Palliative care interventions and their early integration in the management of older adults with acute myeloid leukemia: a narrative review

Introduction

Rationale/background

Approximately a decade has passed since one of our editorials in this journal addressed end-of-life (EOL) care issues and the insufficient application of palliative care (PC) for patients with blood-related malignancies (1). Over the past decade, significant advancements have been made in these areas (2). However, the encouraging progress recorded in this particularly challenging setting has only partially resolved many concerns in the relationship between malignant hematology and PC (2-4).

Objectives

This narrative review focuses on a key hematological neoplasm, such as acute myeloid leukemia (AML) (5,6), which can be considered a framework of the current challenges concerning the role of PC in the setting of hematology, including healthcare practice (7-11) and clinical research (12-16). We present this article in accordance with the Narrative Review reporting checklist (available at https://apm.amegroups.com/article/view/10.21037/apm-25-32/rc).

Methods

The study employed an unsystematic narrative review to gather and synthesize the literature on EPC in the AML context. The review process is described in Table 1. A systematic search, using the PubMed database and focusing on peer-reviewed publications and reports in English published between January 2010 and June 2025, was conducted in two phases: phase 1, March–April 2025; phase 2, June 2025. For this purpose, we used pertinent keywords, such as AML, EPC, EOL care, PC, QoL, and symptom relief, among others, as outlined and reported in Table 1.

