Chronic graft-versus-host disease (chronic GVHD or cGVHD) is a long-lasting problem that can happen after an allogeneic stem cell or bone marrow transplant. In this type of transplant, a person receives blood-forming stem cells from another person (the donor). In chronic GVHD, donor immune cells see the patient’s body as “foreign” and slowly attack many organs, causing long-term inflammation, scarring, and problems in daily life.
Chronic graft-versus-host disease is a long-term complication that can happen after an allogeneic (donor) stem-cell or bone-marrow transplant. Donor immune cells see the patient’s body as “foreign” and slowly attack organs such as the skin, mouth, eyes, liver, lungs, gut, joints and genitals, causing inflammation, scarring and organ damage. Symptoms usually start after 3–6 months but can appear later and may last for years. cGVHD is serious but treatable, and many people improve when treatment is started early and followed carefully.[1][2]
Chronic GVHD usually appears later than 3 months after transplant and can keep going for years. It can affect only one organ, but more often it affects several organs at the same time, such as skin, mouth, eyes, liver, lungs, gut, joints, or genital area. It is one of the main reasons for illness and death in people who have had an allogeneic transplant.
Doctors think of chronic GVHD as a kind of “autoimmune-like” disease. The donor immune system becomes out of balance, and instead of only fighting cancer cells or infections, it also attacks normal tissues. This leads to dryness, tight skin, stiff joints, breathing problems, liver problems, and many other symptoms if it is not controlled with treatment.
Other names of chronic GVHD
Chronic graft-versus-host disease can be found in medical books under a few similar names. These names all refer to the same or closely related conditions.
Some other names are:
Chronic graft-versus-host disease (cGVHD) – the most common short name in research and guidelines.
Chronic GvHD – same meaning, just a shorter spelling used in many articles.
Late graft-versus-host disease – used in some older texts to show that the problem starts later after transplant.
Autoimmune-like chronic GVHD – sometimes used to stress that the disease behaves like other autoimmune diseases such as scleroderma or Sjögren’s syndrome.
Types of chronic GVHD
Experts use different systems to group chronic GVHD. The National Institutes of Health (NIH) system is widely used. It helps doctors describe how the disease looks, which organs are involved, and how severe it is.
Main ways to describe types include:
By clinical pattern
Classic chronic GVHD – chronic GVHD signs without any signs of active acute GVHD.
Overlap chronic GVHD – when chronic GVHD signs are present together with features that look like acute GVHD.
By organ involvement
Skin-predominant chronic GVHD – main problems are rashes, thickened or tight skin, or changes similar to scleroderma.
Mouth (oral) chronic GVHD – main problems are dry mouth, pain, sores, or white patches in the mouth.
Eye (ocular) chronic GVHD – main problems are dry eyes, burning, gritty feeling, or blurred vision.
Liver chronic GVHD – main problems are abnormal liver blood tests and sometimes jaundice (yellow eyes and skin).
Lung chronic GVHD – often appears as bronchiolitis obliterans syndrome (BOS) with cough and breathlessness.
Gastrointestinal chronic GVHD – main problems are nausea, vomiting, abdominal pain, and diarrhea.
Muscle/joint/fascia chronic GVHD – causes muscle cramps, weakness, and very stiff joints or tight tissues.
Genital chronic GVHD – symptoms include pain, dryness, and sexual discomfort in both men and women.
By overall severity (NIH global score)
Mild – 1–2 organs involved, only mild symptoms.
Moderate – more organs involved or some organ scores in the middle range.
Severe – serious involvement of key organs such as lungs, or many organs with strong symptoms; this level is linked with worse survival.
Causes and risk factors
The basic “cause” of chronic GVHD is that the donor immune system reacts against the patient’s body after an allogeneic stem cell or bone marrow transplant. Many other things act as risk factors that make chronic GVHD more likely or more severe.
Allogeneic hematopoietic stem cell transplant itself
Chronic GVHD almost always happens only after an allogeneic transplant, where stem cells come from another person. The new immune cells from the donor can attack the patient’s tissues while trying to rebuild the immune system.History of acute GVHD
People who had moderate or severe acute GVHD soon after transplant have a higher chance of later developing chronic GVHD. Acute GVHD seems to “set up” long-term immune damage that can later become chronic.HLA mismatch between donor and recipient
HLA molecules are like ID cards on cells. When donor and recipient HLA types do not match well, donor immune cells see more of the recipient’s tissues as foreign, which increases the risk of chronic GVHD.Unrelated donor transplant
Receiving stem cells from an unrelated donor (instead of a matched brother or sister) increases the risk, because even with careful matching, there are more unseen differences that can trigger immune attack.Peripheral blood stem cell (PBSC) source
Using stem cells collected from the bloodstream rather than from bone marrow carries a higher rate of chronic GVHD. PBSC grafts contain more mature T-cells, which can drive the immune reaction.Older recipient age
Older patients have a higher risk of chronic GVHD. Their tissues may be more vulnerable to damage, and their immune system recovers more slowly and less precisely after transplant.Female donor to male recipient (especially multiparous women)
When a male patient receives stem cells from a woman who has been pregnant, the donor immune cells may recognize male-specific antigens and pregnancy-related antigens as foreign, increasing chronic GVHD risk.Higher intensity conditioning (strong chemotherapy or radiation)
Very strong conditioning before transplant damages tissues in the gut, skin, and other organs. This damage releases danger signals that activate donor immune cells and can promote chronic GVHD.Previous donor lymphocyte infusions (DLI)
Donor lymphocyte infusions are extra doses of donor T-cells used to fight relapse. These T-cells can also attack normal tissues and are linked to a higher risk of chronic GVHD.Non–T-cell-depleted graft (no strong T-cell removal)
If T-cells are not reduced in the graft, more donor immune cells enter the patient, which increases the chance of a graft-versus-host reaction becoming chronic.Cytomegalovirus (CMV) and other viral infections
Reactivation of viruses such as CMV after transplant causes strong immune activation and tissue injury. This extra immune stress is linked with a higher rate of chronic GVHD.Gut microbiome damage (loss of healthy bacteria)
Strong antibiotics, chemotherapy, and radiation damage gut bacteria. Loss of healthy microbiota can disturb immune balance in the intestine and increase GVHD risk.Delayed immune reconstitution and low regulatory T-cells
When protective regulatory T-cells (Tregs) recover slowly, they cannot calm down overactive donor T-cells. This imbalance between “attack” and “control” cells helps chronic GVHD develop.Genetic susceptibility in donor or recipient
Variations in genes that control immune responses and cytokines (chemical messengers) may make some people more likely to develop chronic GVHD after transplant.Type and level of GVHD prophylaxis drugs
If preventive immune-suppressing drugs are not strong enough, are stopped early, or are not well tolerated, donor T-cells may become more active and increase the risk of chronic GVHD.Previous severe tissue damage from infections or toxicity
Organs that were already damaged by infections, iron overload, or drug toxicity may be more easily targeted and injured by donor immune cells, encouraging chronic GVHD.ABO blood group mismatch
A mismatch in blood group between donor and recipient can add extra immune conflicts. This is a weaker factor than HLA mismatch but may still contribute to GVHD risk.Short time between transplant and immune complications
When complications such as acute GVHD or infections happen very early and are severe, they can trigger long-lasting immune problems that later appear as chronic GVHD.Chronic low-grade inflammation after transplant
Even small, ongoing inflammation (for example in the skin or gut) can keep donor immune cells activated. Over time, this can remodel tissues and produce chronic GVHD changes like fibrosis and thickening.Prolonged need for immune-suppressive drugs
People who need long periods of immune-suppressive treatment because of other complications may develop abnormal immune recovery patterns, making chronic GVHD more likely or more severe.
