As clinical providers, the ability to meet the science of medicine with its physical, emotional, spiritual, and financial impact it has on patients is often unintentionally overlooked or, at the very least, minimized during the active treatment phase of care; therefore, the purpose and potential benefits that result from integrating palliative care early on in the process is missed.

 led by Areej El-Jawahri, MD, of Massachusetts General Hospital Cancer Center in Boston, 160 patients with hematologic malignancies admitted for autologous or allogeneic HCT noted improvement in quality of life as evidenced by increased understanding of illness, lower rates of depression, anxiety, and symptom burden during hospitalization as a result of receiving palliative care services.

Logically, the next question becomes why haven’t we been more proactive in setting into motion these services, which seemingly only benefit this patient population? In my opinion, it is the historical stigma that surrounds “palliative care” that detracts both providers from implementing it early on in the care plan as well as patients from embracing the resources inherently connected to it.

Palliative care is wrongly thought of as only “end of life” care and consequently often implemented as such. As the ability to transplant older patients with higher risk comorbidities continues to grow, we need to acknowledge that the net result is a patient population with greater needs both emotionally and financially. What happens to the 70-year-old man who has limited financial means because he is not actively working, and then is forced to cope with chronic graft-vs-host disease—an all-too-common and potentially debilitating complication associated with allogeneic stem cell transplantation? It is this scenario, as well as a multitude of others, that must empower providers to truly understand what palliative care is, what it does, who it can benefit, and how to convey it to their patients in an appropriate and timely fashion so that the patient is willing to accept the services that palliative care can provide for them.

This discussion would be remiss if we did not acknowledge, however, that the “end of life” aspect of palliative care does exist, and it, too, is often not discussed until a patient is actively passing or in the immediate days prior to his or her death. Thus, neither the patient nor the patient’s family members truly benefit from the variety of services available to them. Once again, it is the responsibility of the provider and healthcare team to become knowledgeable and comfortable speaking about what is truly important—the quality of life of the patient and how best to optimize it.

The emotional and physical “roller coaster ride” that each of our patients embarks on as they undergo hematopoietic stem cell transplants should automatically guarantee them a holistic care approach of medicine that includes the input and expertise of physicians, nurses, mental health experts, social workers, allied health professionals, and ancillary services—all working in partnership as a palliative care team. It is there that the “missing link” in the care provided for these patients is found.

Mary E. DiLorenzo, MSN, RN-C, NP-C, is an advanced practice nurse in the Blood and Marrow Transplantation Program at John Theurer Cancer Center in Hackensack, New Jersey.

Articles

The "Missing Link" in Hematopoietic Stem Cell Transplantation

Our immune system’s successful detection and destruction of abnormal cells is the hallmark of our body’s ability to either stop a malignancy from occurring or halt it once it has begun. However, cancer cells are sometimes able to evade one’s natural defense mechanism, thus allowing proliferation and manifestation of a particular disease to occur. Therefore, it comes as no surprise that cancer therapies are increasingly more focused on immunotherapy and the use of targeted agents to directly “unleash” a patient’s immune system in an attempt to slow down or terminate production of cancer cells in the host.

One immunotherapy approach is to block the ability of certain proteins, called immune checkpoint inhibitors, to limit the strength and duration of the immune reactions. These proteins normally keep immune responses in check by preventing overly intense reactions that might damage or destroy normal cells as well as abnormal cells. However, research has proven that certain tumor cells can take control of these proteins and use them to suppress the body’s natural immune responses.

Blocking the activity of immune checkpoint proteins releases the “brake” on the immune system, increasing its efficacy to destroy malignant cells. One such agent that has been recently FDA-approved in the treatment of classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin is 

Nivolumab is a human monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Binding of these ligands to the PD-1 receptor found on T cells, inhibits T cell proliferation and cytokine production. Nivolumab binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, thus preventing the inhibition or “brake” on the immune response, resulting in an antitumor immune response and decreased tumor burden.

