GVHD Biomarkers: Are They Ready for Prime Time?

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

Although the management of graft-versus-host disease (GVHD) is improving, it remains one of the major complications of allogeneic stem cell transplantation (SCT). Therefore, nurses must be aware of the ongoing efforts to better manage GVHD. One such effort is the use of sensitive, specific, timely biomarkers. Currently, biomarkers have significant limitations for clinical use, but the hope is that they will be readily available soon.


What Are GVHD Biomarkers?

Biomarkers are measurable substances in the blood, body fluids, or tissue that are signs of an abnormal process, condition, or disease, such as GVHD. Examples of biomarkers include:

  • Cytokines
  • T-cell surface markers
  • Proteins

A biomarker can often detect GVHD before the patient develops symptoms and help measure the patient’s response to treatment, such as steroid refractory GVHD.

What Are the Different Roles of GVHD Biomarkers?

GVHD biomarkers fall into 3 main categories to help determine risk, diagnosis, or prognosis.

  1. Predictive. Risk or predictive biomarkers can help assess the patient’s risk of developing GVHD. The goal is for a provider to use the biomarker results to determine the best prophylactic regimen for a more individualized approach. For example, patients at high risk for developing GVHD may decide to receive more intensive treatment. A predictive biomarker is typically done during the pre-transplant workup and again approximately 1 week after the transplant.


  1. Diagnostic. Biomarkers may help confirm a GVHD diagnosis. For example, if a patient develops significant diarrhea approximately 2 weeks after transplant, the provider may not attribute it to GVHD. A biomarker could confirm the gut GVHD diagnosis or that it is not GVHD but instead an infection.


  1. Prognostic. Biomarkers can identify the likelihood of the progression of clinical symptoms or GVHD and can help providers make better treatment decisions. In addition, prognostic biomarkers may give guidance for predicting outcomes at the onset of GVHD. For example, they can help determine overall survival or risk of death better than the patient’s clinical response to treatment.

What Is the Status of GVHD Biomarkers?

Several biomarkers are in clinical trials for acute and chronic GVHD in pediatric and adult patients. Two commercially available biomarkers, ST2 and REG3α, are used to determine the probability of developing acute GVHD before symptoms occur. Because initial research began with the Mount Sinai Acute GVHD International Consortium (MAGIC)—a group of more than 15 SCT centers collaborating to provide consistency in managing acute GVHD—they may be called the MAGIC biomarkers. Since ST2 and REG3α are primarily gut GVHD biomarkers, they may help predict patients’ risk for severe gut GVHD using the combined scores in an algorithm.

Although there is much interest in plasma biomarkers, currently, most healthcare providers agree that they are not quite ready for “prime time.” No GVHD biomarkers have completed the full approval process with the FDA. Their use is mainly in academic or research settings with interest from SCT providers for widespread clinical use. The challenge to applying these to real-world situations is the turnaround time of biomarker results. For example, a patient with a GVHD flare often needs immediate treatment and waiting a week or even 3 days for biomarker results may not be feasible. Therefore, the most promise is with risk biomarkers for acute GVHD or predictive biomarkers for chronic GVHD.

Nurses caring for SCT patients at risk for or with GVHD know the significant impact a simple blood sample result would have in preventing and managing GVHD. Since many nurses focus on side effects and toxicities, they know GVHD biomarkers could significantly avoid complications of GVHD and improve patient quality of life.

View Related Research at the Cancer Nursing Today GVHD Knowledge Hub