Symptoms of chronic GVHD
Chronic GVHD can look very different from person to person. Some people have only mild dryness or rash; others can have serious problems with movement, breathing, or eating.
Skin rash or redness
People may develop red or purple patches, bumps, or lines on the skin. The rash can be itchy, burning, or painful and often appears on the trunk, arms, or legs.Dry, flaky, or scaly skin
The skin may feel very dry, rough, or scaly, similar to severe eczema. This dryness makes the skin more likely to crack and become infected.Skin thickening and tightness (scleroderma-like changes)
In some people the skin becomes thick, shiny, and tight. This can limit movement of joints and give a “hard” feeling to the arms or legs, like in scleroderma.Changes in skin color
The skin may develop lighter (pale) or darker (brown) spots or patches. These color changes can follow old rash areas and may last for years.Itching and discomfort
Itching can be intense and constant, especially where the skin is dry or thick. Scratching may cause sores and infections, which add more discomfort.Dry mouth and trouble chewing or swallowing
Saliva glands can be damaged, leading to a very dry mouth, thick saliva, bad taste, and difficulty chewing or swallowing dry foods. Cavities become more common.Mouth sores, pain, or white patches
The lining of the mouth can develop painful sores, burning, or white lacy patches. Eating spicy, acidic, or rough foods can be very painful.Dry eyes and gritty or burning feeling
Damage to tear glands causes dry, burning, or gritty eyes, as if sand is inside them. People may be sensitive to light and have blurred vision.Cough and shortness of breath
When chronic GVHD affects the lungs, people may have a long-lasting dry cough, wheezing, or feel short of breath when walking or climbing stairs. This often reflects bronchiolitis obliterans syndrome.Nausea, vomiting, or stomach cramps
Involvement of the stomach and small bowel can cause ongoing nausea, vomiting, and crampy abdominal pain, especially after eating.Chronic diarrhea
Damage to the intestines can lead to frequent loose stools, urgent bowel movements, or weight loss due to poor absorption of food.Jaundice and dark urine
When the liver is affected, people may notice yellow skin or eyes, dark urine, pale stools, or itching. Blood tests often show abnormal liver enzymes.Muscle and joint pain or stiffness
Chronic GVHD can inflame muscles, joints, and fascia (tough tissues around muscles). This leads to pain, cramps, and stiffness, and in severe cases, fixed bending of joints (contractures).Genital dryness, irritation, or pain with sex
In both men and women, genital skin and mucosa can become dry, tight, and painful. People may have itching, burning, discharge, or pain during intercourse.Fatigue, weakness, and weight loss
Many patients feel very tired and weak due to chronic inflammation, poor nutrition, infections, and long-term use of immune-suppressive drugs. Unplanned weight loss is common.
Diagnostic tests for chronic GVHD
Doctors diagnose chronic GVHD using a careful mix of medical history, physical exam, and tests. The NIH criteria say that some signs are enough by themselves to make the diagnosis, while other “possible” signs need a supporting test such as a biopsy or special function test.
Physical exam tests
1. Full skin examination
The doctor looks closely at the whole skin surface, searching for rashes, color changes, thick areas, or tight, shiny skin. They also check nails and hair. The pattern and spread of skin changes help decide whether they match typical chronic GVHD features.
2. Oral cavity and throat examination
The doctor examines the mouth, tongue, cheeks, and throat using a light. They look for dryness, sores, ulcers, white lacy patches, and scarring. These findings are part of the NIH diagnostic scoring for oral chronic GVHD.
3. Eye examination at the bedside
Even before special tools are used, the doctor can check for redness, lack of tears, crusting, or conjunctival scarring. Simple questions about eye discomfort and light sensitivity help decide if more detailed eye tests are needed.
4. Joint range-of-motion assessment
The doctor gently moves the patient’s shoulders, elbows, wrists, hips, knees, and ankles. Limited movement, tight bands under the skin, or painful stiffness suggest fascia and joint involvement by chronic GVHD.
Manual / bedside functional tests
5. Two-minute walk test
In this simple test, the patient is asked to walk quickly but safely for two minutes. The doctor measures distance, heart rate, and breathlessness. Poor performance may reflect lung, muscle, or joint involvement from chronic GVHD.