AML: an overview

AML is a blood malignancy derived from hematopoietic stem cells (6). It is more frequently occurring in older adults (5,6) with an incidence rate of up to 4 per 100,000 people; however, it is projected to rise significantly in the future (17). AML is a difficult-to-treat neoplasm characterized by the rapid proliferation of abnormal cells, which impairs hematopoiesis and results in various clinical symptoms, including anemia, an increased tendency for hemorrhage, and susceptibility to infections (6). The disease portrays a poor prognosis and high rates of morbidity and mortality in the most affected patients, with a 5-year overall survival (OS) rate of less than 30 percent for newly diagnosed (ND) AML patients (6) and much less for those with refractory/relapsed (R/R) disease (6,18). Moreover, AML involves considerable healthcare resources, which are expensive because of prolonged hospitalization, clinic visits, and supportive care demands (19,20). For AML patients, the primary goals of treatment have traditionally been achieving complete remission (CR) and OS. Thus, over the past 50 years, AML patients suitable for intensive chemotherapy (ICT) for remission induction have received it, regardless of whether allogeneic hematopoietic stem cell transplantation (HSCT) is employed as consolidation (6,21,22). According to the 2022 European Leukemia Net criteria, CR rates following ICT in AML patients are 73% in good-risk patients, 66% in intermediate-risk patients, and 45% in poor-risk patients (21). Additionally, the 5-year progression-free survival (PFS) rates are 52%, 32%, and 16%, respectively, while the 5-year OS rates are 55%, 34%, and 15% for the corresponding groups (21). These findings demonstrate significant improvements over past therapeutic results and also show that ICT effectively increases the CR rates, PFS, and OS of patient groups of all ages (6,21). However, there is still room for improvement in treating AML to enhance long-term outcomes (14,21,22), particularly for older patients who are often unsuitable for ICT (5,14,23,24) and for those with relapsed or refractory disease (15,21,25). Indeed, in most older people with AML, the patient’s comorbidities (26) and compromised fitness status (27-29) often preclude older adults from being eligible for ICT and, sometimes, represent a significant barrier to delivering lower-intensive therapies (LIT) (30,31). In this regard, a comprehensive geriatric assessment evaluating several dimensions of health before the onset of treatment, including comorbidity burdens, cognitive functions, physical ability, and emotional health factors, can establish the ability of patients to tolerate ICT or LIT approaches (29). Thus far, fitness assessment in patients with AML is crucial for delivering the appropriate therapy to the right patient, also in light of the increasing development of novel agents that have expanded the spectrum of available LIT options, adding complexity to the fitness assessment (32,33). Therefore, currently, some challenges on when to use ICT or not in older adults persist (34); however, the availability of a new and less toxic formulation, such as CPX-351, of traditional standard ICT (3+7 regimen) (35), as well as LIT, like the therapeutic association of azacytidine to venetoclax (VENAZA) (36,37) and orally administrable agents, such as FMS-like tyrosine kinase 3 (FLT-3) (38) and isocitrate dehydrogenase (IDH) (39) inhibitors, and, for LIT-unfit patients, decitabine and cedazuridine (40), have provided significant advancements in this field (31). These therapies significantly expand the therapeutic armamentarium and reduce the number of patients who are unsuitable for any causal treatments, being them candidates for best supportive care (BSC) as the only possible option (5). However, these novel treatments have improved clinical outcomes but also increased the complexity of therapeutic choices in a difficult-to-treat setting characterized by a poor prognosis, requiring timely and complex decision-making, as well as urgently needed interventions, which pose significant uncertainty and further emotionally troublesome concerns for patients and caregivers (41-53). Patients and physicians alike believe that the latter has the most influence in decision-making, even when their priorities don’t always align (41,45). Moreover, therapy-related side effects may negatively impact the quality of life (QoL), as patients may encounter a distinct range of adverse event profiles with standard ICT (54-56) as well as with novel treatments (57). Indeed, complications such as tumor lysis syndrome and infections due to prolonged and severe cytopenia linked to venetoclax (36,37), differentiation syndrome from FLT-3 (38) and IDH (39) inhibitors, as well as corrected QT prolongation associated with the latter, are examples of serious or life-threatening therapy-related complications and troublesome concerns for patient’s QoL (46,57). Consequently, patients face the difficult decision of pursuing extended OS at the risk of increased hospitalizations and suffering without a cure in most cases (32). On a converging note, hematologists must similarly critically consider whether the projected benefits of novel targeted therapies and their safety profiles align with patients’ values, preferences, and preferred QoL over an unpredictable OS that engages the patients in decision-making (42,45,46). It is challenging to determine the best strategy for older patients, as they play a significant role in developing a care plan to achieve optimal outcomes. Rather, this option would consider the patients’ status and desires as well as the pros and cons of the treatment (54). In this regard, patients want to be involved in treatment decisions, and the greater the patient involvement, the higher the patient-reported quality of care and satisfaction. Although patient value is universal, healthcare providers can help bridge the gap between the desired and actual levels of patient involvement in their treatment decisions. Attending to what patients have to say and their expectations of clinical and QoL outcomes is crucial in tailoring the best treatment plan (46,51-55) to address serious and complicated course of AML that portrays severe symptoms and emotional distress, frequent and sometimes prolonged hospitalizations as well the need of intensive PC potentially required as these suffering individuals and their caregivers approach the EOL (58-60). Therefore, PC for patients with AML is an essential part of treatment, not just for those with advanced illness or when curative options are no longer available, but also, perhaps most importantly, from the onset and during the entire course of the disease (60-65), comprehensively addressing their physical and psychosocial needs (Table 2) as well as QoL issues (55,60,66-70).

