Corticosteroids, such as prednisone, are often the first treatment used for acute or chronic graft-versus-host disease (GvHD). Unfortunately, in some patients, standard steroid treatment may not work; this is referred to as steroid-refractory or steroid-resistant GvHD. This can happen in both acute and chronic GvHD.

Healthcare professionals may consider patients with acute GvHD to be steroid-refractory if symptoms:

• have worsened in any organ within 3–5 days of starting prednisone at ≥2 mg/kg/day (or an equivalent corticosteroid);
• have not improved within 5–7 days of starting treatment;
• or have not fully resolved after more than 28 days of treatment.

Chronic GvHD is considered steroid-refractory if symptoms:

• worsen after treatment with prednisone at ≥1 mg/kg/day for 1–2 weeks;
• or do not improve after treatment with prednisone at ≥0.5 mg/kg/day, or 1 mg/kg every other day, for 1–2 months.

In patients who do respond to steroids, the dose may be gradually reduced or tapered off over time. When steroids are reduced or stopped, in some cases symptoms may 'flare up' or worsen. Healthcare professionals refer to this as steroid-dependent GvHD.

Acute GvHD is said to be steroid-dependent if:

• the dose of prednisone cannot be reduced under 2 mg/kg/day after at least 7 days of successful treatment without symptoms getting worse;
• or symptoms return or worsen during a gradual steroid tapering period.

Chronic GvHD is said to be steroid-dependent if:

• symptoms cannot be controlled while reducing the prednisone dose below 0.25 mg/kg/day, or 0.5 mg/kg every other day, after at least two attempts separated by at least 8 weeks.

Some patients may also experience side effects from treatment with steroids. Examples of the potential side effects include:

• Infections
• Temporary or permanent loss of blood supply to the bone
• High blood pressure
• Diabetes
• Myopathy (a disorder affecting the skeletal muscles)
• Osteoporosis (brittle or fragile bones)

If side effects from steroids become too severe or harmful to the patient for them to continue to receive this treatment, they may be steroid-intolerant.

For patients who have steroid-refractory GvHD, or who are steroid-intolerant, other treatment options are available, such as:

• Extracorporeal photopheresis
• Ruxolitinib
• Ibrutinib
• Belumosudil
• Axatilimab
• Enrollment in clinical trials

Read more about GvHD treatment options.

References

1. Graft-versus-host disease. Leukemia & Lymphoma Society. https://www.lls.org/treatment/types-treatment/stem-cell-transplantation/graft-versus-host-disease. Accessed Jan 3, 2025.
2. Schoemans HM, Lee SJ, Ferrara JL, et al. EBMT-NIH-CIBMTR Task Force position statement on standardized terminology & guidance for graft-versus-host disease assessment. Bone Marrow Transplant. 2018;53(11):1401-1415. DOI: 10.1038/s41409-018-0204-7.