Thus, one may be tempted to say that this is the perfect solution to an imperfect scenario; however, when discussed within the context of allogeneic stem cell transplantation, red flags regarding potentially life-threatening complications must be addressed.

Although allogeneic HSCT has revolutionized the manner in which providers view the interplay between hematologic malignancies and their appropriate therapeutic treatment options, one would be remiss to ignore the fact that an all-too-common complication of donor HSCTs, known as graft versus host disease (GVHD), potentially limits the use of certain immune-modulating agents, or at the very least, heightens awareness of their side effect profile.

The pathophysiology behind GVHD can be compared to an overactive or “brake-less” immune response, in which donor-derived T-cells attack the host and produce a multitude of sequelae, ranging from those which are relatively responsive to initial corticosteroid therapy, to ones that are refractory and the driver of possibly life-threatening complications.

Therefore, the decision to use checkpoint inhibitors in the context of allogeneic HSCT must be done while taking into consideration the possible interplay between the known mechanism of action of the drug as well as the potential complication known as GVHD—a net result being a host’s immune system that is “unhinged” and indiscriminately attacks both nonmalignant and malignant cells.

Providers must choose patients wisely, analyzing a patient’s comorbid conditions eg, Crohn’s disease, ulcerative colitis, lupus, pulmonary/liver disease, and drug profile history (specifically any drug that weakens the immune system) eg, antithymocyte globulin, corticosteroids, and calcineurin inhibitors, that would predispose them to developing more severe complications.

Nurses must be diligent in systematically monitoring for adverse events including, but not limited to: hyperacute GVHD, severe acute GVHD, hepatic veno-occlusive disease, pneumonitis, colitis, hepatitis, adrenal insufficiency, encephalitis, as well as other immune-mediated adverse reactions.

As advances in immunotherapy and allogeneic HSCT occur, it is the ethical responsibility of every healthcare provider to educate him or herself on the latest FDA drugs available to treat such aggressive malignant conditions, while at the same time remember that once a host’s natural immune system has been given the “green light,” a necessary and effective “red light” must be ready and available for use in the provider’s arsenal. It is then that patients will have been given the most effective and safe therapy to treat their specific disease.

Our immune system’s successful detection and destruction of abnormal cells is the hallmark of our body’s ability to either stop a malignancy from occurring or halt it once it has begun.

Immunotherapy and Allogeneic HSCT: Unleashing Your Patient's Immune System Safely

At a recent meeting hosted by the National Institutes of Health and the American Society for Blood and Marrow Transplantation, some of the most preeminent physicians and researchers shed light on the all-too-familiar and intricate topic of chronic graft versus host disease (cGVHD) in the allogeneic hematopoietic-cell transplant (HCT) patient population.

As I listened to these experts, I realized that our responsibility as nurses and midlevel providers is to first educate ourselves, and then—most importantly&mdash;our patients, about this potentially debilitating complication. Even more important, we must share the hope that the latest experimental treatment modalities have provided for the prevention and treatment of cGVHD.

First, how do we make sense of the inherent paradox that cGVHD is to each of our patients? As providers, we preach that the untoward manifestations seen in cGVHD may in fact simultaneously provide the added benefit of a GVL (graft vs leukemia/lymphoma/myeloma) effect which may play a role in durable remission rates.

This can be a hard sell to a patient sitting across from you on the examination table who for the last 6 months has been experiencing moderate oral pain secondary to treatment-refractory oral cGVHD and progressive sclerotic-like skin changes that now prevent her from doing simple everyday activities, such as climbing stairs or raising her arms above her head.

In order to be successful, we must understand the pathophysiology of cGVHD. GVHD is an immune-mediated disease resulting from an intricate interaction between donor and recipient adaptive immunity. Acute GVHD describes a distinctive syndrome involving the skin, liver, and GI tract developing within 100 days after allogeneic hematopoietic-cell transplantation (HCT). Chronic GVHD describes a more diverse syndrome developing after day 100, manifesting in the skin, ocular, oral, pulmonary, GI, and/or GU systems.

