The diagnosis of Transfusion-dependent Thalassemia (TDT) affects a child’s physical and psychological wellbeing. Understanding how the disease and treatment affects the HRQoL dimensions is imperative in improving the delivery of care beyond the clinical markers of the disease. One of the strengths of this study is the large number of patients sampled from various regions across the country. Table 2 provides an overview of the previous studies conducted on the HRQoL of TDT children in Malaysia using the PedsQL™ GCS compared to the current study. The wider geographical selection and larger sample size (n=368 from 12 different centres) in this study minimises any environmental-related factors compared to the previous studies(7-9) which focused only on the urban population and included a smaller sample size(n<100 from 1 up to 3 different hospitals). The findings of this study would be more generalizable to the other TDT paediatric patients in the country.
In this study, we found that the HRQoL scores of TDT patients were higher across all dimensions compared to the scores of similar studies conducted in Malaysia almost a decade ago as seen in Table 2. The previous studies conducted in Malaysia had recruited children with TDT aged 5-18 years old(7-9), while this study included patients as young as 3 years old. Inclusion of this younger cohort could have contributed to the higher mean scores observed, as younger patients is hypothesized to have less morbidity related to the progression of the disease and treatment as the effects of chronic transfusion has not yet manifested.
However, we believe that the free access to iron chelation therapy, especially oral chelators, improved the compliance of patients and led to higher overall scores. The delivery of care has improved over the past decade. The development of clinical practice guidelines and its distribution across the various centres provides evidence-based guidance for the management of patients(2). This has ensured that even centres who do not have a dedicated haematologist are able to plan the management of patients based on the recommended blood transfusion targets and also initiating iron chelating therapy as soon as the serum ferritin levels increases beyond 1000μg/L. Iron chelators funded by the government (23) has allowed for better access to treatment(24). Prior to 2003, less than 20% of TDT patients received sufficient iron chelation therapy and many died from complications of chronic iron overload(22). The accessibility and sustained use of subcutaneous Desferrioxamine followed by availability of oral Deferiprone in 2005, and subsequently oral Deferasirox in 2012 at no cost to patients throughout public hospitals in Malaysia have significantly decreased the morbidity and mortality related to iron overload complications. In this study approximately 70% of patients were on oral iron chelators. This progress has certainly improved the compliance to treatment, decreased the burden of pain related to the administration of subcutaneous treatment and decreased the burden of treatment related to the use of the subcutaneously administered iron chelator. In addition to that, the availability of MRI T2* scans have allowed clinicians to detect the development of iron overload in vital organs, allowing them to intensify treatment earlier and thus preventing the development of chronic iron overload complications. These factors combined has contributed to the overall improvement of HRQoL in these patients.
The Psychosocial Health Summary Score was consistently found to be lower compared to the Physical Health Summary Score in previous studies conducted in Malaysia(7-9), Thailand(10-12) or the Middle East(16, 31, 32). We found that the school functioning dimension had the lowest mean score in this study. This dimension, among others, measures the frequency of absenteeism from school either because of illness or for the reason of seeking treatment. Previous studies in various countries reported similar findings(10, 11, 17, 18, 33). Children with TDT require blood transfusions every 3 or 4 weeks and this could affect their school attendance. It is also possible that suboptimal blood transfusions received did not improve anaemic symptoms which could disrupts a child’s ability to concentrate in class. However, parameters regarding optimal blood transfusion was not collected in this study to verify if there was a correlation. There is scarce information on whether patients tend to score lower in this dimension because of anaemic symptoms leading to poor performance in school or because of absenteeism from school caused by frequent hospital visits. This is an area worth researching as a patient’s schooling performance may affect their future employment prospects and ability to contribute to society. Meanwhile, lower emotional and social scores can be attributed to the physical changes and limitations in activity brought about by the severe anaemia, impacting self-esteem, body image, involvement in physical or social activities and possibly future employment(34). Psychosocial well-being is a modifiable factor. A patient’s well-being can be further improved with specialized counsellors and social support groups which help patients develop coping mechanisms as recommended in guidelines(1). Treatment geared towards the prevention of psychological issues can improve a patient’s mental health and increase their ability to comply to treatment, thus improving the physical health and overall HRQoL. Efforts of forming a multidisciplinary team consisting of parents, school officials and health care providers may benefit in improving this dimension outcome.