The symptom burden and its management throughout the AML trajectory

After an AML diagnosis, patients face tough decisions on treatment, life reorganization, and priorities for themselves and their families, which can cause stress and discomfort (71,72). The AML presentation varies widely, with a diverse symptom profile. Patients with ND AML face a sudden, life-threatening condition requiring immediate adaptation and urgent hospitalization to start treatment (41). Older patients may experience more ICT complications, which require adaptation of treatment based on physical status, balancing the trade-off between aggressive therapies and supportive care (5,30). Such a resultant therapeutic dilemma can be frustrating to patients (41) and caregivers (42-44) and needs to be addressed through a proper evaluation of individual risk factors to optimize treatment benefits and limit toxicity (46,57). Patients with AML experience severe physical and psychological symptoms, both due to their illness and frequently aggressive treatments that cause severe toxicities and side effects (5). In addition to disease-related features, such as coagulopathies, leukocytosis, and immunological and phagocytic impairments (infections), AML patients may experience several troublesome symptoms (Table 2) (73-79). Nearly half of AML patients may suffer from pain, the severity of which may range from mild in 8% to moderate in 25% and severe in up to 35% (73). However, this finding in this setting is less common than that observed in other blood cancers, like multiple myeloma and solid tumors (ST). Of particular interest, four clusters of symptoms were found in a population of AML patients: psychological, pain-fatigue-sleep, dry mouth-constipation, and nutrition-impaired. No matter the mechanisms behind cachexia syndrome in AML patients, they have two critical issues: oral and gastrointestinal mucositis, which make nutrition and nutrient intake complicated, thus making them susceptible to malnutrition (75,78). The involvement of inflammatory mediators and dysregulation of the cytokine network can worsen symptoms such as pain, fatigue, cachexia, and anorexia (80,81). AML is also not easy to manage, especially in comorbid patients who are elderly and have the risks of treatment on top of their comorbid illness (77). Supportive treatment, including red blood cell (RBC) transfusions, antibiotics, pain medications, and counseling, helps build a tolerance to treatment and preserve QoL (77). Counseling patients and caregivers regarding their psychological disturbances is also part of such interventions. Moreover, nutritional support (78) and physical rehabilitation (70) can positively mitigate the physical and cognitive deterioration (79) frequently observed in AML patients, improving mood and overall satisfaction in patients undergoing treatment (69).

EPC in AML: an overview

EPC refers to PC provided earlier in the disease process, which can enhance this approach to preserve the QoL of patients facing these challenging and life-threatening illnesses by preventing and relieving suffering through the early identification of distressing physical and psychological symptom burden (2,8-10,60-63). As the incidence of AML continues to rise, integrating EPC into standard hematological practice has become increasingly important (17). In this regard, it is essential to note that the aggressive nature of AMLs requires swift clinical interventions and presents unique challenges that complicate clinical management (58). The initial PC interventions advocate for a proactive approach, introducing a model of care that shifts towards integrating PC into curative or life-prolonging treatment pathways to enhance overall patient outcomes, including symptom relief, improved QoL, and better adherence to treatment (2,4,82). Moreover, integrating EPC with leukemia treatment improves QoL and mental health and helps patients plan for the future (8). Therefore, EPC can intervene throughout the entire AML, including HSCT (83), and can span the entire timeframe, incorporating interventions aimed at enhancing palliative, physical, and psychosocial well-being (63,77).

Randomized controlled trials (RCTs) on EPC and related issues in AML

Although the benefits provided by the early integration of PC into standard care (SC), this model of care has been challenging to implement in patients with AML who are exposed to the strongest therapies for potential cure, receiving the majority of them PC exclusively in their EOL, living the majority of its duration in acute hospitals, despite clear pieces of evidence provided by several studies in this field (7,12,13,71,84). Indeed, several pertinent RCTs and observational studies on EPC and related issues in the context of AML and malignant hematology have been conducted. A phase III trial tested the feasibility and initial effectiveness of the Emotion and Symptom-focused Engagement (EASE) intervention in AML patients. Enrolling 42 patients during a 1-month hospital stay, 22 received EASE plus SC, while 20 received only SC. Results showed EASE significantly reduced traumatic stress symptoms, pain intensity, and interference compared to SC alone. The authors concluded that EASE is a safe and effective alternative care model for AML patients (12). Another trial assessed the validity of the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) in 317 ICT-non-eligible AML patients, demonstrating that this instrument served as an appropriate endpoint for AML clinical trials and clinical monitoring in a non-ICT setting (66).