6. Grip strength measurement
Using a hand-held device, the patient squeezes as hard as possible. Weak grip can result from muscle involvement, nerve problems, or general weakness caused by chronic GVHD and long-term steroid use.
7. Schirmer tear test
Small strips of paper are placed under the lower eyelids for a few minutes to measure tear production. Low wetting shows poor tear gland function and supports the diagnosis of ocular chronic GVHD.
8. Simple oral moisture and salivary flow checks
The doctor may time how long it takes for saliva to pool under the tongue or ask the patient to spit into a tube. Very low saliva supports mouth involvement and helps guide treatment.
Laboratory and pathological tests
9. Complete blood count (CBC) with differential
A CBC looks at red cells, white cells, and platelets. Chronic GVHD can cause low blood counts due to bone marrow involvement, long-term immunosuppression, or associated infections. Patterns in the CBC help guide further testing.
10. Liver function tests (LFTs)
Blood tests such as bilirubin, ALT, AST, ALP, and GGT are checked. Typical chronic GVHD liver involvement may show a cholestatic pattern with raised bilirubin and alkaline phosphatase, but patterns can vary.
11. Kidney and metabolic panel
Kidney function, electrolytes, and albumin are tested to look for organ involvement, drug toxicity, and nutritional status. Chronic GVHD and its treatments can affect many organ systems at once.
12. Inflammatory and immune markers
Markers such as C-reactive protein, immunoglobulin levels, and sometimes special cytokine panels can show ongoing inflammation and immune imbalance, although they are not specific to chronic GVHD.
13. Viral serology and PCR tests
Tests for CMV, hepatitis viruses, and other infections are important to rule out other causes of organ damage that can look similar to chronic GVHD, especially in the liver and gut.
14. Tissue biopsy (skin, mouth, liver, gut, lung, or genital)
A small sample of tissue is taken and examined under a microscope. Typical patterns (such as interface dermatitis in skin or bile duct damage in liver) can strongly support the diagnosis when combined with clinical signs.
Electrodiagnostic tests
15. Nerve conduction studies (NCS)
If patients have numbness, tingling, or weakness, nerve conduction tests measure how fast electrical signals travel along nerves. Chronic GVHD-related neuropathy may show slower or blocked conduction in affected nerves.
16. Electromyography (EMG)
EMG uses small needles to record electrical activity in muscles at rest and during movement. It helps distinguish muscle disease, nerve disease, or joint problems and can document involvement of muscles in chronic GVHD.
Imaging tests
17. Chest X-ray
A plain chest X-ray is often the first imaging test if there is cough or breathlessness. It can show lung scarring, infections, or other changes that suggest lung involvement from chronic GVHD or other problems.
18. High-resolution CT (HRCT) scan of the lungs
HRCT gives detailed images of small airways and lung tissue. In chronic GVHD, it may show air-trapping, bronchial wall thickening, or other signs of bronchiolitis obliterans syndrome.
19. Abdominal ultrasound or CT scan
Imaging of the liver and biliary tree can help rule out gallstones, bile duct problems, or tumors. When combined with blood tests and sometimes biopsy, it supports the diagnosis of liver chronic GVHD.
20. Barium swallow or esophagram
If there is difficulty swallowing, a contrast X-ray study of the esophagus can show rings, strictures (narrow areas), or poor movement that may be due to chronic GVHD related scarring.
Non-pharmacological treatments
1. Patient education and self-monitoring
Learning what cGVHD is, which organs can be affected, and which warning signs to watch for helps patients and families react early. Education includes understanding medicines, how to take them correctly, and what side effects need urgent care. Simple tools like symptom diaries, photos of skin changes, and lung-function or weight tracking make it easier to show changes to the transplant team. Good education reduces fear, improves treatment adherence, and can prevent serious complications by catching problems sooner.[1][3]
2. Infection-prevention and hygiene routines
Because cGVHD usually requires long-term immune-suppressing treatment, infections are a major risk. Daily hand-washing, alcohol gel, mask use in crowded or high-risk places, avoiding sick contacts, safe food handling, and dental hygiene all lower infection risk. Families are often advised to avoid raw eggs, raw fish and unpasteurised products, and to clean bath and kitchen areas regularly. These simple habits do not treat cGVHD directly, but they protect weakened immunity and reduce hospital admissions and treatment interruptions.[1]
3. Sun protection and gentle skin care
Skin is the most commonly affected organ in cGVHD, and ultraviolet (UV) light can worsen rashes, thickening and pigment changes. Daily broad-spectrum sunscreen, protective clothing, hats and shade reduce UV damage. Gentle, fragrance-free moisturisers help repair the skin barrier and reduce itching and cracking. Avoiding harsh soaps, hot showers and scratching also protects fragile skin. Good skin care improves comfort and may reduce scarring and stiffness.[2][4]
4. Physical therapy and stretching
cGVHD can cause tight skin, fascia and joint stiffness, especially in the shoulders, elbows, wrists, ankles and fingers. Regular physiotherapy uses stretching, range-of-motion exercises, strengthening and posture training to keep joints moving and prevent contractures. Home exercise programmes, splints and braces may be used to maintain function between visits. Early and continuous movement helps patients walk, dress and do daily activities more easily, and can limit permanent disability.[5]
5. Occupational therapy and hand therapy
Occupational therapists focus on everyday tasks such as writing, cooking, using phones and self-care. They can provide hand exercises, adaptive tools (special pens, grips, utensils), and advice on pacing activities to reduce fatigue and pain. For people with severe sclerotic skin or joint problems, splints and custom braces may prevent deformity. This support helps patients stay independent at home, school or work despite long-term illness.[6]
6. Pulmonary rehabilitation and breathing exercises
Lung involvement (bronchiolitis obliterans) can cause cough, wheeze and breathlessness in cGVHD. Pulmonary rehab programmes include breathing exercises, inhaler-technique training, airway-clearance methods, and graded aerobic exercise like walking or cycling. Education about avoiding smoke, dust and strong fumes is also important. These non-drug methods help maintain lung function, improve stamina, and reduce anxiety around shortness of breath.[1]
