Quality of life considerations in myelodysplastic syndrome: not only fatigue

KEYWORDS:

• Myelodysplastic syndrome (MDS)
• quality of life (QOL)
• sleep
• physical exercise
• lifestyle
• psychology
• clinical treatment

1. Introduction

A recently published paper in this Journal by Liu [1] et al. focused on determining factors impairing quality of life (QoL) beyond fatigue [2,3] in patients with myelodysplastic neoplasm (MDS) [4]. The issues addressed by the authors also stimulate our reflections and significantly contribute to our understanding of MDS and its impact on QoL.

Disease overview and QoL of MDS patients. MDS is a group of hematological malignancies characterized by bone marrow failure and a variable risk of progressing into acute myeloid leukemia (AML) [4]. Genomic profiling has revealed molecular alterations and their relation to disease pathogenesis and clinical phenotypes in patients with MDS [4]. Significant advancements in the field of MDS, particularly in diagnosis, classification, prognostication, and decision-making, have led to a more hopeful outlook for patients. Despite most MDS remaining incurable and unsuitable for allogeneic stem cell transplantation, these advancements cause optimism.

Therefore, the primary objective of clinical management for patients with MDS is to maintain and improve their health-related quality of life (HRQoL) [2]. This multidimensional concept encompasses physical, role functioning, social, and psychological aspects of well-being, which significantly impact the QoL of individuals with MDS. Patient-reported outcomes (PROs) are instrumental in evaluating HRQoL in clinical trials and real-world practice [2]. In the latter, regular HRQoL assessments, including PRO evaluations as part of routine medical training, can assist physicians in enhancing the quality of care, making informed treatment decisions, and identifying unmet needs beyond the clinical outcomes of MDS patients [2,3].

Table 1 shows some MDS-unspecific instruments to measure PROs in this setting [2], among which, the EORTC QLU-C10D was more accurate than the EQ-5D-3 L in discriminating between clinically known MDS groups [5], as reported by a recently published a study involving 619 patients with MDS [5]. Nowadays, two tools (Table 2) (comprehensively reviewed in reference 2), such as the 33-item QoL in the Myelodysplasia Scale (QUALMS) and the 29-item QoL E (QOL-E), have been validated to measure HRQoL in patients with MDS precisely. These tools are scored from 0 (indicating worst HRQoL) to 100 (indicating best HRQoL). A significant change in the QUALMS score is between 5 and 10 [2]. In this category of patients, HRQoL may be impaired during the entire disease course, from the onset to the advanced phase, and aggravated by treatments, first of all, the regular transfusion needs [2].

Table 1. Two MDS-specific HRQoL scoring systems°*: QUALMS and QOL-E.

QUALMS	QOL-E
• QUALMS-P (physical burden) (14 items: tiredness, effect of low energy on schedule, weakness, inability to participate in activities, fatigue, worry about becoming a burden, hopelessness, bowel changes, shortness of breath, change in long-term plans, concentration issues, effect of healthcare on life, nausea, lack of energy)	• General perception of well-being (2 items: currently, compared to 1 month ago) • QOL-FIS (physical well-being) (4 items: heavy activities, climbing stairs, lowering self, self-care)
• QUALMS-BF (benefit finding) (3 items: grateful for tomorrow, quality information, gratitude when used to take for granted)	• QOL-FUN (functional well-being) (3 items: got little done, fatigue when working, napping)
• QUALMS-E (emotional burden) (11 items: could not do anything about the disease, unpredictability, no concrete answers, no clear information, fear of death, difficulty explaining MDS to others, progression worries, test result worries, anger, infection worries, limited emotional support)	• QOL-SOC (social/family well-being) (4 items: interference with life, oppressed by disease, burden to family, effect on retaining job)
• Other (5 items: family relationships strained, bruising, crowd avoidance, bleeding worry, financial worry)	• QOL-SEX (sexual well-being) (2 items: effect on sex life, sexual excitement) • QOL-FAT (fatigue) (7 items: effect on chores, how much fatigue, headaches, palpitations, disturbance of self-care difficulty, the effect of being bed-ridden, sleep quantity)
	• QOL-MDSS (MDS-specific) (7 items: shortness of breath climbing stairs, transfusion dependence, ability to do chores, ability to travel, dependency on healthcare, stress/worry, treatment side effects)

°Taken and adapted from [2]. *Reviewed and referenced in [2]. HRQoL = Health-related quality of life; MDS = Myelodysplastic syndromes; QOL-E = Quality of Life E; QUALMS = Quality of Life in Myelodysplasia Scale.

