Palliative care for patients with haematologic malignancies: challenges and opportunities

Introduction

The landscape traversed by those living with haematological malignancy has changed significantly over a short number of years. Novel treatments, including cellular therapies, offer a real and much needed hope, especially for those living with diseases with previously limited treatment options. The global haemato-oncology community has worked successfully to improve outcomes for many patients, but alongside this progress sits the reality that some patients’ disease will not respond and they will sadly die. These patients often spend the last weeks and months of their lives in hospital, away from their loved ones, enduring the therapies that aim to prolong their lives.

Over the past 15–20 years, robust evidence has demonstrated the value of introducing palliative care early in the cancer journey. No longer limited to end-of-life care, palliative care is now recognized as beneficial alongside active cancer treatment, particularly for patients with solid tumours. Patients experience improved quality of life, better symptom control, fewer crises, and enhanced understanding of prognosis, which supports coping and decision-making (1-3).

Evidence supporting palliative care for patients with haematologic malignancies

Increasing numbers of studies, including randomised controlled trials, demonstrate the role that palliative care plays in supporting patients with haematological malignancies to navigate the complexities of their diagnosis and treatments, empowering patients to sustain as good a quality of life as possible whatever the ultimate outcome (4-6). In 2024, the American Society of Clinical Oncology (ASCO) published updated guidance on palliative care for patients with cancer. This included a specific evidence-based recommendation that palliative care should be available to all patients with haematological malignancies, regardless of prognosis (7).

The aforementioned two studies upon which the ASCO recommendation was founded examined specialist palliative care input compared with standard care: (I) for in-patients with acute myeloid leukaemia (multi-centre study, n=160) (4); and (II) for patients with a variety of diagnoses undergoing haematopoietic stem cell transplantation (HSCT) (single centre study, n=160) (5). Both demonstrated evidence for benefit in terms of improved quality of life and reduced psychological needs [depression, anxiety, post-traumatic stress disorder (PTSD)]. The study in patients undergoing HSCT was subsequently extended to a multi-centre study (n=360) in the same patient population, with similar impact demonstrated on quality of life, depression, anxiety and PTSD at 2 weeks (8).

Challenges for delivering palliative care for patients with haematologic malignancies

Although a palliative approach to care can be delivered by any healthcare professional, whether or not they have additional training and experience in palliative care (often described as primary and secondary palliative care and provided in community, primary care, or hospital settings), integration between oncology and specialist (tertiary) palliative care for patients with haematological malignancies remains a key challenge. Effective integration is essential to ensure that palliative care delivery and service development across settings and specialties are supported by healthcare professionals with advanced expertise, enabling complex clinical decision-making and the provision of specialist advice, support, education, and training to the wider care team (9).

The ASCO guidelines present several challenges in the development of effective, integrated palliative and supportive care services for patients with haematological cancers. Central to this is not whether palliative care should be delivered, but how and when. This includes extending provision to patients including, but also beyond, those undergoing HSCT, ensuring that patients with a wider range of haematological diagnoses and undergoing a wide range of treatments can all benefit from the holistic approach of palliative care (10). Firstly, supportive and palliative care services are traditionally not well integrated with haem-oncology. Patients with haematological cancers are often referred late to palliative care, if at all. The end of life is often associated with hospitalisations and invasive interventions, including intensive care unit admissions (11). Prognostic uncertainty, the intensity of ongoing clinical interventions, reliance on blood products, and the presence of long-standing therapeutic relationships between patients and haematology-oncology teams have been identified as key barriers to early, proactive referral to palliative care (12,13).

Secondly, the heterogenous nature of haematological malignancies, specific and often intensive treatment strategies and supportive care needs (e.g., transfusion requirements) means that approaches to the integration of palliative care services must be tailored to the unique trajectories and needs of specific patient groups (14). Shaulov et al. propose distinct cohorts of haematology patients based on trajectory of disease according to functional status (15). Although these trajectories are not mutually exclusive and are complicated by the fact that patients may move between cohorts depending on their disease and available treatments, each trajectory is associated with distinct palliative care needs that vary according to the patient’s stage in their disease or treatment journey. This categorisation offers a pragmatic framework for guiding the development and delivery of palliative care services in haematology.

Haematological malignancies with a predominately “indolent trajectory” include chronic lymphocytic leukaemia, indolent lymphomas and many cases of myeloma (15). These treatable but often not curable diseases are associated with multiple relapses. Numerous lines of cancer treatments are available and response to treatment can be unpredictably favourable, resulting in challenges in terms of prognostication and ceiling of treatment decision-making. Patients with myeloma often present with physical and psychological needs that mirror those in solid tumours (16,17). The “indolent” functional trajectory is made up of periods of stability interspersed by periods of decline, often associated with repeated periods of hospitalisation. Models of early proactive palliative care for patients with myeloma have been shown to be both feasible and effective (18,19). Further research is needed to determine the optimal timing and stage at which palliative care involvement can provide the greatest benefit to the large volumes of patients in this cohort.

