Recognizing GVHD Risk Factors

By Elaine S. DeMeyer, RN, MSN, AOCN®, BMTCN® - Last Updated: September 7, 2022

Oncology nurses must know the various factors that put patients at risk of developing graft-versus-host disease (GVHD). Although its prevention and management have improved, GVHD still occurs in 30%-70% of adult transplant patients and 30%-45% of pediatric patients. With a better understanding of risk factors, nurses can identify high-risk patients and gain an understanding of risk reduction strategies.

HLA Disparity: Critical GVHD Risk Factor

Although there are several risk factors for developing GVHD, one of the most important is the degree of HLA matching between the patient and donor. HLA stands for human leukocyte antigen and is part of humans’ major histocompatibility complex. These tissue histocompatibility antigens are found on the cell surface of leukocytes or white blood cells. They help the immune system know the difference between self and non-self (or foreign substances).

When the patient and donor share the exact HLA, they are considered a “match.” A closer match between the donor’s and patient’s HLA markers can lower the risk for GVHD. Depending on the transplant program, a complete HLA match is a 10/10 or 12/12. However, even if patients are a full match, they can still develop GVHD due to donors’ multiple minor histocompatibility antigens.

Numerous GVHD Risk Factors

There are numerous GVHD risk factors beyond HLA matching. Some risk factors are specific to the donor, the patient, or both. Compounding risk factors cause complexity in determining GVHD risk and potential severity.

  • Sex Mismatch. A female donor to a male recipient increases the risk for severity of acute GVHD and incidence of chronic GVHD. This risk is because males have H-Y antigens (minor histocompatibility antigens) encoded on the Y-chromosome. These antigens contribute to the development of GVHD.
  • Donor Parity. The number of previous pregnancies in a female donor also increases the risk of GVHD. Therefore, when given a choice, transplant physicians often prefer male donors over female donors or females who have never been pregnant (nulliparous).
  • Age. An older (40 years of age or older) donor or recipient increases the likelihood of GVHD, particularly chronic GVHD. The older age risk applies to all donors and recipients, including fully matched sibling transplants.
  • TBI. Patients receiving a higher dose (>1200 cGy) of total body irradiation (TBI) are more likely to have severe GVHD. Higher TBI dose causes more damage to the gut that contributes to more severe GVHD. Conversely, reduced-intensity conditioning with a lower, single-dose TBI often lowers the GVHD risk. These lower-dose regimens cause less tissue damage, resulting in less GVHD.
  • PBSC Graft Source. Since T cells are the primary cells involved in GVHD, the number of T cells in the stem cell source influences GVHD risk and timing. Peripheral blood stem cells (PBSC) contain the most mature cells and, therefore, contain the most T cells. Conversely, umbilical cord blood contains the immature cells with the least number of T cells.

Umbilical Cord Blood < Bone Marrow < Peripheral Blood Stem Cells

  • Unmanipulated Graft. Manipulating the graft to remove the T cells lowers the risk of GVHD. Although laboratory T-cell depletion may seem like a logical solution to prevent GVHD, it may also decrease the graft-versus-tumor benefit. In addition, removing T cells increases the risk of viral infection after transplant. 
  • Adherence. If patients do not take their immunosuppressants on schedule, they can develop GVHD, have a flare, or relapse. This concept can be hard to understand for asymptomatic patients. Nurses must educate patients about the importance of tacrolimus or cyclosporin dose and timing and keeping serum monitoring laboratory appointments.
  • Sun Safety. The sun’s ultraviolet rays increase the risk of developing acute and chronic GVHD, even years after stem cell transplant. Patients may not realize that even a few minutes in the sun or rays through a window or windshield can be enough to trigger GVHD. Nurses can improve education about sun safety using the Slip, Slop, Slap, Seek, Slide approach.
  • Viral Serology. Pretransplant donor and patient workups of cytomegalovirus (CMV), human immunodeficiency virus (HIV), hepatitis B or C virus, human papillomavirus (HPV), and Epstein-Barr virus help to identify the patient’s GVHD risk. If all things are otherwise equal among donors, a CMV-positive donor would be preferred because that donor will carry antibodies that would help if the patient reactivates the virus.

Some risk factors are unchangeable (i.e., age, sex mismatch), but others, such as adherence and sun safety, are modifiable. Given a choice, transplant physicians weigh all the GVHD risk factors together in donor selection and GVHD prophylaxis. Oncology nurses have a critical role in educating patients about their role in minimizing GVHD risk through medication adherence and sun safety.

View Related Research at the Cancer Nursing Today GVHD Knowledge Hub