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


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

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—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.

Understanding Graft Versus Host Disease

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 de novo 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.

Tailoring Therapy for GVHD

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.

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.

Additional Resources—Chronic GVHD

• American Society for Blood and Marrow Transplantation

• Blood & Marrow Transplant Information Network

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