Graft-Versus-Host Disease vs. Graft Rejection: CML Bone Marrow Transplant Case Study Answers

Case scenario

An adult patient with chronic myelogenous leukemia sits down with you to discuss his questions and concerns about his upcoming bone marrow transplant. He has already received some educational materials and participated in a family conference during which health team members described the procedure and potential complications. He has been told that he has a risk of graft rejection or graft versus host disease (GVHD), but he does not understand the distinction.

1. What are the similarities between graft versus host disease and graft rejection?
2. What are the pathophysiologic differences between graft versus host disease and graft rejection?
3. How would these differences be manifested clinically?
4. Studies have shown a protective effect of mild to moderate GVHD in cancer patients who have had a bone marrow transplant. Based on your understanding, can you explain these findings?

Original example for study purposes.

Explaining it to the patient first

A simple way to start is: “After the transplant you will have two immune systems meeting for the first time: what is left of yours and the new one from your donor. In graft rejection, your immune system treats the donor cells as foreign and destroys them, so the new marrow does not take. In graft-versus-host disease, the donor’s immune cells treat your body as foreign and attack your skin, gut or liver.” Teach-back (“Can you tell me in your own words which immune system attacks which?”) confirms understanding.

1. Similarities

• Both are immune reactions caused by genetic differences between donor and recipient, mainly human leukocyte antigen (HLA) mismatches and differences in minor histocompatibility antigens. Closer HLA matching lowers the risk of both.
• T lymphocytes drive both. T cells recognize foreign HLA-peptide complexes, become activated, release cytokines and kill target cells.
• Both are prevented with immunosuppression (for example, calcineurin inhibitors such as tacrolimus or cyclosporine with methotrexate, or post-transplant cyclophosphamide) and by careful donor selection.
• Both can be life-threatening and both increase infection risk, because the patient is immunosuppressed and the immune system is either failing or under heavy treatment.

2. Pathophysiologic differences

3. Clinical manifestations

Graft rejection shows up in the blood counts. Primary graft failure means the neutrophil count never recovers (no engraftment by about day 28). Secondary graft failure means counts recover and then fall. The patient has persistent pancytopenia: infections and neutropenic fever from low neutrophils, bleeding and petechiae from low platelets, and fatigue and transfusion dependence from anemia. Chimerism testing shows loss of donor cells. Treatment may require a second transplant.

Acute GVHD usually occurs within the first 100 days and appears in the three classic organs:

• Skin: maculopapular rash, often starting on the palms, soles and ears, which can spread and blister in severe cases.
• Gastrointestinal tract: large-volume watery or bloody diarrhea, abdominal cramping, nausea, vomiting and anorexia.
• Liver: rising bilirubin and jaundice, elevated liver enzymes.

Chronic GVHD develops later and resembles autoimmune disease: dry eyes and mouth, oral lichen-like lesions, skin thickening (sclerosis) and joint contractures, lung involvement (bronchiolitis obliterans), weight loss and immune deficiency. Treatment starts with corticosteroids, with second-line agents for steroid-refractory disease.

In short, rejection is a failure of the new marrow (low counts), while GVHD is an attack on the patient’s organs (rash, diarrhea, jaundice) while the new marrow works.

4. Why mild to moderate GVHD can be protective

The same donor T cells that attack normal tissues also recognize the patient’s leukemia cells as foreign. This graft-versus-leukemia (GVL) effect destroys leukemia cells that survived chemotherapy and radiation. Horowitz et al. (1990) analyzed more than 2,000 bone marrow transplant recipients and found that patients who developed GVHD had lower leukemia relapse rates, while recipients of T-cell-depleted marrow or identical-twin grafts, which cause little or no GVHD, had higher relapse rates. Chronic myelogenous leukemia showed a particularly strong GVL effect, which is why donor lymphocyte infusions can be used to treat CML relapse after transplant.

The benefit applies to mild to moderate GVHD because the immune reaction is strong enough to control leukemia but not severe enough to cause organ failure or require heavy immunosuppression that leads to fatal infections. Severe GVHD raises transplant-related mortality and cancels out the benefit. The clinical goal is therefore balance: enough immunosuppression to prevent severe GVHD while preserving the graft-versus-leukemia effect.

Nursing implications

• Monitor daily blood counts and report failure to engraft.
• Inspect the skin, record stool volume and frequency, and follow bilirubin and liver enzymes.
• Use neutropenic precautions and give prophylactic medications on time.
• Teach the patient to report rash, diarrhea, yellowing of the eyes or skin, fever and bleeding right away.

References

Horowitz, M. M., Gale, R. P., Sondel, P. M., Goldman, J. M., Kersey, J., Kolb, H. J., Rimm, A. A., Ringdén, O., Rozman, C., Speck, B., Truitt, R. L., Zwaan, F. E., & Bortin, M. M. (1990). Graft-versus-leukemia reactions after bone marrow transplantation. Blood, 75(3), 555–562. https://doi.org/10.1182/blood.V75.3.555.555

Zeiser, R., & Blazar, B. R. (2017a). Acute graft-versus-host disease—Biologic process, prevention, and therapy. New England Journal of Medicine, 377(22), 2167–2179. https://doi.org/10.1056/NEJMra1609337

Zeiser, R., & Blazar, B. R. (2017b). Pathophysiology of chronic graft-versus-host disease and therapeutic targets. New England Journal of Medicine, 377(26), 2565–2579. https://doi.org/10.1056/NEJMra1703472