In this study, 5.7% of the variability of the TSS were negatively predicted by increasing age and the use of dual iron chelating agents. Predictors of a higher PHSS was being male, while increasing age and parent-proxy report were negative predictors. The use of dual iron chelating agents was a predictor for lower scores in the PCHS. In a study conducted in India by Dhirar et. al(33), 9.6% of the variability in TSS scores were predicted by age, age of onset, frequency of transfusion per month, duration of treatment, number of concomitant medicines, number of comorbidities and the total number of visits per year. In a study conducted in Thailand, 8.9% of the variability in the TSS was explained by the age and the severity of the condition. Other studies found clinical markers such as the pre-transfusion haemoglobin levels(11), frequency of transfusion(8, 10, 13) and serum ferritin levels(35, 36) to be significant predictors of HRQoL. The low R2 in this study is explained by the absence of these clinical markers.
Age was a consistent predictor across several studies(11, 33, 36). Apart from the emotional dimension, the negative correlation and coefficient between age and the HRQoL scores implies that HRQoL worsens as patients grow older. As patients grow older, the burden of treatment may increase with higher volume of blood required, onset of complications and the need for higher dosages of iron chelating therapy, resulting in lower HRQoL. This finding contrasts with the findings of Thavorncharoensap et. al.(11) and Sazlina et. al.(9) which reported that HRQoL in adolescent patients were better than their younger counterpart. The studies rationalized that as patients grew older, their independence and knowledge about the condition helped them cope better with the disease.
Although age is a non-modifiable factor, the choice of iron chelating therapy (type, route or number of agents) and the prevention of iron overload complication are areas where HRQoL can be improved. The use of subcutaneous infusions nightly may impair patients HRQoL as demonstrated by several studies(10, 11, 33). These studies demonstrated that patients on a single oral chelator had a higher HRQoL compared to those on combined therapy, which was consistent with the findings in this study. If a chelation therapy is not tolerated well by a patient, adherence to treatment would be challenging. Poor adherence leads to development of iron overload complications which will affect a patient’s physical functioning. The use of subcutaneous therapy is expected to affect the patient physically by limiting their range of activities and increasing their experience of pain and discomfort related to the administration of medicine(37).
Socially, patients may feel self-conscious to use medicines around their peers as they grow older. This may result in them withdrawing socially as they feel ‘different’ and may be emotionally affected by the routine of having to comply to their therapy(37). While the younger children, who may not have insight to understand the disease, may not cooperate during treatment. Besides, some families are not able to cope with the schedule of administering long hours of subcutaneous injection or simply cannot afford the accessories required for the administration. The current practise here is to prescribe oral Deferasirox monotherapy as first line treatment to all newly diagnosed TDT patients who require chelation therapy. With this progress, we expect that the overall HRQoL will improve and the risk of developing iron overload complications would be minimised. Caregivers & patients should be included in the decision-making process with the health care provider regarding the choice of iron chelator to ensure that the patient is able to adhere to the therapy and the quality of life is not compromised by the therapy.
Study Limitations
This study has few limitations. First, it was not compared to a healthy population of children in Malaysia hence making it difficult to truly estimate the impact of the disease on HRQoL. Secondly, most of the survey was completed by a proxy, as some patients were too young to answer themselves. Since proxy-reported surveys may either underestimate or overestimate HRQoL(8, 13, 18), interpreting findings from this study should take that possibility into account. Thirdly, due to time constraint and the variation in documentation of medical records across the centres, it was a challenge to obtain other clinical parameters such as the serum ferritin and the pre-transfusion haemoglobin level, which could have been used to assess the relationship between clinical outcomes and HRQoL.