What Is Graft-Versus-Host Disease?

Complication of Donated Bone Marrow and Stem Cell Transplants

Table of Contents
View All
Table of Contents

Graft-versus-host disease (GvHD) is a complication of a stem cell or bone marrow transplant in which cells from a donor view the tissues of the recipient as "foreign" and launch an immune attack. This can trigger an array of symptoms, ranging from mild to severe, based on which organs are attacked.

Doctors try to avoid GvHD by genetically "matching" donors to recipients, often by recruiting a sibling or other family member with a similar genetic makeup. If GvHD symptoms develop, doctors can prescribe steroidal and nonsteroidal immune-suppressants that can temper and eventually control the autoimmune-like assault.

Graft-versus-host disease skin symptoms
lolostock / iStock / Getty Images 

Types of Graft-Versus-Host Disease

Bone marrow or stem cell transplants are sometimes used in people with leukemia and lymphoma as well as certain solid tumor cancers and blood-related disorders. GvHD is a complication associated with allogeneic transplants (in which cells are donated) rather than autologous transplants (in which the donor and recipient are the same).

There are two main types of GvHD, differentiated by the timing of their occurrence and distinctive clinical features:

  • Acute GvHD, also known as classic acute GvHD, occurs within 100 days of a transplant and mainly affects the skin, gastrointestinal tract, and liver in 70%, 74%, and 44% of cases, respectively.
  • Chronic GvHD, also known as classic chronic GvHD, occurs 100 days or more after a transplant and tends to affect the skin, liver, mouth, gastrointestinal tract, lungs, eyes, nervous system, or genitourinary tract.

GvHD doesn't always present in a consistent manner. It can sometimes manifest with features of acute and chronic GvHD, which doctors refer to as "overlap syndrome." If acute symptoms develop after 100 days, the condition is often referred to as persistent, recurrent, late-onset acute GVHD.

GvHD is associated with an increased risk of death in allogeneic transplant recipients, particularly those with high-grade disease.

Graft-Versus-Host Disease Symptoms

The symptoms of GvHD can differ from person to person but tend to involve specific organ systems and disease patterns. Acute GvHD typically manifests with the rapid onset of cutaneous (skin) symptoms, followed by those affecting and gastrointestinal (GI) tract and liver.

With chronic GvHD, the affected organ systems tend to be more diverse. Even so, the symptoms tend to originate in the skin before moving on to the gut, liver, lungs, eyes, and other organs. Chronic GvHD is also characterized by the tightening and hardening of the skin and connective tissues, similar in appearance to systemic sclerosis (scleroderma).

GvHD Type Organ System Symptoms
Acute Skin Rash on the palms and soles as well as the ears and shoulders, sometimes spreading to the whole body and often accompanied by pain, burning, and itching
  Liver Severe fatigue
Pain the upper right abdomen
Abdominal swelling
Loss of appetite
Nausea and vomiting
Dark urine
Chalk-colored stools
  Gastrointestinal Greenish, watery diarrhea
Bloody stools
Nausea and vomiting
Abdominal cramps
Indigestion and heartburn
Loss of appetite
Mouth pain
Gum disease
  Others Fever
Bacterial or viral infections
Chronic Skin Rash that is raised, thick, and discolored accompanied by skin that is abnormally tight, dry, itchy, and peeling
  Liver Same as acute GvHD
  Gastrointestinal Same as acute GvHD but often with mouth sores, difficulty swallowing, and pain with swallowing
  Others Hair loss
Premature graying
Hard, brittle nails
Dry, burning eyes
Extreme light sensitivity
Shortness of breath
Persistent dry cough
Frequent chest infections
Muscle weakness and pains
Joint pain and stiffness
Loss of range of motion
Vaginal narrowing (stenosis)
Vaginal dryness
Urethra stricture in men
Loss of libido
Pain with intercourse

The symptoms of acute and chronic GvHD can range from mild to severe. The severity and recurrence of symptoms can help predict the likely outcome (prognosis) of GvHD as well as a person's life expectancy (as measured by the survival rate).

