What Is the Role for Palliative Care in Patients With Advanced Hematologic Malignancies?

Introduction and Scope of the Problem

Approximately 178,000 people are diagnosed with hematologic malignancies every year in the United States. These patients face highly unpredictable illness trajectories and intense treatment plans, resulting in complex psychological and physical symptoms. The high symptom burden of this population spans the entire disease continuum from diagnosis to the end of life and leads to poor quality of life. Accordingly, patients with hematological malignancies stand to benefit from palliative care. Timely integration of palliative care results in significant alleviation of physical symptoms and a decrease in anxiety and depression symptoms, and helps patients cope adaptively with their disease. Importantly, palliative care improves the quality of life of patients with hematological cancers.

Despite the palliative care needs of patients with hematological malignancies and the benefits of palliative care, rates of timely integration of palliative care are low. Indeed, patients with hematological cancers have the lowest rates of palliative care use in oncology. Hematologic oncologists are less likely than solid tumor oncologists to refer patients for palliative care, with referral rates ranging from 16% to 33%. In cases where referrals are made, they are often made close to the end of life, with the median time between first consultation and death reported to be as low as 12 days. Patients with hematological malignancies are also more likely to experience intensive health care utilization in the last month of life and are more likely to die in the hospital compared to those with solid tumors. Multiple studies have shown that having a hematological malignancy is a strong predictor of patients either never using hospice or enrolling very late in the disease course.

This chapter presents information about unique hematology-related factors that influence palliative care integration for this population. It also presents practical ways to promote timely integration. Finally, the chapter highlights future directions for effectively addressing the palliative and end-of-life care needs of patients with hematological malignancies.

Relevant Pathophysiology

Hematological malignancies are a heterogeneous group of cancers, comprising more than 60 distinct disease types, with varied clinical features, treatment pathways, and outcomes. Unique disease-related factors (e.g., low blood counts, heterogeneous disease states with respect to curability and survival) may increase symptom burden and unpredictability of the disease course. Moreover, treatments available for hematological malignancies may further compound symptoms and carry significant risk of morbidity and mortality. The growth of novel therapies, while promising, has also resulted in the unintended consequence of increased prognostic uncertainty and decreased predictability of the disease trajectory. The combination of these disease factors and various treatment plans ultimately influences integration of palliative care for this patient population.

Patients with hematological malignancies experience low blood counts (leukopenia, anemia, and thrombocytopenia) more often as compared to patients with solid malignancies. These differences result in an increased propensity in experiencing life-threatening infections, fatigue, bleeding complications, and a frequent need for blood transfusions. Higher rates of anemia may account for the fact that several studies note that fatigue or tiredness is the most prevalent physical symptom for patients with hematological malignancies. Patients with hematological malignancies also suffer from other symptoms including pain, depression, anxiety, constipation, and insomnia. Although the overall symptom burden of patients with hematological malignancies is largely comparable to those with advanced solid tumors, existing data suggest that rates and severity of symptoms such as fatigue, delirium, and drowsiness are higher. This difference in symptom profile requires additional attention when integrating palliative care to ensure that unique needs are adequately addressed. In addition, the higher propensity to suffer from anemia may negatively influence the rates or timing of hospice use if transfusions are not readily accessible in hospice settings.

The heterogeneous nature of hematological malignancies also influences integration of palliative care. There are several hematological malignancies that are potentially curable even in advanced or relapsed/refractory states, unlike advanced solid malignancies. This results in an unclear distinction between the end of curative therapy and the start of end-of-life care. Therefore if clinicians harbor the misperception that palliative care is only instituted when curative therapies are exhausted, this population will invariably have palliative care engagement too late in the disease course. The unclear definition of the end-of-life phase for this population may also lead to late hospice referrals. On the other hand, certain hematological cancers are incurable (e.g., chronic lymphocytic leukemia, follicular lymphoma), but have an indolent course and may have a lower symptom burden and prolonged survival. In addition, these diseases may respond well to multiple lines of treatment. These differences in symptom burden, disease course, and potential curability of various hematological malignancy subtypes make it challenging to identify the optimal timing and intensity of palliative care required as well as the appropriate time to transition to hospice care.

Patients with hematological malignancies also experience high unpredictability of their disease course and rapid changes in clinical status secondary to both their disease and treatments. For example, intensive treatments (e.g., hematopoietic stem cell transplantation, chimeric antigen receptor T-cell therapy), which may be potentially curative, may also result in severe complications with rapid deterioration that may contribute to lack of timely referral to palliative care or hospice services. The unpredictable disease course promotes uncertainty and may compound psychological symptoms of anxiety and depression. Accordingly, psychological support and adaptive coping skills are especially important components of palliative care for this population.