7. Eye lubrication and protective eye care
Dry eye disease is common in cGVHD because tear glands and eyelids become inflamed and scarred. Regular use of preservative-free artificial tears, gels and ointments keeps the eye surface moist and reduces pain, burning and light sensitivity. Moisture goggles, humidifiers and avoiding fans or smoke also help. Severe cases may use punctal plugs or scleral lenses (devices that hold fluid over the eye), which are still non-drug, device-based treatments. Early eye care prevents corneal damage and vision loss.[7]
8. Oral care and dental support
Mouth cGVHD can cause dryness, ulcers, sensitivity and difficulty eating. Gentle tooth-brushing with a soft brush, alcohol-free mouthwashes, frequent sips of water, sugar-free gum, and saliva substitutes protect teeth and gums. Regular dental checks allow early treatment of cavities and infections. Avoiding tobacco, alcohol mouth-rinses and irritating foods (very spicy, acidic) reduces pain. Good oral care helps maintain nutrition, speech and quality of life.[6]
9. Sexual health, genital care and pelvic physiotherapy
Genital cGVHD can cause dryness, pain, tightness and scarring in the vagina or foreskin, making sex and exams painful. Regular gentle moisturisers, lubricants, vaginal dilators and pelvic-floor physiotherapy can keep tissues flexible and reduce pain. Psychosexual counselling supports couples in talking about intimacy and body changes. These non-drug approaches can be combined with local hormone or steroid treatments when needed, guided by specialists.[5]
10. Nutrition counselling
cGVHD and its medicines can cause weight loss, muscle wasting, taste changes and gut symptoms. Dietitians help plan high-protein, energy-dense meals and snacks that are gentle on the gut (for example, soft foods, low-fat, low-acid options). They may suggest lactose-free or low-fibre periods during flares. Hydration planning and food-safety advice are included. Individual nutrition plans support healing, maintain strength and reduce hospital stays.[2]
11. Psychological counselling and support groups
Living with long-term cGVHD can lead to low mood, anxiety, body-image concerns and family stress. Psychologists, social workers and counsellors can teach coping skills, relaxation techniques and problem-solving tools. Peer groups (face-to-face or online) let patients share experiences and practical tips. Addressing mental health early improves treatment adherence, reduces isolation and supports the whole family.[3]
12. Structured exercise and fatigue management
Simple, regular movement such as walking, light cycling or resistance bands is safe for many patients when guided by the transplant team. Exercise helps maintain muscle mass, bone density, heart health and mood. Fatigue-management strategies include pacing, planned rest, and prioritising important activities. A balanced approach avoids both over-exertion and complete inactivity, which can worsen weakness and stiffness.[1]
13. Extracorporeal photopheresis (ECP)
ECP is a non-surgical procedure often classed as a “cell-based” therapy. Blood is taken from the patient, white cells are separated, treated with a light-sensitising medicine, exposed to ultraviolet light in a machine, and then returned. This process changes immune cells so they are less aggressive but still protect against cancer. ECP is widely used for steroid-refractory or steroid-dependent cGVHD, especially with skin and lung involvement, and can reduce steroid doses over time.[8][9]
14. Telemedicine and coordinated long-term follow-up
Because cGVHD can last for years, regular follow-up with a multidisciplinary team (transplant, dermatology, lung, eye, rehab, dentistry, psychology) is vital. Telemedicine visits, shared electronic records and clear care plans help coordinate this complex care. Early review when symptoms change allows rapid treatment adjustments, which can prevent flares from becoming severe.[10]
15. Sleep hygiene strategies
Sleep disturbance is common in long-term illness and can worsen pain, fatigue and mood. Non-drug sleep strategies include regular sleep and wake times, reducing late caffeine, limiting screens before bed, and creating a quiet, dark bedroom. Relaxation exercises or breathing techniques at bedtime can also help. Better sleep improves energy, thinking and coping with chronic symptoms.[1]
16. Smoking cessation and avoiding lung irritants
Smoking and second-hand smoke damage lungs and blood vessels and are especially harmful in people with lung cGVHD. Quitting smoking, avoiding vaping, and staying away from dust, strong chemicals and pollution protect already-inflamed airways. Support programmes, counselling and nicotine-replacement (a drug) can be added, but the main concept is lifestyle change and lung protection.[1]
17. Protective equipment and ergonomic adjustments
Simple aids such as walking sticks, grab bars, shower chairs, anti-slip mats and raised toilet seats can make daily life safer when balance, strength or joints are affected. At work or school, ergonomic chairs, adjustable desks and keyboard supports reduce strain and pain. These changes do not treat the immune process but help patients stay active and independent with fewer falls and injuries.[3]
18. Scar management and massage
In some patients, cGVHD causes thick, tight scars (sclerotic skin). Under professional guidance, massage, stretching, silicone sheets and pressure garments can soften scars and improve flexibility. Scar management is usually combined with physical therapy and medical treatment. The goal is to reduce pain, improve appearance and keep joints moving as well as possible.[14]
19. School or work reintegration planning
Returning to school or work is a major step in recovery. Planning might include part-time schedules, extra breaks, remote work or study, and help with transport. Teachers and employers can be informed (with permission) about infection risks and fatigue. A structured plan supports social life, independence and mental health while respecting medical limits.[3]
20. Palliative care and advanced-care planning
Palliative care in cGVHD is not only for end-of-life; it focuses on symptom control, emotional support and aligning treatment with personal goals. Teams may help with pain, itch, breathlessness, anxiety and complex decisions. Advanced-care planning lets patients state their wishes about future treatments. Using palliative care early can improve quality of life and reduce distress for patients and families.[10]
Drug treatments
Important: Doses below are typical label-based or commonly used starting doses in adults. Exact dose, schedule and combinations must be chosen and adjusted only by the transplant team, based on age, kidney and liver function, and other illnesses. Never start, stop or change these medicines on your own.