Table 2. Some MDS-unspecific HRQoL scoring systems: cancer-specific (EORTC QLQ-C30; FACT-An), hematology-specific (HM-PRO), and generic (SF-36, EQ-5D) tools°*.

EORTC QLQ-C30*	FACT-an*	HM-PRO*	SF-36*	EQ-5D*
• Function	• FACT-G	• Impact	• Physical functioning	• Mobility
Physical (5 items)	Physical well-being (7 items)	Physical behavior (7 items)	• Social functioning	• Self-care
Emotional (4 items)	Functional well-being (7 items)	Social behavior (3 items)	• Physical role functioning	• Usual activities
Role (2 items)	Social/family well-being (7 items)	Emotional behavior (11 items)	• Vitality	• Pain/discomfort
Cognitive (2 items)	Emotional well-being (6 items)	Eating and drinking habits (3 items)	• Bodily pain	• Anxiety/depression
Social (2 items)	• Fatigue a (13 items) ^	• Signs and symptoms (18 items)	• Mental health
• Symptoms	• Non-fatigue items relating to anemia (7 items)		• Emotional role functioning
Fatigue (3 items)			• General health perceptions
Nausea and vomiting(2 items)
Pain (2 items)
Dyspnoea (1 item)
Sleep disturbance (1 item)
Appetite loss (1 item)
Constipation (1 item)
Diarrhoea (1 item)
Financial impact (1 item)
• Global QoL (2 items)

°Taken and adapted from reference [2]; *All the reported systems were reviewed and referenced in [2]. EORTC QLQ-C30 stands for European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, EQ-5D for 5-item European Quality of Life Five Dimensions, FACT-An for Functional Assessment of Cancer Therapy-Anemia, FACT-F for Functional Assessment of Cancer Therapy-Fatigue, FACT-G for Functional Assessment of Cancer Therapy-General, HM-PRO for hematologic malignancy patient-reported outcome, HRQoL for health-related quality of life, MDS for myelodysplastic syndromes, and SF-36 for 36-item Short. HRQoL = Health-related quality of life; MDS = myelodysplastic syndromes; QoL = Quality of life; SF-36 = 36-item Short Form. The FACT-F^ score includes the 28 FACT-G items and the 13 fatigue items.

At initial presentation, many patients with MDS experience a significant symptom burden, as reported by a recently published study, which included 927 patients, of which other than 50% suffered from clinically essential problems related to physical functioning and dyspnea at the onset of MDS [3]. Of note, the most prominent and severe symptom afflicting MDS patients is chronic fatigue, which has a strong negative association with HRQoL [6]. This subjective complaint prevails in anemic patients and is the most prominent clinical manifestation of MDS [1–3]. It is related to several deviations in physiological homeostasis as well as with negative psychological consequences, which, in turn, may aggravate chronic fatigue [6]. Moreover, other possible contributors to chronic fatigue in patients with MDS may be chronic inflammation, immune dysregulation [4], reduced physical mobility, and relative functional deconditioning [6]. Along with chronic fatigue, patients with MDS also report other complaints that affect their daily lives, such as pain, discomfort, restricted mobility, difficulty with self-care activities, and mood disturbances like anxiety and depression [7,8]. All of these concerns contribute to the patient’s overall frailty and vulnerability, which can lead to physical and psychological impairments, difficulty walking as well as functional deterioration, and ultimately, loss of personal autonomy [8,9]. These challenges are not unique to patients with MDS. Still, they can exacerbate specific HRQOL issues in this almost frail patient population, whose burden of illness may increase in the presence of competing comorbidities and the occurrence of treatment side effects. Therefore, a comprehensive evaluation of the HRQOL in the MDS setting is necessary to identify and address patients’ diverse concerns that affect their QoL.