“Aggressive” life-threatening haematological malignancies have a high risk of mortality and morbidity, due to both the disease and the intensive treatment options (15). This group includes acute leukaemias, aggressive lymphomas, patients undergoing stem cell transplantation and those presenting with acute graft-vs.-host disease. Specifically, for patients with these diseases, there is often a realistic possibility of cure.

Palliative care for patients receiving newer haemato-oncological treatments

The disease trajectory of many haematological cancers has been revolutionised with the introduction of novel therapies such as T cell engagers which have simultaneously shown great promise whilst expanding the significant uncertainty for individual patients, in whom it is unclear if the therapy will bring about a long-term remission. The prognostic uncertainty that underlies so many blood cancers, is evermore stark as new therapies are embedded, many of which lack long term outcome data.

Chimeric antigen receptor T (CAR-T) cell therapy is an example of an innovative and potentially life-saving immunotherapy for patients with relapsed or refractory haematological malignancies who have not responded to previous lines of treatments. Approximately 50% of patients achieving long-term disease-free survival but outcomes are characterised by significant prognostic uncertainty (20,21). Patients undergoing CAR-T therapy (and the more recently developed bispecific antibody therapy) can also be included in the cohort of patients with high risk but potentially curative disease. Consideration of the needs and trajectory of patients undergoing CAR-T therapy can be used an example to illustrate some of specific considerations for integrating palliative care in patients with “aggressive” disease trajectories.

CAR-T follows a defined clinical course that can be understood longitudinally, encompassing the pre-CAR-T phase, the immediate post-infusion period, and longer-term follow-up (22). Implementation of effective and holistic palliative and supportive care services demands consideration of the specific and changing needs of patients and their families at each stage of the treatment course.

Patients being considered for CAR-T therapy or bispecific antibodies will have relapsed/refractory disease, and often present with challenging physical symptoms because of their disease and prior treatment/s (23,24). By the time patients are offered CAR-T therapy, they have may have endured a prolonged and challenging treatment journey, resulting in a substantial psychological burden shaped by the cumulative “rollercoaster” of their disease and prior therapies (24). CAR-T therapy itself is associated with a constellation of unique toxicities (cytokine release syndrome and immune effector cell associated neurotoxicity syndrome) that require active medical management, often in intensive care, alongside the challenge of navigating an uncertain, yet potentially curative, disease trajectory. This demands a high level of integration of palliative care with the haemato-oncology teams, as well as intensive care teams and supportive care teams to provide appropriate, effective and holistic care (25).

Although there are palliative care services that have embraced this innovative approach and have adapted to deliver care that is both routine and embedded, this is far from within the standard palliative care remit, and resource limitations as well as concerns about blurring of boundaries are likely barriers. An initial major barrier is that haematology teams may lack awareness or insight into the role that palliative care can play in supporting this complex symptomatology and may not consider referral to specialist teams in the context of a therapy being given with curative intent. A review of patients undergoing CAR-T cell therapy who died demonstrated significant hospital utilization in the last 30 days of life. Most patients were shown to have died in a hospital or healthcare facility. Unfortunately, most patients did not have input from palliative care services (26). Where there has been palliative care involvement, this is often late, occurring soon before death occurs, in keeping with recognised patterns in those with haematological malignancy compared with solid organ malignancies (15,27). While the immediate post-CAR-T infusion period is psychologically taxing, it is also associated with a considerable physical symptom burden, including fatigue, pain, sleep disturbance, anorexia, and profound weakness (28). Symptom management during this phase requires careful consideration of the treatment’s potentially curative intent and challenges palliative care teams to extend their scope of practice beyond the care traditionally focused on patients with advanced, incurable disease. A particular consideration is the use of opioids vs. non-opioid approaches for pain management.

Long-term outcomes following CAR-T therapy raise important questions about the role and scope of supportive and palliative care. Patients may experience significant psychosocial challenges, such as fear of cancer recurrence and PTSD, alongside physical issues, including fertility concerns (29). The optimal role of palliative care for this population remains to be clearly defined.

Longitudinal studies demonstrate the evolving and dynamic changes in multiple domains of quality of life in patients with haematological malignancies, relative to the course of their treatment. In one study of patients undergoing HSCT, these changes appeared to be parabolic, with a marked deterioration at day 6 post-transplant and gradual improvement at discharge (30). Longer-term follow-up highlights the significant psychological needs of HSCT patients 6 months after transplant with 28% and 43% meeting the criteria for PTSD and depression respectively in one series (31). A longitudinal study of patients receiving CAR-T therapy revealed that 28% of patients experienced severe physical symptoms at 6 months, and nearly a quarter of patients reporting clinically significant anxiety, depression or PTSD (32).

Considering the evolving and dynamic needs of patients throughout their treatment pathway, it is unsurprising that a short, 2-week inpatient palliative care intervention showed no sustained impact on most physical and psychological quality-of-life indicators for patients undergoing stem cell transplant (8). Although this limited duration was likely necessary due to resource and trial constraints, how to implement longitudinal, targeted, and timely support outside of a trial setting remains to be determined.