1. Prednisone (systemic corticosteroid)
Prednisone is the standard first-line medicine for most moderate or severe cGVHD. A common starting dose is about 0.5–1 mg per kg of body weight once daily, then slowly tapered as symptoms improve. It works by broadly calming down the immune system and reducing inflammation in skin, liver, gut and other organs. Side effects include weight gain, high blood sugar, mood change, bone loss, muscle weakness and higher infection risk, so long-term use is carefully monitored.[1]
2. Topical corticosteroids (creams, ointments, mouth rinses)
Strong steroid creams or ointments can treat local skin rashes, thick plaques and itch, while steroid mouth rinses help painful mouth lesions. They work by calming local inflammation with less whole-body effect than tablets, especially when used on limited areas. Side effects include skin thinning, stretch marks and mouth fungal infections if over-used, so doctors usually limit strength, area and duration.[4]
3. Tacrolimus (systemic calcineurin inhibitor)
Tacrolimus is an immunosuppressive drug often combined with steroids in cGVHD. It blocks calcineurin, a key enzyme in T-cell activation, reducing the immune attack on tissues. Oral doses are adjusted to reach target blood levels, usually taken twice daily. Side effects include kidney problems, high blood pressure, tremor, headache, high potassium and increased infection risk, so labs and levels are checked regularly.[13]
4. Cyclosporine (systemic calcineurin inhibitor)
Cyclosporine works in a similar way to tacrolimus and has been used for decades in GVHD prevention and treatment. It is usually given twice daily by mouth, with doses adjusted to blood levels and kidney function. Side effects include kidney damage, high blood pressure, gum overgrowth, hair changes and increased infection risk. Doctors may choose cyclosporine or tacrolimus based on centre experience and patient factors.[13]
5. Mycophenolate mofetil (MMF)
Mycophenolate blocks an enzyme that lymphocytes need to make DNA, so it slows the growth of immune cells attacking the host. It is usually given twice daily by mouth. Common side effects include diarrhoea, nausea, low white blood cells and infection risk, and it can harm an unborn baby, so effective contraception is needed. MMF is often used when steroids and calcineurin inhibitors are not enough or cause too many side effects.[11]
6. Sirolimus (mTOR inhibitor)
Sirolimus targets mTOR, a pathway involved in cell growth and T-cell activation. In cGVHD it can be used alone or with other drugs, especially when calcineurin inhibitors cause kidney problems. It is taken orally once daily and requires blood-level monitoring. Side effects can include high cholesterol, mouth ulcers, delayed wound healing, low blood counts and lung inflammation.[11]
7. Methotrexate (low-dose immunosuppressant)
Low-dose methotrexate, taken weekly, interferes with folate metabolism in rapidly dividing cells including immune cells. It is sometimes used for joint and skin involvement, similar to its use in rheumatoid arthritis. Side effects include mouth sores, liver irritation, low blood counts and lung toxicity, so folic acid supplementation and regular blood tests are essential. Alcohol intake is usually limited while on this drug.[13]
8. Azathioprine
Azathioprine is an older immunosuppressant that interferes with DNA synthesis in lymphocytes. It may be used as a steroid-sparing agent in some cGVHD regimens, though concerns about infections and secondary cancers mean it is used cautiously. Regular blood tests are needed to monitor white cells and liver function. Genetic testing for TPMT / NUDT15 enzyme activity may be considered to reduce toxicity risk.[13]
9. Ruxolitinib (Jakafi – JAK1/2 inhibitor, FDA-approved for cGVHD)
Ruxolitinib blocks Janus kinase (JAK1/2) signalling, which plays a key role in inflammatory cytokine pathways. The FDA approved it for steroid-refractory cGVHD after failure of one or two lines of systemic therapy in adults and children ≥12 years, based on trials showing response rates around 60–70%.[5] A common adult starting dose is 10 mg twice daily, adjusted for kidney, liver function and blood counts. Side effects include low red and white cells, infections, bruising, high cholesterol and rare serious events like blood clots.[5]
10. Belumosudil (Rezurock – ROCK2 inhibitor, FDA-approved for cGVHD)
Belumosudil is a selective ROCK2 kinase inhibitor that modulates immune pathways and fibrosis. The FDA approved it for adults and children ≥12 years with cGVHD after at least two prior lines of systemic therapy.[6][7] The recommended dose is 200 mg once daily with food until disease progression or unacceptable toxicity. Common side effects include infections, nausea, diarrhoea, tiredness, cough, shortness of breath, high blood pressure, and abnormal liver or phosphate tests.[6]
11. Ibrutinib (Imbruvica – BTK inhibitor, FDA-approved for cGVHD)
Ibrutinib blocks Bruton tyrosine kinase (BTK), which is important in B-cell signalling. It was the first FDA-approved therapy for adults with cGVHD after failure of at least one prior systemic therapy, and approval has been extended to children ≥1 year, including an oral suspension form.[8][9] A common adult dose is 420 mg orally once daily. Side effects include diarrhoea, bleeding, infections, heart rhythm problems, high blood pressure and low blood counts.[8]
12. Rituximab (anti-CD20 monoclonal antibody)
Rituximab targets CD20 on B-cells, leading to their depletion. It is used off-label in some forms of cGVHD, especially with strong B-cell or autoantibody involvement. It is given by intravenous infusion at intervals (for example weekly for 4 doses). Side effects include infusion reactions, low immunoglobulin levels, infections and rare severe brain infection (PML). Vaccines are less effective while B-cells are depleted.[11]
13. Topical calcineurin inhibitors (tacrolimus, pimecrolimus creams)
These creams are used for local skin or mucosal lesions, including around the mouth or genitals, when steroid side effects are a concern. They block calcineurin locally, reducing T-cell activation without thinning the skin. Burning or stinging at application sites is common; systemic absorption is usually low but caution is still needed. They are often combined with moisturisers and gentle skin care.[4]
14. Inhaled and nebulised corticosteroids / bronchodilators