Chronic GVHD may be an extension of acute GVHD; it may manifest 

 in patients who never have clinical evidence of acute GVHD, or emerge after a quiescent interval after acute GVHD resolves. Chronic GVHD is observed in 33% of human leukocyte antigen (HLA)—identical sibling transplantations, 49% of HLA-identical related transplantations, and 64% of matched unrelated donor transplantations. The rate could be as high as 80% in 1-antigen HLA–nonidentical unrelated transplantations.

The source of donor graft affects the incidence of GVHD. The cumulative incidence of cGVHD (and extensive GVHD) is higher in those who received peripheral blood stem cell (PBSC) transplant (73% vs. 55%). Cumulative incidence of Grades III-IV acute and extensive cGVHD is higher in unrelated cord blood recipients than in either recipients of HLA-identical sibling bone marrow or PBSC transplants.

Although not fully understood, cGVHD is often driven by an antigen mismatch; however, having a match-related HCT is not a guarantee that cGVHD will not develop. Hypotheses suggest that it is the upregulation of donor-derived activated T cells in target organ sites (eg, eyes, mouth, skin, lung, genitourinary tract), and subsequent downregulation of T regulatory cells that drive this process at the cellular level. Therefore, it makes sense that current research protocols are focused on methods that either inhibit this process from starting, halt it when it begins, or reverse the damage to some extent after it has occurred.

For example, posttransplant cyclophosphamide in haploid-identical transplants, palifermin in unrelated donor HCTs, and imatinib use in patients with sclerotic-like skin changes, are just a few of the latest approaches being studied and tested.

More often than not, the idea of choosing the “perfect drug” to treat cGVHD is nearly always met with the necessity of adding a second- or even third-line agent to help ameliorate the sequela of cGVHD. Patients with cGVHD of the lungs, now commonly referred to as “BOS” (bronchiolitis obliterans syndrome), have for years passively watched their lung function and subsequent quality of life progressively decline with only meager hope provided by clinicians.

The trifecta treatment approach known as FAM (fluticasone, azithromycin, and montelukast) can potentially improve a patient’s lung function, as evidenced by an increase in forced expiratory volume percentages, a decrease in supplemental oxygen requirements, and subjective patient reports. FAM also minimizes the patient’s exposure to systemic corticosteroids, thus decreasing treatment-related morbidity secondary to prolonged steroid use.

How does a provider choose the appropriate drug or drugs for that patient whose cGVHD manifestations have now negatively impacted his or her quality of life? We have to take into account the mechanism of action driving the cellular changes as evidenced by cGVHD, the individual patient safety profile, as well as the feasibility and/or availability of the treatment choice in question.

Yet, in a data- and research-driven area, perhaps just as important to the overall health and survival of these patients, is our attention to their mental health and the inevitable psychosocial impact cGVHD has on their personal and professional relationships.

As healthcare providers, we are in a unique position to serve as our patients’ advocate and educator by providing them with facts, options, encouragement, and a forum in which their questions or concerns can be answered based on research, as well as our own clinical expertise.

We are often the individual who makes the human connection with patients, and it is in that established relationship where most of them find solace and the ability to effectively cope. In the words of one of my patients, “First, comes outrage and denial. Then surrender. Then a steely resolve to fight like hell.”

As providers, we must fight to turn the stigma of cGVHD into a “friend,” or at the very least, not an enemy.

• American Society for Blood and Marrow Transplantation 

• Blood & Marrow Transplant Information Network 

http://www.bmtinfonet.org/after/chronicgvhd

At a recent meeting, some of the most preeminent physicians and researchers shed light on the all-too-familiar and intricate topic of chronic graft versus host disease (cGVHD) in the allogeneic hematopoietic-cell transplant (HCT) patient population. 


Mary E. DiLorenzo, MSN, RN-C, NP-C

Articles

The "Missing Link" in Hematopoietic Stem Cell Transplantation

Immunotherapy and Allogeneic HSCT: Unleashing Your Patient's Immune System Safely

Chronic Graft Versus Host Disease ... Friend or Foe?