Treatment of Graft-Versus-Host Disease (GVHD)

Graft-versus-host disease (GVHD) is the ultimate “frenemy” of bone marrow and stem cell
transplantation. On one hand, donor immune cells help clean up any leftover cancer cells
(the graft-versus-leukemia effect). On the other hand, those same cells can mistake the
patient’s organs for invaders and attack them. Treating GVHD is all about balance:
calming the immune system enough to protect the body while trying not to lose that
helpful anti-cancer effect.

In this guide, we’ll walk through how GVHD is prevented and treated today, including
first-line options like steroids, newer targeted therapies such as ruxolitinib,
ibrutinib, and belumosudil, and emerging approaches like cell therapies and microbiome
strategies. We’ll also look at what day-to-day life can be like when you’re living with
GVHD treatment, with practical experience-based tips toward the end.

What Is GVHD and Why Is Treatment a Balancing Act?

GVHD happens after an allogeneic hematopoietic stem cell transplant (allo-HSCT), where
stem cells come from a donor rather than the patient. Donor immune cells (the graft)
recognize the recipient’s body (the host) as foreign and attack. GVHD most often affects
the skin, liver, gastrointestinal tract, eyes, lungs, and joints, and it ranges from
mild to life-threatening.

Clinically, doctors separate GVHD into:

• Acute GVHD: usually begins in the first 100 days after transplant, but it can appear later. It often targets skin, gut, and liver.
• Chronic GVHD: can start later (100–600 days or more after transplant) and may look more like an autoimmune disease, affecting many organs with scarring and long-term inflammation.

The treatment challenge is to:

• Control the immune attack so organs are protected.
• Preserve some graft-versus-leukemia activity.
• Prevent infections and other complications from long-term immunosuppression.
• Maintain the best quality of life possible.

Prevention First: How Doctors Try to Stop GVHD Before It Starts

GVHD “treatment” actually begins before the transplant with prevention strategies:

Donor Matching and Transplant Techniques

• HLA matching: The closer the match between donor and recipient tissue type, the lower the risk of GVHD, although risk never drops to zero.
• Conditioning regimens: The intensity and type of chemotherapy/radiation before transplant influence GVHD risk and severity.
• T-cell manipulation: Some centers use approaches that partially remove or modulate donor T cells to reduce GVHD, while trying to preserve immune function and graft-versus-leukemia benefits.

Standard GVHD Prophylaxis

Most patients receive medications from day zero to several months post-transplant to
prevent GVHD. Common combinations include:​

• Calcineurin inhibitors such as cyclosporine or tacrolimus.
• Short-course methotrexate or mycophenolate mofetil.
• Sometimes additional agents like sirolimus, ATG (anti-thymocyte globulin), or post-transplant cyclophosphamide (PTCy).

A major innovation has been post-transplant cyclophosphamide (PTCy), which is
given shortly after the transplant and has helped reduce GVHD and rejection, especially
in mismatched or haploidentical transplants.

Treatment of Acute GVHD

When GVHD does develop, the first step is to figure out:

• Which organs are affected (skin, gut, liver, others).
• How severe symptoms are, using standard grading systems (Grade I–IV).

Topical Therapy for Mild Skin-Only Disease

For Grade I acute GVHD, which typically involves only the skin, doctors may
start with:​

• Topical corticosteroids (creams/ointments) applied to rash areas.
• Moisturizers and gentle skin care to reduce itching and dryness.
• Close monitoring to catch any spread to gut or liver early.

First-Line Systemic Treatment: Corticosteroids

For more extensive skin involvement or any gut or liver GVHD, the standard first-line
systemic therapy is high-dose corticosteroids such as methylprednisolone or
prednisone. Typical starting doses are around 2 mg/kg/day, followed by a slow taper
over weeks if the disease responds.

Steroids work by dialing down the immune system broadly, which can quickly help:

• Calm skin rashes and blistering.
• Reduce gut inflammation that causes nausea, diarrhea, and abdominal pain.
• Lower liver inflammation and improve lab tests like bilirubin.

Most clinicians expect a clear response within 3–7 days. Unfortunately, about
35–50% of patients have steroid-refractory acute GVHD (their disease does not
improve or gets worse despite adequate steroid therapy).

Steroids are effective but far from perfect. Side effects can include:

• High blood sugar or diabetes.
• Increased infection risk.
• Muscle weakness, mood changes, weight gain, bone thinning, and more.

That’s why researchers have been working hard to find better, more targeted options
when steroids failor ideally, treatments that can reduce the amount of steroids
needed in the first place.

Second-Line and Newer Treatments for Steroid-Refractory Acute GVHD

Ruxolitinib: A New Standard for Steroid-Refractory aGVHD

Ruxolitinib is an oral JAK1/JAK2 inhibitor that targets key cytokine signaling
pathways driving inflammation in GVHD. Large clinical trials have shown that ruxolitinib
significantly improves response rates in patients whose acute GVHD does not respond to
steroids, and it is now considered the standard second-line therapy for steroid-refractory
disease.