For bronchiolitis-obliterans-type lung cGVHD, inhaled steroids and bronchodilators may be used similar to asthma or COPD management. They deliver medicine directly to the lungs with fewer body-wide effects. Side effects can include hoarseness, oral thrush and tremor, so mouth-rinsing after use is advised. They are usually part of a wider lung-care plan including rehab and systemic therapy.[1]
15. Ursodeoxycholic acid
Ursodeoxycholic acid is a bile acid used in cholestatic liver disease. In cGVHD with liver involvement it may improve bile flow, reduce itching and protect liver cells, especially when combined with immunosuppressants. It is usually taken twice daily with food. Side effects are often mild and include diarrhoea and abdominal discomfort.[1]
16. Systemic antifungals and antivirals (supportive)
Medicines such as fluconazole, posaconazole, aciclovir or valganciclovir do not treat cGVHD directly but prevent or treat serious opportunistic infections while the immune system is suppressed. Doses depend on body weight and kidney function. Side effects may include liver-test changes, kidney problems, low blood counts and drug interactions, so they are closely monitored by the transplant team.[1]
17. Proton-pump inhibitors (PPIs)
Drugs like omeprazole reduce stomach acid and help protect the gut lining, especially in patients taking steroids and other medicines that irritate the stomach. They may also reduce reflux-related symptoms in oesophageal involvement. Long-term PPI use can increase risks of low magnesium, bone thinning and certain infections, so they are used at the lowest effective dose.[1]
18. Antihistamines and anti-itch medicines
Non-sedating antihistamines during the day, and sedating ones at night, can help control itch and improve sleep in skin cGVHD. They block histamine’s effect on nerve endings and blood vessels. Side effects include drowsiness (for older agents), dry mouth and, rarely, heart-rhythm changes. They are usually combined with moisturisers and topical therapies.[4]
19. Pain-management medicines
Paracetamol, certain neuropathic-pain medicines (for example, gabapentin) and, in selected cases, opioids may be used for pain from skin tightening, nerve damage or procedures. Doses and combinations must be individualised and re-evaluated regularly. Side effects include drowsiness, constipation, nausea and dependence risk with opioids, so non-drug methods are always considered too.[3]
20. Combination regimens and clinical-trial medicines
In real life, cGVHD treatment often uses combinations such as steroids plus ruxolitinib, or belumosudil with extracorporeal photopheresis, guided by new research and guidelines.[9][10] Many other targeted drugs are under study in clinical trials. Your transplant centre may suggest a trial if standard options are not enough. Risks and benefits are carefully explained before consent.[9]
Dietary molecular supplements
Always discuss supplements with the transplant team, as some may interact with immunosuppressive drugs or be contraindicated.
Vitamin D – Chronic GVHD, steroids, and reduced sunlight can lead to low vitamin D, which weakens bones and may alter immunity. Supplementation aims to reach sufficient blood levels, typically using daily or weekly oral doses tailored to lab results. Vitamin D supports calcium balance, bone mineralization, and immune modulation, helping reduce fracture risk and possibly influencing inflammatory activity.
Calcium – Long-term steroids increase the risk of osteoporosis and fractures, so calcium intake from diet and supplements is often boosted. Calcium with vitamin D helps support bone strength but must be balanced to avoid kidney stones or vascular calcification. Doses are individualized based on diet, kidney function, and other medicines.
Omega-3 fatty acids (EPA/DHA) – Omega-3 fats from fish oil capsules or enriched foods have anti-inflammatory effects and may help with gut inflammation, metabolic complications, and cardiovascular risk. Typical supplemental doses are a few grams per day, but they can increase bleeding risk at high doses, especially in patients on antiplatelet or anticoagulant drugs.
Zinc – Zinc deficiency is common in patients with gut GVHD due to diarrhea and malabsorption. Replacement, guided by blood tests, may improve taste, appetite, wound healing, and immune function. Excess zinc can interfere with copper balance, so dosing must be monitored.
Vitamin A – Vitamin A is important for mucosal integrity and immune balance, and deficiencies may occur in severe gut GVHD. Carefully dosed supplementation can support gut and eye health, but high doses are toxic to the liver and nervous system, so medical supervision is essential.
Vitamin B12 and folate – Chronic illness, reduced intake, and certain drugs can lower B12 and folate levels. Correcting deficiencies supports red-blood-cell production, nerve function, and energy levels. Supplementation is usually oral but may be injectable in severe malabsorption, and dosing is guided by lab testing.
Probiotics (selected strains) – Some studies suggest that specific probiotic strains may help maintain or restore a healthy gut microbiome, which could influence GVHD activity. However, in severely immunosuppressed patients there is a small risk of probiotic-related infections, so choices must be made cautiously and under specialist guidance.
Glutamine – Glutamine is an amino acid fuel for intestinal cells and may help maintain gut barrier function during severe gut inflammation. Supplemental glutamine is sometimes used in clinical nutrition protocols, although evidence is mixed, and dosing depends on kidney function and overall protein intake.
High-protein nutritional drinks or powders – Specialized high-protein formulas support muscle mass and healing when appetite is poor or chewing is difficult. They can be adjusted for low fat, low lactose, or low fiber to match GVHD diet restrictions while still meeting protein targets. Dietitians help integrate these supplements into daily eating plans.
Electrolyte solutions (oral rehydration) – During gut flares with diarrhea or vomiting, oral rehydration solutions containing sodium, potassium, and glucose help prevent dehydration and maintain blood pressure. Commercial preparations or hospital-recommended recipes are safer than sugary soft drinks or plain water alone. Doses are adjusted to stool losses and lab results.