Along the same lines, patient-reported outcomes (PROs) obtained using the FACT-Leu were predictive of OS for older AML patients, for whom structured data collection during clinical practice for such individuals would be a helpful option (67). Regarding EPC in the AML setting, a multisite RCT assessed the effects of its application compared with SC in 160 patients undergoing ICT, of which 86 received integrated EPC and 74 SC alone, respectively. EPC patients reported improved QoL and less depression, anxiety, and post-traumatic stress disorders than those who have received SC alone (13). Additionally, a secondary analysis of this study was conducted. The research revealed that EPC-treated patients exhibited improvements in approach-oriented coping and a decrease in avoidant coping. The coping change mediated these intervention effects on QoL, depression, and anxiety symptoms. Additionally, 78% of the total EPC intervention effect on QoL, 66% of the impact on depression, and 35% of the effects on anxiety symptoms were accounted for by changes in approach-oriented and avoidant coping. Hence, the integration of EPC into ICT in AML patients facilitates the employment of coping strategies and the development of related skills, which is a critical component in the influence of an EPC intervention on health-related issues evaluated by PROs (71). Moreover, one study investigated whether different psychological interventions have an effect on QoL and remission rates in AML treated with ICT. For this purpose, 180 patients were randomized into one of four conditions: cognitive intervention, progressive muscle relaxation (PMR), combined PMR and cognitive intervention, or SC alone (the control group). The outcome highlighted a notable difference in QoL and most of its subscales between the intervention and the control groups. Specifically, cognitive intervention and physical medicine and rehabilitation achieved the maximum QoL benefit and cost-effectiveness (69). Again, another RCT with a focus on shared decision-making (SDM) aimed to minimize distress in patients and caregivers by following care according to their preferences. Researchers examined 300 patients aged 60 and older with non-disease-related AML, their caregivers, and 40 oncologists from four institutions. The primary objective was to reduce distress levels and determine whether SDM occurred, what patients perceived about it, and how difficult it was for them to make decisions. They found fewer conflictual decisions and less distress, and concluded that there was improved SDM in older adults with AML (51). Good communication and collaboration between healthcare team members were the highlighted theme in another study that was not exclusively among AML patients. This research involved nurses creating care plans and keeping their oncologists informed about patient involvement levels (85). Furthermore, a pilot RCT studied DREAMLAND, a psychological mobile app for patients with ND AML undergoing ICT. Patients were randomly assigned to DREAMLAND or SC. By day 20 post-ICT, DREAMLAND users had better QoL, less anxiety and depression, fewer symptoms, and higher self-efficacy than controls. Therefore, the app proved feasible during hospitalization, improving QoL, mood, symptom management, and self-efficacy (86).

