-Term Health Related Quality Of Life and Symptom Burden In Patients With Acute Promyelocytic Leukemia Treated With All-Trans Retinoic Acid (ATRA) and Chemotherapy
Authors: Efficace Fabio , Rambaldi Alessandro , Di Bona Eros , Fabbiano Francesco , Cottone Francesco , Breccia Massimo , Avvisati Giuseppe , Foà Robin , Morselli Monica , Cutini Ilaria , Rossetti Elena , Leoni Pietro , Falini Brunangelo , Romani Claudio , Di Raimondo Francesco , Mancini Valentina , D'Ardia Stefano , Martinelli Giovanni , Cassibba Vincenzo , Finizio Olimpia , Cascavilla Nicola , Carella Angelo Michele , Vignetti Marco , Mandelli Franco , Lo Coco Francesco 
Published: October 2019

Abstract

Background
The combination of all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy regimens is currently considered the standard of care for newly diagnosed acute promyelocytic leukemia (APL) patients. This combination has greatly contributed to convert APL from a frequently fatal disease to a highly curable one. However, there is lack of data on the impact of such therapies on patients’ health-related quality of life (HRQOL).

Objective
The main objective of this study was thus to investigate long-term HRQOL of APL patients previously treated with ATRA plus anthracycline-based chemotherapy. The physical and mental HRQOL profile of these patients was compared with that of matched control subjects from the general population to identify specific areas most in need of attention in long-term follow-up care. A secondary objective was to outline symptoms’ burden from the patients’ perspective.

Patients and Methods
Data were gathered through an ongoing multicenter survivorship study that recruits APL patients previously enrolled in two large GIMEMA trials (i.e., AIDA0493 and AIDA 2000). In both trials, APL patients were treated with ATRA plus Idrarubicin (AIDA). The main inclusion criterion was having survived the initial diagnosis for more than 5 years and being in complete remission (CR). Generic HRQOL was assessed with the SF-36 that 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). All scales ranged between 0 and 100, with the higher scores representing better outcomes. Clinical significance was evaluated and eight points were considered to be a minimally important difference for the eight SF-36 scales. Mean SF-36 scores were compared to available national general population reference values (i.e., 1997 subjects without cancer) and all analyses were adjusted for age and gender. Symptom burden was assessed according to the M.D. Anderson Symptom Inventory (MDASI). Symptom severity was assessed for the following symptoms: fatigue, pain, sleep disturbance, drowsiness, poor appetite, shortness of breath, nausea, vomiting, dry mouth, numbness, difficulty remembering, distress and sadness. All items were rated on a numeric rating scale from 0 to 10, with the higher scores indicating a higher level of symptoms. These were categorized as “mild” (ratings between 0 and 3) and “moderate to severe” (ratings between 4 to 10).

Results
Analysis is based on 136 adult APL patients who agreed to participate. At study participation, the mean age of patients was 52 years (55% males and 45% females) and the median time from diagnosis was 13 years (range: 4.5-20). Age and gender adjusted comparisons between APL patients and the general population norms revealed worse outcomes for the following scales: RP (P&lt;.001) and RE (P&lt;.001). Such differences were more than six times the magnitude of a clinically meaningful difference (i.e., at least 8 points), respectively for the physical (Δ=51 points) and the emotional scales (Δ=49 points) of the SF-36. Analysis within our patient cohort revealed that older APL patients (i.e., those aged more than 52 years) had a statically significant lower physical functioning (P&lt;.001) and higher pain severity (P=.0448) than younger ones. Investigation of the HRQOL profile of patients by trial participation (i.e., AIDA 0493 vs. AIDA 2000) or time since diagnosis (cut-off median time of 13 years) revealed no difference in all scales of the SF-36. Fatigue was the most burdensome symptom being reported as moderate to severe in 35% of patients. Other frequently reported moderate to severe symptoms were: difficulty in remembering (30%), sadness and distress (29%).

Conclusions
Although ATRA plus anthracycline-based chemotherapy regimens have greatly increased cure rates in APL, the HRQOL of these patients is heavily affected by the consequences of the disease and treatment, that persists many years after diagnosis and treatment.

Disclosures:
No relevant conflicts of interest to declare.