Immunity-boosting, regenerative and stem-cell–related drugs
Recombinant human growth factors (G-CSF, GM-CSF)
These injected medicines stimulate the bone marrow to produce more white blood cells, especially neutrophils, which can reduce serious bacterial and fungal infections during intensive immunosuppression. They do not directly treat chronic GVHD but support the immune system when blood counts fall too low from drugs or disease. Side effects include bone pain and, rarely, splenic enlargement or respiratory symptoms.Thrombopoietin receptor agonists (eltrombopag, romiplostim)
In cases of severe thrombocytopenia after transplant, these drugs stimulate platelet production and can reduce bleeding risk. They may be used alongside chronic GVHD treatment when marrow function is suppressed. Doses are adjusted based on platelet counts, and side effects include liver enzyme elevations and, rarely, clotting events.Mesenchymal stromal cell (MSC) therapies (investigational)
MSC infusions are being studied as regenerative and immunomodulatory treatments in GVHD. These cells can home to inflamed tissues, secrete anti-inflammatory factors, and support tissue repair. While some centers use them in clinical trials or selected cases, they are not yet standard for chronic GVHD, and long-term safety and efficacy are still being defined.Low-dose interleukin-2 therapy (experimental tolerance induction)
Low-dose IL-2 is being investigated to expand regulatory T cells, which help calm harmful immune responses without fully suppressing protective immunity. Early studies suggest possible benefits in chronic GVHD, but it remains a research-level therapy rather than routine practice. Side effects may include flu-like symptoms, injection-site reactions, and lab changes.Second allogeneic transplant or stem-cell boost (very selected cases)
In rare situations of graft failure or severe complications, a stem-cell boost or second transplant may be considered to re-establish a healthier immune system. This approach carries major risks, including severe acute and chronic GVHD, infections, and organ damage, so it is reserved for carefully chosen patients after detailed risk-benefit discussions.Clinical-trial agents targeting novel pathways
Many new agents (for example, other JAK inhibitors, BTK inhibitors, ROCK inhibitors, and antibodies against specific immune cells or cytokines) are under study for chronic GVHD. Participation in clinical trials gives access to these regenerative or immune-reprogramming approaches under close monitoring. This also helps advance knowledge and future treatment options for chronic GVHD worldwide.
Surgeries and procedures
Bronchoscopic interventions for airway stenosis
In advanced lung GVHD, some patients develop localized airway narrowing that may benefit from bronchoscopic balloon dilation or stent placement. These procedures aim to relieve obstruction, improve airflow, and reduce symptoms like wheeze and breathlessness. They are usually combined with ongoing medical therapy and pulmonary rehab.Ocular surface surgeries (punctal plugs, amniotic membrane grafts)
For severe dry eye with corneal damage, ophthalmic procedures such as punctal plug insertion, tarsorrhaphy (partial eyelid closure), or amniotic membrane grafts may be needed. These surgeries help preserve vision, reduce pain, and protect the cornea from ulceration or perforation. Long-term follow-up remains essential, as chronic GVHD eye disease can fluctuate.Contracture-release surgery and skin grafting
When skin and fascia become very tight, causing fixed contractures that do not respond to therapy, surgical release of scar tissue and sometimes skin grafting may restore some movement. Surgery is usually considered only after inflammation is controlled and rehabilitation has reached a plateau. Post-operative physical therapy is critical to maintain gains in range of motion.Gynecologic reconstructive procedures
Severe genital GVHD can lead to vaginal stenosis, adhesions, or scarring that interferes with menstruation, sexual function, and pelvic examinations. Gynecologic surgeries to release adhesions or reconstruct the vaginal canal may be needed in selected cases, combined with topical therapies and dilator programs. Careful timing and long-term follow-up are important to prevent re-scarring.Feeding tube placement (gastrostomy or jejunostomy)
When swallowing is unsafe or oral intake remains inadequate despite diet changes, placement of a feeding tube into the stomach or small intestine can provide long-term nutritional support. This procedure helps maintain weight and muscle mass while gut GVHD heals and systemic therapy continues. Risks include infection, tube dislodgement, and irritation, so home-care training is essential.
Prevention of chronic GVHD
Careful donor selection and HLA matching – Better HLA matching and consideration of donor characteristics (age, sex, parity) lower the baseline risk of chronic GVHD.
Optimized GVHD prophylaxis after transplant – Use of combinations like calcineurin inhibitors plus methotrexate or post-transplant cyclophosphamide helps reduce acute and chronic GVHD rates.
Appropriate stem-cell source choice – Peripheral-blood stem cells carry a higher chronic GVHD risk than bone marrow; choice is individualized based on disease and donor factors.
Early detection and treatment of acute GVHD – Prompt control of acute GVHD may reduce progression to chronic GVHD, so early reporting of skin rashes, gut symptoms, or liver abnormalities is vital.
Infection prevention and vaccination – Preventing severe infections and inflammation can limit immune activation that might trigger or worsen chronic GVHD.
Steroid-sparing strategies to avoid overtreatment and undertreatment – Appropriate use of new targeted drugs reduces long-term steroid exposure while improving disease control, which may prevent chronic scarring.
Lifestyle measures (no smoking, healthy weight, physical activity) – General health supports organ reserve and may reduce complications from chronic GVHD and its treatments.
Education about early warning signs – Teaching patients to recognize dry eyes, mouth ulcers, skin tightening, cough, or weight loss encourages early clinic visits before damage becomes irreversible.
Regular surveillance with organ-specific assessments – Scheduled lung function tests, eye exams, oral exams, and skin checks allow detection of subclinical chronic GVHD.
Participation in clinical trials and registries – Contributing to research helps refine prevention strategies and personalize prophylaxis for future patients.
When to see a doctor urgently
People living after an allogeneic transplant should contact their transplant team or seek urgent care if they notice any new or rapidly worsening symptoms, such as spreading skin rash, severe dryness or pain in eyes or mouth, persistent diarrhea or vomiting, jaundice, shortness of breath, new wheeze or cough, chest pain, fevers or chills, sudden weight loss, or difficulty moving joints due to tightening skin. Any sign of infection, bleeding, confusion, or severe weakness deserves immediate attention, because chronic GVHD and its treatments can quickly become life-threatening without early intervention. It is safer to call the transplant team too early than to wait too long.
What to eat and what to avoid
Prefer soft, bland, low-acid foods during gut flares – Foods like plain rice, pasta, bananas, potatoes, scrambled eggs, and lean chicken are usually better tolerated than spicy, acidic, or fried meals when gut GVHD is active.