Non-RCT studies on EPC for AML patients

Along with RCTs, observational studies have provided valuable insights. A study compared fatigue in AML patients at diagnosis with that of the general population. Ninety-one percent had fatigue scores at or below the median. Pre-treatment fatigue was linked to female sex, poorer performance, and lower platelet count (74). A study compared the costs, resource use, and outcomes of a home-based EPC program with hospital SC for patients with hematological malignancies (HM) who had advanced or terminal disease. The study involved 119 patients, divided into two groups: one for home care and the other for hospital care. Home patients were more debilitated and had shorter survival, but both had similar symptom burdens. Home patients received fewer weekly transfusions (1.45 vs. 2.77). The hospital had a higher infection rate (54% vs. 21%; P<0.001). Weekly inpatient care was three times more expensive than home care. Home EPC also saved costs by reducing the number of infection prevention days. The authors concluded that home EPC was cheaper and potentially cost-effective, as it reduced the number of days spent on infection treatment (7). The poor prognosis in older patients with AML despite extensive healthcare utilization was also explored in an observational study, which included 107 consecutive patients aged 70 years or older, estimating that 35% had ICT, 55% had LIT, and 10% had no AML-directed therapy. At least one intensive care unit (ICU) admission was reported in 47% of the patients, and a special PC was provided in 43% of the cases. In patients who died during the study duration, the median number of hospital days between AML diagnosis and death was 56 days. The majority of locations of death were general wards (31%) and the ICU (28%), with fewer dying in a PC unit (14%) or at home (12%) (19). Regarding EOL care, a study included 215 AML patients for PC and EOL care indicators (87) (Table 3). Sixty-one percent received EPC, with 51% having four or more indicators. All in EPC had at least one indicator, and only 2.7% had chemotherapy in the last 14 days. None were intubated, received cardiopulmonary resuscitation, or went to the ICU in the previous month. Few (4%) had multiple hospitalizations or emergency department (ED) visits. About half died at home or in hospice; over 40% received transfusions within a week of death. The 84 late-referral patients had fewer indicators, suggesting EPC led to excellent PC and low EOL therapeutic aggressiveness in AML patients (9). Goal of care (GOC) discussions were also a top priority. Through bringing together healthcare professionals, GOC meetings facilitate individualized treatment tailored to the patient’s unique needs and values, particularly in cases of complex diseases, such as AML. These conversations are worth including to enhance the quality of EOL care and have been shown to improve outcomes in patients with AML and high-risk myelodysplastic syndromes. Certain factors, including age over 60 years, previous history of HSCT, multiple health conditions, and non-white race, increase the likelihood of these discussions and participation in EOL programs. When they occur, patients are less likely to get chemotherapy in the last 90 days, have fewer ICU stays in the previous 30 days, and have fewer in-hospital deaths. Notably, the increased frequencies of GOC led to the introduction of more EOL programs (60). Another research study learned that HM patients were less likely to be referred to specialty PC and more likely to receive intensive EOL care than ST patients. The study involved 119,927 patients: 8,550 with HM and 111,377 with ST, representing 43% and 61% of all deaths from HM and ST, respectively. More ST 54% were treated in specialist units towards the EOL than 42% of HM patients. Quality EOL care was significantly poorer in HM patients, possibly because they were less exposed to PC specialists. Moreover, HM patients were less likely to have complete relief from their symptoms, as measured by the extent of specialized PC provided. They are also more likely to die in ED and less likely to have access to PC specialists, with worse quality EOL care and less effective relief of symptoms (88). Furthermore, an observational study identified predictors of QoL in AML patients, including young age, female gender, lower income, social isolation, and difficulty with activities, and highlighted items that clinicians may want to consider when organizing support (62). There has also been evidence that a positive coping response may improve the outcome for AML patients receiving treatment with EPC. To better understand this interaction. In this context, the research discovered that patients use diverse coping mechanisms, which include accepting that they are ill, reappraising illness, coping by doing, seeking divine support, and seeking social support. The diagnosis involved accepting their prognosis, the uncertainty of AML, and adaptation in lifestyle. Many patients found purpose in their experiences, valued everyday activities, and felt little distress about life. Having a support network was also key, with many individuals turning to their community or care team for help. Others didn’t feel guilty about relying on loved ones. Conversely, others struggled with adjustment, remained in denial, isolated themselves from life, or self-blamed. These results point out that every patient’s reaction to a diagnosis of AML is idiosyncratic, complete with its challenges (72). In addition, additional investigations explored how different preparations for the EOL differ across different backgrounds of cancer patients and their caregivers, paying particular attention to discussions between medical physicians and about support and arrangements (89-91). Patients often focus on pragmatic concerns, such as wills, while others have religious concerns and future planning. Healthcare employment is in short supply, and there is suspicion, with some viewing the system as flawed. Culture and religion significantly influence care, which has a direct impact on the level of care within the system. Social and internal problems can develop if unrecognized individuals or agencies deliver care. Providers have to learn to recognize each patient individually. Responses from stakeholders demonstrate trust building, skill development, and the provision of additional training. Religious and cultural beliefs are crucial factors that influence the quality of EOL care, and all patients should receive compassionate, personalized care. Modern palliative models attest to this, but professionals must learn to master confronting issues and handling patients’ lives with sensitivity (89-91). Once again, the acceptability of a palliative and supportive care intervention (PACT) by physicians was the subject of an observational study, in which researchers measured clinician uptake of the PACT intervention among older adults with AML in inpatient and outpatient settings by surveying the participating clinicians. They found six themes: attitudes and feelings, coordination, confidence, barriers, burden, and usefulness. The clinicians highly rated PACT and were influenced positively by it, which enhanced their job satisfaction (92). Several studies have investigated the topical issue of RBC transfusions in PC, particularly in the EOL phase of patients with HM (93-96). These papers deserve a separate discussion in a paragraph below because they address issues related to access barriers for patients with HM in PC systems, such as hospice and home care, particularly during the EOL phases. Finally, new challenges, such as technological advancement, i.e., machine learning (ML), may offer invaluable improvements in PC. It can potentially serve as an assistive tool for decision-making (25,53). Also, utilizing an ML algorithm, the development of a model for predicting disease stages and suggesting possible advantages in PC intervention design may be achieved at the right time (65). In addition, ML demonstrated that drug combinations tailored to the individual drugs of a given patient and the stage of the disease could provide highly effective, synergistic treatments in R/R AML, aiming to target treatment-resistant leukemic cells while maximizing the potential for clinical success (25). Therefore, ML has proved to be a breakthrough in healthcare, contributing immeasurably towards the development of PCs (25,53,65).

