Consensus reached on initial treatment of acute graft-versus-host disease in patients who receive bone marrow transplant; nothing definitive yet for secondary treatment

Oct. 09, 2020

Jeanne M. Palmer, M.D., a hematologist and oncologist in the Bone Marrow Transplant Program and Hematology at Mayo Clinic's campus in Phoenix/Scottsdale, Arizona, discusses treatments for bone marrow transplant patients with acute graft-versus-host disease.

A bone marrow transplant, also known as an allogeneic stem cell transplant, is a procedure that infuses healthy, blood-forming stem cells into a patient to replace damaged or diseased bone marrow. Bone marrow transplants can be lifesaving for patients. However, there are numerous risks, ranging from mild to life-threatening.

One of the major complications of allogeneic stem cell transplant is graft-versus-host disease (GVHD). GVHD occurs when the donor immune cells start to attack the healthy tissues of the recipient. GVHD is further divided into acute versus chronic GVHD, based on the symptoms and clinical features.

Acute GVHD

Acute GVHD typically occurs during the first months after the stem cell transplant. It affects the skin, digestive tract or liver and can manifest as a rash, elevated liver enzymes, or gastrointestinal signs and symptoms such as nausea, vomiting or diarrhea.

First line treatment

First line treatment of acute GVHD typically consists of steroids: either intravenous methylprednisolone or prednisone taken orally. Patients generally receive a steroid dose of 0.50 to 2 mg/kg. If the patient is responding, the dose is gradually tapered off over time. If the patient isn't responding after three to five days, the patient is defined as steroid refractory, and second line treatments must be considered.

Second line treatment

Cases of steroid-refractory acute GVHD are much more challenging to treat. Historically, there have been multiple therapies that demonstrated efficacy in the second line setting. However, none of those treatments has shown efficacy in a multicenter, randomized clinical trial.

In 2019, however, ruxolitinib, a Janus kinase1/2 inhibitor, was approved for treatment of acute GVHD. In 2020, a randomized study published in NEJM comparing ruxolitinib to best available therapy showed a clear advantage to use of ruxolitinib, both in overall response and in durability of the response. Ruxolitinib is currently FDA approved for second line treatment of acute GVHD.

Chronic GVHD

Chronic GVHD is a form of GVHD that can occur at any time following transplant, although it usually occurs after three months. Certain diagnostic criteria, created by the National Institutes of Health in 2004 and updated in 2014, must be met for GVHD to be considered chronic GVHD. Updated criteria were published in Biology of Blood and Marrow Transplantation in 2015.

Almost any organ system can be affected by chronic GVHD, which commonly presents as dry mouth, dry eyes, skin tightness, joint tightness and even lung disease. Often, late-onset acute GVHD presents along with chronic GVHD and is characterized as overlap GVHD. The classic chronic GVHD signs often include an overlap of both active inflammation as well as scar tissue formation, making it challenging to treat.

The treatment for this form of GVHD is similar to that of acute GVHD, usually starting with steroids. However, as many manifestations of chronic GVHD are due to scar tissue formation, it is important to be careful to avoid too much immunosuppression, as some of these manifestations do not improve.

Second line therapy for chronic GVHD historically has been very difficult. As seen in acute GVHD, there are many single-center studies showing efficacy, but there has been a failure to demonstrate similar efficacy in a multicenter setting. In a study published in Blood in 2017, however, ibrutinib, an inhibitor of Bruton tyrosine kinase and interleukin 2 inducible T cell kinase, showed efficacy in treatment of chronic GVHD in a multicenter study. Ibrutinib is currently approved by the FDA as second line therapy for chronic GVHD.


GVHD remains a challenging complication of allogeneic stem cell transplantation. It is particularly difficult to treat when it persists despite steroid treatment. For the first time, there are now two approved second line therapies for treatment of steroid-refractory GVHD ― one for acute GVHD and one for chronic GVHD. Hopefully these two therapies will be the first of many to help patients with this devastating complication.

For more information

Zeiser R, et al. Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease. NEJM. 2020;382:1800.

Jagasia MH, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and Staging Working Group report. Biology of Blood and Bone Marrow Transplantation. 2015;21:389.

Miklos D, et al. Ibrutinib for chronic graft-versus-host disease after failure of prior therapy. Blood. 2017;130:2243.