Opportunities for palliative and supportive care service development for patients with haematologic malignancies

There exist engrained and pervasive inequalities in the palliative and end-of-life experience of those with haematological malignancies. These diseases are often considered potentially curable, sometimes until soon before death and traditional models of palliative care have struggled to understand how to support holistic care in the context of this uncertainty.

Palliative care has developed a clear understanding of the need to give patients opportunities to think and plan for their own future, including time and space to talk about the ‘what ifs’ of treatment failure (33). The uncertain future faced by those living with haematological malignancy, exacerbated by the unclear outcomes of novel therapies, can complicate the initiation of timely advance care planning discussions (34). Literature describes the reality for patients of living with a ‘Double Awareness’ of simultaneous life and potential death (35). A framework of ‘Parallel Planning’ is proposed, in which patients are supported within this dual reality to consider their priorities and continue to hope for treatment success whilst simultaneously exploring the potential of treatment failure. This enables patients to be fully empowered and involved in planning for their future, ensuring that care is fully goal-concordant (36).

Models of supportive and palliative care, which historically have been dichotomous and limited to those in whom substantive treatment options are no longer available, must flex and offer timely, responsive, and adaptive care, identifying needs along the disease and treatment pathways and initiating appropriate interventions (7,37). Concerns as to resource exist and must be weighed as an important barrier to innovation. A specific challenge for palliative care in haematology is how to balance available resources whilst also being proactive and adaptive to needs. El-Jawahri et al. demonstrate the value of a model in which palliative care, rather than being dependent on specific referral criteria/triggers is instead routine and embedded within the stem cell transplantation process (8). This normalised proactive embedded model works well in haematology where prognostic outcomes are uncertain. Further evidence is needed regarding benefit and sustainability in this and other contexts and treatment modalities.

Testing efficient, holistic, outpatient-based strategies, based on proactive needs screening (38,39) or referral “triggers” (40) is the basis for “precision palliative care”, as a means of ensuring sustainable palliative care service delivery (41). This approach works to identify specific patients’ and caregiver needs that would warrant palliative care input at a given timepoint and may help services to identify those most likely to benefit. There is little published evidence identifying which haematology-specific triggers indicate when palliative care involvement may provide added value. As with solid tumour oncology, potential triggers may include needs-based criteria such as the severity or specificity of symptoms, as well as key periods of complex treatment decision-making, for example, when patients are being evaluated for high-intensity therapies such as CAR-T cell therapy or HSCT. Additional markers of changing health status may also be relevant, including recurrent unplanned hospital admissions, a decline in functional status or increasing dependence on blood products (42). Establishing and evaluating clinically meaningful referral triggers should be prioritised as a key next step in future research, with the recognition that in haematology, appropriate triggers for palliative care involvement may need to be tailored according to diagnosis and/or treatment options (14).

Patient reported outcome (PRO) measures, increasingly an established feature of palliative care research, may play a role in empowering patients to proactively highlight emergent issues that could benefit from specialist input (43). Longitudinal use of PROs, especially with the implementation of digital PROs, throughout the disease trajectory has the potential to: (I) proactively identify evolving patient needs (32); (II) enhance communication and collaboration between patients and clinicians (44); and (III) support stratified access to early palliative care by prioritising patients with emerging or unmet needs (38,39,45). While PRO measures have been developed or evaluated within specific haematology cohorts, such as myeloma (46,47), HSCT (30) and CAR-T populations (32), a recent systematic review highlighted the complexity of PRO implementation, requiring coordinated planning and organisational support (48). To date, the routine, normalised use of PROs for patients with haematological malignancies has not been widely documented. Further research is needed to identify the most effective and sustainable ways for palliative care and haematology teams to work together. Strengthening integrated collaborative working practices could enhance shared understanding and support reciprocal, patient-centred learning, areas that have been recognised as inconsistently achieved in current practice.

Advancing palliative care for patients with haematologic malignancies: a call to action

As in solid tumours, a challenge facing healthcare providers now is how best to integrate palliative care to provide holistic, integrated, coordinated care across pathways and service settings. In haemato-oncology, this requires addressing unique barriers, such as unpredictable disease courses, difficulties with prognostication, the implications of multiple and complex treatment options and overarchingly, the potential for curative intent. The time is right to embrace these challenges. Pragmatic strategies should include developing new palliative care models that are embedded and normalised within haemato-oncology, where parallel planning and targeted, trigger-based referrals supported by longitudinal PROs underpin patient-centred and patient-directed care. Rigorous research will be essential to guide and sustain their implementation.

It is imperative that such approaches are routinely commissioned and embedded into all haemato-oncology pathways in order to address unacceptable inequalities which serve to deny patients much needed multi-disciplinary care.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Annals of Palliative Medicine. The article has undergone external peer review.

Peer Review File: Available at https://apm.amegroups.com/article/view/10.21037/apm-2026-1-0014/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://apm.amegroups.com/article/view/10.21037/apm-2026-1-0014/coif). Both authors report that they are undertaking a research project funded by Kite Gilead. The funders had no role in the development, delivery or the study, analysis or dissemination of results. J.V. has done work for several pharmaceutical companies including involvement in sponsored educational packages. She is a member of the UKASCC board and the conference chair. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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