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The transfusion tether: Bridging the gap between end‐stage hematologic malignancies and optimal end‐of‐life care

Two patients with refractory acute myeloid leukemia (AML) were recently treated at our institution. Patient 1 was a fit 72-year-old gentleman who failed to remit after high-intensity induction chemotherapy. Despite a second induction, his leukemia persisted. Although his functional status remained excellent, he eventually developed platelet-directed antibodies and required outpatient transfusion of HLA-matched platelets several times per week. When his leukemia eventually progressed, he suffered a stroke, leaving him unable to care for himself at home. Reluctant to forego lifeprolonging transfusion support, he refused to be discharged from the hospital unless he could continue to receive a similar level of transfusion support as he had been receiving. He remained hospitalized for 36 days while awaiting identification of a facility that was willing to continue transfusions. Patient 2 was a 79-year-old gentleman whose leukemia had been controlled for more than a year on various low-intensity, outpatient-based regimens. Like Patient 1, he too developed progressive transfusion dependence, requiring either blood and/or platelets multiple times per week. He had a long history of cardiovascular disease, and severe anemia typically precipitated dyspnea and angina, both of which resolved with transfusion. Unfortunately, his performance status steadily declined, and at his final clinic visit he felt so poorly that he requested to be “euthanized.” He was transferred from clinic directly to an inpatient hospice unit, where he died less than 24 hours later. Patients 1 and 2 illustrate one of the unique challenges faced by the practitioners who care for patients with advanced hematologic malignancies—the “transfusion tether.” Unlike many costly “breakthrough” treatments for solid tumors—typically lauded for providing modest gains in progression-free survival—many patients with terminal hematologic malignancies can live equally long and can feel better with intensive transfusion support alone. While recent studies suggest a benefit in terms of both quality of life and even overall survival in patients with solid tumors who receive early integration of palliative care, palliative care and hospice utilization for patients with hematologic malignancies remains low [1,2]. This is, in part, because no such data are yet available specific to these patients. Nonetheless, it seems reasonable to extrapolate that improvements in symptom management and end-of-life transitions might translate into similar gains for patients with liquid tumors. Interestingly, however, the very benefits afforded by transfusion support can paradoxically prevent patients with end-stage hematologic malignancies from receiving the more comprehensive palliative support provided by hospice care. A recent meta-analysis demonstrated that patients with hematologic malignancies were significantly less likely to receive specialist palliative care or hospice services compared to patients with solid tumors (RR 0.46, 95% CI 0.42–0.50) [3]. In another retrospective cohort of nearly 350 patients referred to the palliative care program at M.D. Anderson Cancer Center, the median time from palliative care referral to death was 0.6 months for patients with hematologic malignancies versus 2 months for patients with solid tumors (P< 0.001) [4]. At Massachusetts General Hospital and the Dana-Farber Cancer Institute, end-of-life health care utilization was specifically studied in older patients with AML, with only 47 of 330 patients (14.2%) ever receiving a palliative care consultation, and a median time from palliative care consultation to death of 7 days [5]. In our practice, reluctance to discontinue transfusion support at the end of life—whether patient-driven, physician-driven, or both—is one of the principal barriers to optimizing end-of-life care for our patients. While not explicitly contraindicated in the eligibility criteria for Medicare’s hospice benefit, hospice organizations frequently opt to exclude patients who wish to receive ongoing transfusions. A survey of 591 hospices in the United States found that 40% of hospices refused to allow transfusion support for their patients [6]. It is likely that a much higher percentage of hospices would have excluded patients with end-stage hematologic malignancies, whose transfusion needs are typically much higher than for the average terminally ill patient. The “palliative” benefit of transfusion support to reduce dyspnea, fatigue, bleeding, and weakness is relatively well-documented [7]. But in addition to receiving symptomatic relief, it is clear that many patients who continue transfusions also derive benefit from the regular interactions with the medical assistants, nurses, and physicians with whom they have formed strong personal connections over the course of their treatment. When patients cease to be able to receive transfusions, this network of support is severed. The obvious and not inconsequential impact of intensive transfusion support for patients with terminal disease is the financial burden placed on the healthcare system. Medicare hospice benefits pay a fixed, per patient, per day benefit to hospice organizations, regardless of the services