New Treatment for Reducing the Risk of Graft Versus Host Disease After Allogeneic Stem Cell Transplant

Can medications lower the risk of GvHD in stem cell transplant?

Patients undergoing an allogeneic stem cell transplant face the ongoing challenge of preventing graft-versus-host disease (GvHD), a potentially serious complication. This article explains a study of 159 adults who received a combination of tacrolimus, sirolimus, and mycophenolate mofetil to prevent GvHD after a reduced intensity conditioning transplant. 

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How Can GvHD be Prevented?

The study focused on a group of 159 patients at high risk of developing GvHD. Before the stem cell transplant, they received a reduced intensity conditioning chemotherapy and were given three medications to prevent GvHD: 

• Tacrolimus and sirolimus suppress the immune system, which weakens the negative effects of immune cells responding against donor stem cells.
• Mycophenolate mofetil is also an immunosuppressant, which prevents the rejection of transplants.

This strategy was applied regardless of donor type; whether from a matched related donor, matched unrelated donor, or a mismatched unrelated donor.

Key Study Findings

The study showed encouraging outcomes in terms of both survival and GvHD rates.

At one year after transplant:

• Progression-free survival (PFS) was 60%. After 3 years, PFS  decreased to 49%. 
• Overall survival (OS) was 70.3%. After 3 years, it remained at 61%.
• Non-relapse mortality (NRM) was 8.6%. After 3 years, it rose slightly to 10.4%.
• GvHD-free relapse-free survival (GRFS) was 44%. After 3 years, it was 32%.

These outcomes suggest the three-medication strategy is effective at controlling GvHD without increasing the risk of death from causes unrelated to cancer relapse.

Chronic versus Acute GvHD Rate

Acute GvHD typically appears soon after transplant, while chronic GvHD can show up months later. Here’s what the study found:

• Mild-severe acute GvHD (grades 2-4) affected 30.8% of patients by day 180.
• Severe-acute GvHD (grades 3-4) occurred in 13.4% of patients.
• Chronic GvHD developed in 41% of patients by year three, with 26.6% experiencing moderate to severe forms.

According to the NIH, acute GvHD occurs in 70% of cases and the chances for chronic GvHD ranges from 6% to 80%. This new combination offers a significant reduction in both presentations. 

Watch the HealthTree University course on graft versus host disease by clicking the button below. 

Managing GvHD

Donor Type Makes a Difference

Patients with matched donors had better outcomes than those with mismatched unrelated donors.  If you have questions about how to select a stem cell transplant donor, please contact your blood cancer specialist. 

Side Effects and Infection Risks 

Aside from GvHD, researchers looked at other side effects:

• Graft failure was rare (only 4 out of 159 patients). According to the NIH, the risk of transplant failure ranges from 5-60%. With this new combination, more people could benefit from transplant while reducing the risk of GvHD.
• Mouth sores were the most common side effect (32% had severe cases).
• Hemorrhagic cystitis (bladder bleeding) and other infections were infrequent and generally treatable.

The combination was generally well tolerated and did not lead to excessive side effects. Notably, rates of viral infections were low, possibly due to sirolimus’s antiviral activity and reduced use of steroids from fewer GvHD flare-ups. 

Next Steps

This approach balanced effectiveness and safety. These study findings can help guide therapy discussions with care teams, especially around donor selection and managing expectations for post-transplant outcomes.

You can continue your learning with HealthTree’s Stem Cell Transplant Patient Guide, a compilation of tips and knowledge created from patients, for patients.

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Source: 

• GvHD prophylaxis with tacrolimus, sirolimus, and mycophenolate mofetil after reduced intensity conditioning hematopoietic stem cell allogeneic transplantation