Think of ruxolitinib as putting “noise-canceling headphones” on overactive immune
signaling. It doesn’t shut the immune system off completely, but it turns down the
volume so tissues can start to heal. Responses can be rapid, and some patients can
reduce their steroid doses sooner, which is a big win in terms of side effects and
quality of life.

Cell Therapy: Mesenchymal Stromal Cells (Ryoncil)

Another exciting option, particularly for children, is therapy with mesenchymal stromal
cells (MSCs). In 2024, the U.S. FDA approved Mesoblast’s MSC product,
Ryoncil, for pediatric patients (as young as 2 months) with steroid-refractory
acute GVHD. These cells, derived from healthy donor bone marrow, have potent
anti-inflammatory and tissue-repair properties.

MSCs are typically infused intravenously in multiple doses. They home to inflamed
tissues and release factors that calm immune overactivity and promote healing. While
not a cure-all, they offer a crucial option for children who have run out of standard
treatments.

Other Second-Line Options

Depending on the center and patient situation, additional therapies can include:​

• Extracorporeal photopheresis (ECP): treating white blood cells outside the body with a photosensitizing agent and UV light, then returning them to modulate the immune response.
• Additional immunosuppressants such as mycophenolate, sirolimus, or ATG.
• Biologic therapies targeting specific cytokines or immune cells (in clinical trials).
• Microbiome-based approaches, including fecal microbiota transplant, being investigated for gut GVHD.

Because the evidence for many of these options is still evolving, guidelines like those
from NCCN emphasize individualization and strong consideration of clinical trial
enrollment when possible.

Treatment of Chronic GVHD

Chronic GVHD (cGVHD) is now the leading cause of long-term non-relapse morbidity and
mortality after allo-HSCT. It can affect skin, eyes, mouth, lungs, liver, gut, and
joints, causing symptoms such as tight or thickened skin, dry mouth and eyes,
swallowing problems, lung scarring, and mobility issues.

First-Line Therapy: Steroids Plus Baseline Immunosuppression

Just as with acute GVHD, systemic corticosteroids are typically the first-line
therapy for cGVHD, often added on top of ongoing prophylactic agents like tacrolimus
or cyclosporine.

The goals are to:

• Control inflammation and symptoms (rashes, mouth sores, lung or liver involvement).
• Prevent progression to scarring and organ damage.
• Gradually taper steroids to avoid long-term complications.

Supportive care is critical: eye lubricants, oral rinses, physical and occupational
therapy, lung rehabilitation, and aggressive infection prevention all play major roles in
long-term outcomes and quality of life.

Targeted Therapies for Steroid-Refractory cGVHD

After decades of limited options, the last several years have seen an important wave of
FDA-approved targeted treatments for steroid-refractory chronic GVHD in both adults and
adolescents:​

• Ruxolitinib: Now approved for cGVHD after failure of one or two prior lines
  of systemic therapy. It modulates JAK/STAT signaling and has shown high overall
  response rates in both skin and internal organ involvement.
• Ibrutinib: A BTK inhibitor first approved for lymphomas and CLL, later
  approved as the first targeted agent for adult cGVHD not responding to standard
  therapy. It’s particularly useful when B-cell driven mechanisms are prominent.
• Belumosudil (Rezurock): A ROCK2 kinase inhibitor approved for patients
  12 years and older with cGVHD after failure of at least two prior systemic therapies.
  It has shown activity across multiple organs commonly affected in cGVHD, including
  skin, liver, lungs, gut, eyes, and joints.

These drugs don’t replace supportive care or the need to watch for infection, but they
offer new ways to control disease and may help patients reduce long-term steroid doses.

Other Therapies and Clinical Trials

Additional approaches used or studied for chronic GVHD include:​

• Extracorporeal photopheresis (ECP) for skin and lung involvement.
• Psoralen plus ultraviolet A (PUVA) light therapy for skin disease.
• Other immunosuppressants such as methotrexate, mycophenolate, sirolimus, and ATG.
• Emerging agents in clinical trials, including complement inhibitors, novel kinase inhibitors, and next-generation cell therapies.

Because chronic GVHD biology is complex, current NIH and international consensus
projects strongly encourage clinical trial participation whenever possible, especially in
severe or highly morbid forms of cGVHD.