For instance, people who develop eye problems with chronic GvHD will almost invariable have a poorer prognosis than those who don't. Similarly, people who develop oral lichen planus, an inflammatory condition frequently seen in people with chronic GvHD, are at an increased risk of aggressive oral cancers and early death.


The causes of graft-versus-host disease are complex but, at its heart, GvHD is characterized by a mismatch between certain genes in the transplant donor and transplant recipient.

These genes, referred to as major histocompatibility complex (MHC), are responsible for encoding surface proteins on cells known as human leukocyte antigen (HLA). HLA, in turn, helps the body differentiate between cells that are "normal" and those that are "foreign."

Any cell considered foreign will trigger an immune response, releasing an army of white blood cells, called T-cells, that target and neutralize the perceived invader.

With allogeneic transplants, donor cells will sometimes fail to recognize the recipient's tissues as normal due to minute variations in the HLA structure. If this occurs, the donor cells can turn the body's defenses on itself, leading to the onset of GvHD.

To reduce the risk of GvHD, specialists known as hematologist-oncologists will turn to family members to be donors as they are more likely to be genetically matched.

If no matches are available, the doctors match unrelated donors to recipients based on HLA blood test results. But even with a genetic match, the risk of GvHD remains high.

Research suggests that between 40% and 50% of people receiving a transplant from an HLA-matched sibling will develop acute GvHD, while 30% to 70% will develop chronic GvHD. The rate is even higher when an unrelated HLA-matched donor is involved.

Beyond HLA typing, there are other factors that can increase the risk of acute or chronic GvHD.

Acute GvHD Risk Factors
  • Older donor or recipient age

  • Being white

  • A female donor with a previous pregnancy

  • Having undergone total body irradiation (a method used to prevent the body from rejecting the transplanted cells)

Chronic GvHD Risk Factors
  • Older recipient age

  • Having had acute GvHD

  • Pairing a female donor with a male recipient

  • Having undergone a stem cell transplant with a mobilizing agent (used to encourage stem cells to migrate to bone marrow)

The type of transplant may also play a role in often surprising and contradictory ways.

According to a 2012 study in the New England Journal of Medicine, undergoing a bone marrow transplant reduces the risk of chronic GvHD compared to a peripheral-blood stem cell transplant (PBSCT). On the flip side, PBSCT is less likely to result in graft failure (in which a transplant fails to implant) compared to a bone marrow transplant.


It may seem reasonable to diagnose GvHD based on symptoms alone in an allogeneic transplant recipient. But there are actually strict criteria by which a diagnosis is made, in part to ensure that the symptoms are, in fact, GvHD and not some other condition.

According to guidelines issued by the National Institutes of Health (NIH), the diagnosis typically requires at least one clinical sign of GvHD paired with a biopsy or other test to confirm the characteristic features of the disease.

Examples of confirmatory tests include:

  • Organ-specific tests, such as pulmonary function tests (used to detect respiratory problems), bilirubin tests (used to detect liver dysfunction), and Schirmer tests (used to determine if a tear duct is producing tears)
  • Imaging tests, such as computed tomography (CT) scan with barium contrast to detect abnormalities in the gastrointestinal tract
  • Tissue biopsy, in which samples of skin, liver, gastrointestinal tract, mouth, lung, or genitals are taken to detect structural changes to tissues (such as sclerosis) under the microscope

The doctor would also take into account the timing of the symptoms and perform a differential diagnosis to exclude all other possible causes for the symptoms.

The NIH allows for some leeway in the diagnosis of acute GvHD if a classic rash, abdominal cramps with diarrhea, and increased bilirubin levels occur within the first 100 days of a transplant. In such cases, symptoms alone are enough to render a diagnosis.

The NIH also allows for leeway in the diagnosis of chronic GvHD based on whether the symptoms are "diagnostic" or "distinctive." Diagnostic symptoms are those regarded as defining features and do not require any form of confirmatory testing. Distinctive symptoms are those that are only suggestive of chronic GvHD and, therefore, must be supported by confirmatory testing.