Barriers to palliative and hospice care in AML and strategies for overcoming them

Despite the benefits of early integration of hematological treatments and PC (Table 4), many barriers continue to hamper the full development of this innovative and advisable model of care management in the hematology setting, including AML. These barriers regard curative-oriented treatment focus, hematologists’ perceptions of when PC is warranted, and gaps in PC education (3,4,97-100). In this regard, multiple challenges hinder the quality of EOL care, including unpredictable prognoses, misconceptions about PC, and some hematologists’ reluctance to address EOL issues (1,60,91). In addition, HM patients are more likely to experience visits to the ED, hospitalizations, ICU deaths, and chemotherapy in their final month (1,2,9). As a result, many AML patients are not appropriately palliated or hospice-oriented, even with poor prognostic expectations. EPC skills in helping patients and family caregivers maintain their coping and decision-making abilities, aligned with their goals and values, remain beneficial in caring for patients. However, despite expanding knowledge in this field and the increased availability, the majority of HM patients still do not have access to the appropriate care. In addition, numerous illness-specific, cultural, and system-based obstacles hinder the integration of PC care with optimal EOL care for these patients (89-91). Gaps in training need to be filled, communication needs to be enhanced, and inter-specialty collaboration needs to be encouraged to facilitate the early implementation of PC (3,4,101). Lastly, having standardized organizational channels enables early and simultaneous incorporation of PC. An active system and conducive policies that integrate EPC with standard AML treatments improve QoL and mental health and encourage individuals to plan for their future (50). Shortages in education must be addressed, and coordination and communication among specialties must be enhanced to provide space for incorporating the EPC from AML diagnosis through to EOL hospice or home care (101-103). Communication, specifically, is an essential component of high-level, multi-staff PC teams, providing simultaneous practice and patient care and making possible issues of jargon, power, and affective tension. Leaders must foster open communication, reduce power differentials, facilitate conflict resolution, and promote emotional well-being among their teams. Strategies include meeting regularly, avoiding jargon, training, and utilizing technology. These enhancements improve outcomes, staff harmony, and family satisfaction; thus, good communication is key to providing quality PC (103). Standardized organizational channels facilitate easy, early, and concurrent integration of PC. A functioning system and conducive policies are needed to provide patients with HM with complete and quality care.