Limit fat and fiber in early phases of gut healing – A low-fat, low-fiber diet reduces mechanical irritation of the intestine and may ease diarrhea and cramping until the gut improves.
Avoid lactose if dairy triggers symptoms – Many patients with gut GVHD become temporarily lactose-intolerant, so lactose-free milk or plant-based alternatives are often better options.
Choose safe, well-cooked foods and practice food hygiene – To reduce infection risk, patients should avoid raw eggs, raw meat or fish, unpasteurized products, and salad bars, and should follow strict kitchen hygiene practices.
Drink enough fluids, using oral rehydration solutions if needed – Small, frequent sips of water, weak tea, clear broths, or oral rehydration drinks help prevent dehydration during diarrhea or vomiting episodes.
Focus on adequate protein intake – Lean meats, eggs, tofu, yogurt alternatives, and protein supplements help maintain muscle mass and support healing, especially while on steroids.
Limit highly spicy, fried, or greasy foods – These foods can aggravate gut symptoms, indigestion, and reflux in both upper and lower GI GVHD.
Reduce caffeine and alcohol – Caffeine can worsen diarrhea and sleep problems, while alcohol can irritate the liver and gut and interact with medicines, so both are usually limited or avoided.
Avoid grapefruit and some herbal products that interact with drugs – Grapefruit and certain herbal supplements can change blood levels of calcineurin inhibitors and targeted agents, making them unsafe without medical supervision.
Work closely with a transplant dietitian – Individual needs change over time; dietitians adjust plans as symptoms, weight, and lab values evolve, ensuring both safety and enjoyment of food.
Frequently asked questions (FAQs)
Is chronic GVHD a type of autoimmune disease?
Chronic GVHD behaves like an autoimmune disease because donor immune cells attack the patient’s tissues and cause long-lasting inflammation and scarring in many organs. However, it is specifically triggered by allogeneic transplant and has unique patterns and treatments that differ from classic autoimmune diseases like lupus.Can chronic GVHD be cured completely?
Some people experience complete remission and can stop all immunosuppressive medicines, while others have partial control with low-dose therapy or develop stable but permanent organ changes. The chance of “cure” depends on severity, organs involved, response to therapy, and complications like infections or lung fibrosis.How long does treatment usually last?
Treatment often lasts for years, and many patients need gradual tapering of steroids and other drugs over a long period to avoid flares. Some people remain on low-dose targeted therapy or immunosuppression for persistent disease, while others can eventually stop all treatment under close supervision.What are the most serious complications of chronic GVHD?
Serious complications include severe lung disease (bronchiolitis obliterans), liver failure, recurrent serious infections, eye damage leading to vision loss, and disability from skin and fascial tightening. These risks are related to both the disease and long-term immunosuppressive therapy.How do newer drugs like ibrutinib, ruxolitinib, belumosudil, and axatilimab help?
These targeted agents work on specific signaling pathways in immune cells and fibrotic processes, offering more focused control of chronic GVHD with potential steroid-sparing benefits. Clinical trials and FDA approvals have shown meaningful response rates in patients who failed previous therapies, although side effects and long-term outcomes require careful monitoring.Will chronic GVHD always get worse over time?
No. In some people it stabilizes or improves, especially with appropriate treatment and rehabilitation, while in others it remains active or progresses. Regular follow-up, early adjustment of therapy, and aggressive management of complications help tilt the balance toward improvement.Can I work, study, or exercise with chronic GVHD?
Many patients return to work, school, and physical activity, but may need adjustments such as flexible schedules, lighter tasks, or tailored exercise programs. Coordination between the medical team, rehabilitation specialists, and workplace or school staff is key to a safe and sustainable plan.Does chronic GVHD mean my original cancer is more or less likely to return?
Chronic GVHD is linked to the “graft-versus-leukemia” effect, which can lower relapse risk for some blood cancers, but it also brings significant morbidity. Overall risk of relapse depends on many factors, including cancer type, disease status at transplant, and donor characteristics, so your transplant team is best placed to explain your individual risk.Are vaccines safe for people with chronic GVHD?
Most inactivated vaccines are safe and recommended on a specific schedule after transplant, even in people with chronic GVHD, to protect against serious infections. Live vaccines are usually avoided until immune recovery is strong and immunosuppression is minimal, and decisions are always individualized.Can diet alone control chronic GVHD?
Diet is very important for comfort, healing, and preventing malnutrition, especially when the gut is affected, but it cannot replace immunosuppressive or targeted drugs. Nutritional care works together with medical treatment to improve overall health and tolerance of therapy.Is chronic GVHD the same as late acute GVHD?
No. Late acute GVHD refers to acute-type symptoms that appear later after transplant, while chronic GVHD has different diagnostic criteria and often involves scarring and autoimmune-like features. However, some patients can have overlapping features of both, which can complicate diagnosis and treatment.Can chronic GVHD affect mental health?
Yes. Long-lasting illness, visible changes, fatigue, and uncertainty can cause anxiety, depression, and stress for patients and families. Early access to psychological support, peer groups, and honest communication about expectations can greatly improve coping and quality of life.What is the role of clinical trials for someone with chronic GVHD?
Clinical trials offer access to new therapies and combinations that might work when standard options are limited, and also help improve future care. Your transplant team can advise which trials fit your disease stage, previous treatments, and health status.How often should I see my transplant team if I have chronic GVHD?
Visit frequency depends on severity and stability but is usually more frequent during active disease or treatment changes and less frequent during stable remission. Even if you feel well, long-term follow-up is necessary to check organs, adjust medicines, update vaccines, and screen for late effects such as secondary cancers or bone disease.What is the most important thing I can do as a patient?
The most important actions are staying engaged with your transplant team, reporting new symptoms early, taking medicines exactly as prescribed, following infection-prevention and nutrition advice, and seeking support for emotional and practical challenges. Working as a partner with your healthcare team gives you the best chance for long-term control of chronic GVHD and a better quality of life.
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.
The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: January 23, 2026.