In this regard, a paper recently published by Liu and colleagues [1] has addressed these essential topics, stimulating reflections on this issue. The authors reviewed literature from the past 30 years to examine the factors impairing the functional status of patients with MDS. Therefore, they aimed to shed light on the impact of clinical treatments, lifestyle factors, functional status, and symptoms experienced by patients with MDS, highlighting several areas that are susceptible to appropriate interventions, thereby enhancing the management of these patients and improving their QoL.

Among the topics they have addressed, sleep disorders negatively impact the survival of patients with MDS [1,10]. Indeed, in patients with MDS, these disturbances can be exacerbated by certain disease features, such as anemia, bruising/bleeding, night sweats, bone pain, fever, and repeated infections. The disruption of the body’s natural sleep cycle can lead to mood alterations and cognitive impairment, which can heavily impact QoL patients with MDS [1,10]. Furthermore, living with a chronic and incurable illness like MDS can be emotionally challenging due to concerns about the progression of the disease, uncertainty about the future, and the impact of symptoms on daily life. Of course, these concerns may lead to increased levels of anxiety and depression [1].

Again, nutritional alterations and body mass disorders are other critical issues to take into account in patients with MDS [1,11–13]. Indeed, nutritional problems are common in patients with MDS and are mostly related to the disease and its treatments. These issues can directly impact patients’ compliance with lifelong treatment and overall survival and QoL [11]. In this view, obesity and malnutrition may cause differences in drug levels, distribution volume, and elimination, making therapeutic agents potentially more toxic. In addition, malnutrition may predispose patients to invasive diseases and weakened immunity, potentially resulting in a higher incidence of clinical complications. With this regard, literature data deal with a negative relationship between low pre-treatment geriatric nutritional risk index [12], skeletal muscle depletion impact [13], and the poor tolerability of azacitidine in malnourished patients with MDS. Interestingly, lifestyle therapies are becoming more critical in managing MDS, taking a holistic approach. In particular, there is a growing interest in physical exercise to improve these patients’ well-being [14]. Unfortunately, from diagnosis, physical activity and exercise levels tend to decline significantly in patients with MDS, reducing muscle tone and walking ability [10,14]. With this regard, physical exercise can be a useful therapeutic and practical measure to improve the functional status and the QoL of patients with MDS. When designing exercise plans, it is essential to consider the patient’s disease and treatment history, level of functional impairment, and any comorbidities. These plans should be specific to the patient’s peculiar needs and abilities, and skilled guidance is sought throughout the individualized program [14]. Therefore, addressing particular complaints, other than fatigue, is crucial when managing patients with MDS to preserve and improve their QoL [1].

3. Expert opinion

The article authored by Liu [1] and colleagues sheds light on the various physical and psychological symptoms, as well as lifestyle issues that typically affect patients diagnosed with MDS. It explains how these problems impact their QoL. To manage and improve the well-being of patients with MDS, healthcare providers must pay close attention to these complaints and provide timely intervention and support [1,2]. Therefore, a multidisciplinary approach should address effective global disease management, which includes counseling, appropriate pharmacological interventions, physical exercise, and measures to support behaviors and cognitive functions [9]. With this regard, geriatric assessment, although not always feasible in real-world clinical practice, should become a standard of clinical evaluation in patients with MDS [15], allowing for better prediction for survival and treatment toxicity [15], taking into account patient-related factors such as comorbidity, disability, frailty other than fatigue [15]. Therefore, healthcare providers can provide significant benefits in managing patients with MDS by addressing their subjective concerns, other than the disease and its related major complaint, such as fatigue, and adopting appropriate solutions.

In conclusion, managing MDS syndrome requires a holistic approach, considering physical, emotional, and social dimensions. While fatigue is the most prominent symptom of MDS, it is essential to recognize and address the broader challenges that affected individuals face with this disease. By implementing comprehensive care strategies, including psychosocial support, coping mechanisms, home care facilities, and palliative care when needed, healthcare providers can significantly enhance the well-being of patients living with MDS.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.