Transfusion barriers to hospice care: how to overcome them

When considering hospice, patients and clinicians face logistical, financial, and structural barriers related to supportive care, including RBC transfusions, which hinder referrals. Healthcare systems often struggle with the availability and cost of concentrated RBC and platelet concentrates, especially as these are less utilized in advanced disease stages. Again, inadequate reimbursement for transfusion-based hospice care is a significant barrier to providing high-quality EOL care to patients with hematology conditions (97-100). Physicians caring for AML patients at the late stage of life find it particularly difficult, notably in the provision of indiscriminate RBC transfusions near EOL (93-95). Remarkably, the lack of reimbursement and the lack of a PC workforce are consistently insurmountable obstacles (98-100). These concerns may manifest differently depending on the characteristics of health systems in various countries. Still, issues with accessing transfusions in hospices and home PC programs, especially in the EOL phase, exist in some form in almost every country. For some patients, insurance might not cover the extra costs of transfusions, making hospice admission more complicated for those with HM compared to those with ST (3,91,97-100). This topical issue burdened hematologic PC, such as RBC transfusion, was addressed by an observational study investigating the frequency, timing, indications, and predictors of RBC transfusion during home care. Among 1,108 patients, 179 (16.2%) received a transfusion at home on at least one occasion. Moreover, 52% had received RBC transfusions less than four weeks before death. The timing of care was linearly related to the patient’s survival duration after the last transfusion. Although such treatment is questionable, many patients were transfused late in their lives (93). Therefore, HM patients also rely on transfusions, which are a significant burden for both patients and caregivers. Home blood transfusions would be less burdensome, but they are not used enough. Researchers conducted a qualitative survey of 29 respondents, comprising 20 patients and nine caregivers, to assess their opinions on a home blood transfusion program. The respondents shared their positive experiences with transfusions conducted face-to-face, noted the difficulties caregivers encounter, expressed their views on home transfusions, and indicated their willingness to participate (95). A separate online survey of 320 clinicians from five hospitals also explored the barriers to referrals for these services. Out of 142 clinicians (44%) who completed the study, most agreed that hematology and PC should work together and that both need to understand their roles. However, only about half of the patients were accessible to a PC team, and few professionals had received specialized training in this area. Most clinicians agreed that a referral should be made if the patient’s prognosis is less than three months or if symptoms are severe and persistent. They also decided that RBC transfusions might be needed even in advanced stages. All participants stressed the importance of having a dedicated case manager or team for effective referrals and organized training. More broadly, hematology experts generally support the inclusion of patients in PC care treatment plans. In addition, patients with HM avoid hospice care because of a lack of availability of RBC transfusions (95). Despite this, no prior research has been conducted on RBC transfusion administration from the perspective of hospice providers. A survey of 113 hospice providers revealed that only 2.7% of them routinely administer transfusions, 40.7% occasionally, and 54.9% never administer them. Non-profit organizations were found to provide more RBC transfusions than for-profit organizations. Additionally, 76.6% of the participants considered limited access a significant hindrance to patients with HM using hospice services, recommending an increase in reimbursement for transfusions (72.1%) to enhance enrollment. Therefore, palliative RBC transfusion is an essential barrier to the use of hospice. The study’s findings provide insight into the value of creative payment mechanisms in hospice care, aiming to improve EOL care for home hospice patients (96). In summary, overcoming administrative barriers and sustainably managing the associated costs, as well as selecting patients for transfusion properly and promoting alternative settings, such as home care, can facilitate the appropriate role of RBC transfusion in hematological PC.

Considerations for the very elderly

Centrally, differences in PC use in EOL among older patients indicate the need to expand the training and quantity of caregiving professionals, who represent a potentially restrictive factor in the effective control of symptoms and care, as well as determinants in this patient group. The sophistication of such an intervention reminds us of the imperative of flexibility of treatment protocols, considering the individual context of each patient. Evaluation of comorbidities, such as psychiatric illness, depression, anxiety, unresolved symptoms, and the burden on caregivers. The assessment of comorbidities, including mental health issues such as depression and anxiety, uncontrolled symptoms, and caregiver burden is an essential aspect (5). Older people, who are already at higher risk for muscle mass loss (75,78), frailty, and reduced exercise tolerance, may experience more severe effects from the non-hematological manifestations of AML. In addition, older people are more susceptible to medication side effects, especially in cases of polypharmacy (29,57,104). Furthermore, therapies aimed at symptom control may not sufficiently alleviate the significant symptom burden, particularly pain and dyspnea, as the illness progresses. They face risks of functional disability, osteoporosis, falls, and fractures, especially among those who rely on steroids. The physical and cognitive changes that are common in older individuals, particularly those aged 75 years and older, can hinder the proper administration of oral therapies, leading to insufficient dosing, which jeopardizes health outcomes, and diminishes QoL. Therefore, very elderly patients aren’t typically given intensive induction therapy. Recently, however, with the introduction of newer therapies, the disease outlook of this patient population has changed (5,40). Indeed, combination therapies, such as VENAZA, are typically applied to AML patients aged over 80 years and also in nonagenarians (36,37,105), including cases of very difficult-to-treat AML (106). Therefore, also AML patients with the most advanced age can now achieve a period of disease control using lower-intensity AML treatments. Hence, in light of the new therapies available, including oral decitabine (40) for unfit patients on VENAZA, no therapeutic nihilism can be justified. In this regard, all older patients should be carefully evaluated for the most precise personalization possible, based on their physical, psychological, and family and social well-being, reserving BSC exclusively for those who are too severely compromised, regardless of chronological age (27,107,108). The latter can serve as an initial evaluation guide, but it should not have absolute value in itself.