Supportive Care: The Quiet Hero of GVHD Treatment

No matter which drug regimen is used, supportive care is absolutely central to
GVHD management. This includes:​

• Infection prevention: antiviral, antifungal, and antibiotic prophylaxis as appropriate; vaccinations at recommended times; rapid evaluation of fevers.
• Skin and mucosal care: fragrance-free products, barrier ointments, special mouth rinses, and careful sun protection.
• Eye care: preservative-free artificial tears, lubricating gels or ointments, and sometimes specialty contact lenses.
• Nutrition: working with a dietitian to maintain weight, muscle mass, and adequate protein and calories despite gut or mouth involvement.
• Rehabilitation: physical and occupational therapy to preserve strength, flexibility, and function in the face of joint stiffness, muscle weakness, or lung disease.
• Mental health support: counseling, peer groups, and psychiatric care when needed; GVHD and its treatments can be emotionally draining for patients and caregivers.

What to Expect: Real-World Experiences Living With GVHD Treatment

Reading about treatments in guideline tables is one thing; living with them day to day
is another. While every person’s experience is unique, many patients and caregivers
describe common themes as they navigate GVHD therapy.

The Roller Coaster of Steroids and Tapers

One of the first “life lessons” with GVHD is that steroid tapers rarely move in a straight
line. Many people start on high doses, feel better, then watch the dose drop slowly over
weeks or months. If symptoms flare, the dose may go back up. Emotionally, this can feel
like two steps forward and one step back.

Patients often say it helps to:

• Keep a symptom diary with notes about skin changes, bowel habits, fatigue, and mood.
• Use photos to track rashes or skin tightening, which makes it easier to show subtle changes to the care team.
• Ask early what the “ideal taper plan” looks like so you’re not surprised by changes, even if the plan later needs adjustment.

Learning a New Routine With Targeted Therapies

Starting a drug like ruxolitinib, ibrutinib, or belumosudil often comes with a mix of hope
and anxiety. On the plus side, many people appreciate that these are oral medications
that can be taken at home. On the other hand, they come with lab monitoring and
possible side effects like low blood counts, bruising, or infections.

Over time, patients commonly become experts in their own lab resultsknowing what their
“normal” looks like and asking good questions when something shifts. It’s incredibly
common to build a spreadsheet or notes app where you track:

• Medication doses and timing.
• Key lab values (like platelets, liver tests, or kidney function).
• Any new symptoms and when they started.

Care teams often encourage this level of involvement. GVHD follow-up is a marathon, not
a sprint, and shared decision-making works better when patients bring detailed
observations to each visit.

Managing Side Effects Without Losing Yourself

Long-term immunosuppression can change how you look and feelpuffy cheeks from steroids,
thinning hair, weight gain or loss, mood swings, and fatigue. Many people describe a
grieving process for their “old body” and “old energy level.” It’s not vain to care about
these changes; they affect identity and quality of life.

Strategies that often help include:

• Working with nutrition and rehab teams to build a realistic movement planeven 5–10 minutes of walking or stretching can be a win on low-energy days.
• Talking openly with the care team about mood, sleep, and anxiety; sometimes small medication adjustments or counseling can make a big difference.
• Setting tiny, achievable goals rather than chasing your pre-transplant self overnight.

Support Systems: You Shouldn’t Do This Alone

Many of the most powerful “treatments” for GVHD aren’t medications at allthey’re
support systems. Patients often credit spouses, parents, friends, and peer support
groups with helping them get through the roughest phases. Caregivers, in turn, need
their own outlets, breaks, and support networks to prevent burnout.

Transplant centers increasingly offer multidisciplinary GVHD clinics where hematologists,
dermatologists, pulmonologists, rehab specialists, and mental health providers work
together. When available, these services can reduce the feeling of being bounced from
one clinic to another and help create a unified plan.

Finding a New “Normal”

Perhaps the most honest expectation with GVHD treatment is that you may not return
exactly to life before transplant. Instead, many people talk about discovering a
“different normal.” That new normal might include daily medications, extra hand
hygiene, a mask in crowded spaces, or regular lung tests and physical therapy.

Over time, however, as doses decrease and disease comes under better control, life
usually feels less centered on GVHD and more on work, family, hobbies, and long-term
plans. Celebrating small milestonesfewer clinic visits, lower steroid doses, or the
first vacation after transplantcan be a powerful way to mark progress.

Key Takeaways

Treatment of graft-versus-host disease has evolved dramatically over the last decade.
Steroids and standard immunosuppression remain the backbone of therapy, but newer
targeted agents like ruxolitinib, ibrutinib, and belumosudil, along with cell-based
therapies such as MSCs, are reshaping outcomes for both acute and chronic GVHD.

At the same time, supportive care, rehabilitation, and mental health support are
just as important as any prescription. If you or a loved one is facing GVHD, staying
informed, asking questions, and leaning on your care team and support network can help
turn a frightening diagnosis into a more manageableif still challengingchapter of
recovery.

Finally, remember: this article is educational and cannot replace personalized medical
advice. Always discuss specific treatment decisions with your transplant and GVHD
specialists.