To our knowledge, this study contributed to the literature on the comprehensive identification of central symptoms and central SCs in adult AML patients receiving chemotherapy by conducting NA and then investigating the interrelationships among central symptoms and central SCs, which can help researchers and clinical staff design precise personalized and scientific management strategies for symptoms and SCs.
In adult AML patients receiving chemotherapy, worrying was the most severe symptom, and feeling sad was the central symptom; these findings are somewhat dissimilar to those of previous research. For example, Fang et al. 33 indicated that pain was the most severe symptom and that worrying was the central symptom in children with AL during chemotherapy using the MSAS 10–18 (n = 469). Using the MDASI, Zhu et al. 34 showed that fatigue was the most severe symptom and that sadness had the largest strength and closeness values in cancer survivors (n = 1065). These discrepancies may be due to differences in the individuals included, assessment methodologies, tumor features, and treatments 19,35. Our study also revealed that, due to variations in metabolic and other physiological and psychological characteristics, adults with AML receiving chemotherapy experience symptom burdens that differ from those of children with AL. Moreover, the numbers and types of assessment items in the MDASI are dissimilar to those in the MSAS and MSAS 10–18. Finally, sex, age, time since diagnosis, chemotherapy regimen, chemotherapy phase, and clinical classification were important factors influencing the symptom burden.
Based on our findings and previous studies, we concluded that psychological symptoms, including feeling sad, worrying, feeling nervous, panic, depression, and anxiety, were central symptoms for patients, affecting other symptoms negatively. 17,36,37 These findings imply that clinical staff and researchers should understand the psychological states and cognitive processes of AML patients receiving chemotherapy. Additionally, it was reported that mindfulness-based interventions, meaning-enhancing interventions, dignity therapy, life review, and aromatherapy could relieve the psychological burden of patients and promote positive moods, which may be essential for the emotional management of adult AML patients 34,38.
Three SCs were derived from the data, namely, the neuropathy SC (dizziness, lack of energy, difficulty concentrating, feeling drowsy, sweats, and pain), nutritional SC (change in the way food tastes, lack of appetite, weight loss, feeling irritable, and dry mouth), and psychological SC (worrying, feeling sad, and feeling nervous). Additionally, we found that the neuropathy SC was the central SC in adult AML patients receiving chemotherapy. Our study is limited by its dissimilarity to previous studies. According to longitudinal studies throughout chemotherapy cycles, Li et al. 39 reported that the neurological SC (feeling drowsy, tingling hands or feet, headaches, and dizziness) was the most stable SC in children with AL using the MSAS 10–18. Using a twenty-symptom list, Rha et al. 15 reported that fatigue, difficulty concentrating, and drowsiness formed a stable SC in cancer patients, and fatigue was the most central symptom with the highest strength value. Furthermore, regarding the neuropathy SC, we concluded that a lack of energy (fatigue) was the most common symptom and the second most severe and distressing symptom; this symptom can be encountered at any stage of AML and is not alleviated by adequate sleep or rest. Loss of energy may also predict other symptom conditions, as it is linked to a variety of physiological symptoms/factors, such as anemia, malnutrition, pain, sleep disturbance, and decreased immune function, as well as psychological symptoms, such as worrying, depression, nervousness, and sadness 39–41.
We also discovered that the loss of energy could improve after being neglected over time when noticeable symptoms such as pain, sleep disorders, lack of appetite, worrying, and sadness develop and worsen during chemotherapy cycles 39,42. For example, chemotherapy may trigger painful neuropathies, lead to sweating, energy depletion (i.e., lack of energy, dizziness, and difficulty concentrating), and sleep disturbance, as the body strives to recover from immature myeloid cell destruction 43. Consequently, pain, a lack of energy, sweating, and sleep disturbances commonly cooccur and are identified as the neurological SC in cancer patients.
There were interrelationships between the neuropathy SC and nutritional SC as well as the psychological SC. Additionally, numerous studies have explored inflammation, genetic polymorphisms, and the tryptophan amino acid pathway as potential etiologies of SCs 43–45. Based on animal models and clinical samples, evidence suggests that the co-occurrence of multiple neurological and behavioral symptoms, including pain, fatigue, sleep disturbance, loss of appetite, changes in the way food tastes, and depressed mood, could be a “sickness behavior” SC triggered by inflammation 46,47. Psychological stress can also dysregulate the sympathetic nervous system and hypothalamic-pituitary axis pathway, leading to increased production and release of proinflammatory cytokines such as IL-1, IL-6, IL-4, and TNF-α 48,49. A recent review by Miaskowski et al. 50 reported that nuclear factor kappa B subunit 2 (NFKB2) rs1056890 was associated with a mood-cognitive SC (difficulty concentrating, feeling sad, worrying, itching, and feeling irritable), as well as a sickness behavior SC (pain, lack of energy, feeling drowsy, difficulty sleeping, and sweating). Therefore, comprehending the mechanisms of SCs could provide useful insights for SC relationship and effective symptom management in the future.
Effective symptom management will ultimately contribute to improved symptom outcomes. For example, interventions such as slow-stroke back massage, dance, tai chi, qigong, and/or cognitive-behavioral interventions could improve nutritional symptoms. In addition, self-acupressure, cognitive behavioral acceptance, and commitment therapy may be useful for managing psychological symptoms. Finally, educational interventions reduce the suffering associated with nutritional symptoms 51–54. Further empirical clinical research should be conducted to determine whether intervention in patients with central symptoms/SCs may simultaneously decrease the burden of other symptoms/SCs.
On the basis of our study, we recommend further research focusing on various areas. First, central symptoms, bridge symptoms, and sentinel symptoms in central SCs should be identified, and the relationships among them should be explored. Then, the mechanisms underlying the aforementioned symptoms in the central SCs should be analyzed; finally, specific central SC management strategies should be developed for cancer patients.