Ongoing studies and concerning issues

Contemporary research focuses on advancing PC integration in hematology and AML management (Table 5). In this regard, initiatives promoting this integration and discussing multidisciplinary strategies involving hematologists, PC specialists, and social workers (3) have been advocated. This holistic model emphasizes shared responsibility for managing complex symptoms alongside curative treatments or disease modification and addresses the need to incorporate PC principles into routine hematological practices to effectively address the multifaceted needs of patients with AML (2,60). In addition, AML management will also continue to evolve, necessitating a corresponding model for PC that aligns with changing treatments (10). Future studies will need to investigate various models for the delivery of PC, including inpatient and outpatient settings, to assess patient and caregiver understanding regarding PC and continue optimizing best practices for further implementation.

In summary, reported and emerging evidence demonstrates support for integrating EPC into AML management and, more broadly, in hematological practice as an essential model of care for alleviating symptoms and enhancing the QoL for affected patients. However, despite the known benefits, hospice and PC services remain underutilized in hematological contexts, and patients are often referred too late. Various reasons for these observations stem from the perceptions of hematologists and patients regarding PC, as well as other barriers, such as the use of blood transfusions in EOL care. Accurately identifying EOL stages for patients with hematologic cancers, including AML, is difficult due to the ongoing possibility of cures in advanced disease and the frequently rapid decline as death approaches. These concerns may lead to ineffective, if not harmful, therapeutic aggressiveness (9,60). This issue has been reported to delay the initiation of EOL care. Barriers to high-quality EOL care have also been identified as multifactorial, encompassing unrealistic expectations from both physicians and patients, the challenges of long-term patient-physician relationships that hinder EOL discussions, and the inadequacy of available home-based EOL care (7,91). Ongoing studies can be essential for refining integration methodologies and understanding their implications for patient care.

Conclusions

During the last decade, PC has been used to refer to a medical specialty that involves all aspects of medical care (4,61,109). PC has also been described as a patient-centered, dynamic, and holistically integrated model of care for family members and caregivers of patients of any age with life-threatening illnesses. It aims to enhance their QoL by evading, measuring, and reducing physical, emotional, social, and spiritual suffering. Hospice care is an integral aspect of PC, providing multidimensional care to patients near the end of their lives and their families. The aim is to allow patients to have dignity and peaceful death through the elimination of physical, emotional, social, and spiritual distress without the intention to abbreviate or prolong life, enhancing the QoL of caregivers and families (4,61,109). Once more, the importance of increased public awareness of hospice care has been highlighted, revealing it to provide emotional, social, practical, spiritual, and bereavement care to patients and their family members with life-limiting illnesses and EOL treatment. For this purpose, the hospice intends to enhance the QoL and dignity of individuals with life-limiting illnesses as well as their loved ones, family, and friends bereaved (110). These definitions have led to the current high-profile addition of EPC to AML management, with a focus on the value of care management for patients’ physical and psychosocial issues. EPC notably enhances QoL, symptom burden, and patient satisfaction among advanced cancer patients. In contrast to late PC, which focuses on acute interventions and heavy medication and symptom control, EPC can act at a longer interval and incorporate interventions with a focus on improved palliative, physical, and psychosocial well-being (63,110). Therefore, medical institutions are encouraged to integrate PC education into their curricula, equipping future professionals with the knowledge and skills to advocate for EPC in AML and, more broadly, in the context of malignant hematology.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://apm.amegroups.com/article/view/10.21037/apm-25-32/rc

Peer Review File: Available at https://apm.amegroups.com/article/view/10.21037/apm-25-32/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://apm.amegroups.com/article/view/10.21037/apm-25-32/coif). The authors have no conflicts of interest to declare.

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