Diagnostic vs. Distinctive Symptoms of Chronic GvHD
Organ System Diagnostic Distinctive
Skin Sclerosis Skin discoloration
  Lichen planus-like lesions  
Nails None Nail splitting and loss
Hair None New scalp hair loss
Mouth Lichen planus-like oral lesions Mouth ulcers
Eyes None Dry, gritty, or painful eyes
Genitals Lichen planus-like lesions Genital ulcers
  Vaginal scarring Vaginal fissures
Gastrointestinal Esophageal stricture None
  Esophageal webbing  
Liver None None
Lungs  Bronchiectasis diagnosed with a biopsy Bronchiectasis diagnosed by other means
Muscles/joints Fasciitis (inflammation of the fascia) Myositis (muscle inflammation)
  Joint stiffness  


Once GvHD has been diagnosed, the doctor will grade the condition to characterize its severity, direct the appropriate course of treatment, and offer a prognosis.

Acute GvHD

There are several classifications systems used to grade acute GvHD, but among the most popular is the International Bone Marrow Transplant Registry (IBMTR) grading system.

The IBMTR system grades the severity of acute GvHD based on the degree of involvement of the skin, liver, and gastrointestinal tract. The system is graded from A through D, with A being the mildest form and D being the most severe.

IBMTR Severity Index for Acute GvHD
A Mild disease Skin involvement alone (with a rash covering more than 25% of the body) with no liver or gastrointestinal involvement
B Moderate disease Skin involvement (with rash covering over 50% of the body) with mild to moderate liver or gastrointestinal symptoms
C Severe disease Widespread skin inflammation (erythroderma) covering more than 90% of the body with mild to severe involvement of either the liver or gastrointestinal tract
D Life-threatening disease The severe involvement of either the skin (erythroderma with bullous lesions), liver (bilirubin levels over 15 mg/dL), or gastrointestinal tract (over 2 liters of diarrhea per day with or without severe abdominal pain), or any combination of the above

Chronic GvHD

The grading system of chronic GvHD is slightly different. The system used by the NIH assigns a score ranging from 0 (for no symptoms) to 3 (for severe symptoms) for each of nine different organ systems: the skin, mouth, liver, upper GI tract, lower GI tract, esophagus, lungs, eyes, and joints.

These scores are then used individually, rather than cumulatively, to grade chronic GvHD as either mild, moderate, or severe. Mild GvHD is often referred to as low-grade disease, while moderate to severe GvHD are considered moderate- and high-grade disease, respectively.

NIH Severity Scoring for Chronic GvHD
Mild disease There is one or more organ sites with a score of 1
Moderate disease There are three or more organ sites with a score of 1, or
  There is at least one organ site with a score of 2, or
  The lung score of 1
Severe disease There is at least one organ site with a score of 3, or
  The lung score is either 2 or 3

Differential Diagnoses

Although some symptoms of GvHD are "classic," many others are non-specific and may have nothing with GvHD. To this end, doctors will explore other explanations for the symptoms to ensure the correct diagnosis. These may include:


GvHD is characterized by an inappropriate response of the immune system. As such, both acute GvHD and chronic GvHD are managed by reining in the immune system with immunosuppressant drugs. There are several types used in the treatment of GvHD.


Corticosteroid drugs (a.k.a. steroids) are the cornerstone of treatment for both acute and chronic GvHD. Corticosteroids temper the immune system by mimicking a hormone called cortisol that helps regulate the immune response (including the activation of T-cells).

Mild cutaneous GvHD may only require a topical steroid to control skin symptoms. Options range from low-potency 1% hydrocortisone cream to high-potency 0.05% clobetasol propionate ointment. PUVA phototherapy and Protopic (topical tacrolimus) may be added to the treatment plan for moderate to severe cases.

Severe symptoms in people with GvHD are typically treated with intravenous corticosteroids like prednisone and methylprednisone.

While effective at quickly relieving acute GvHD symptoms, high-dose steroids can increase the risk of bacterial, fungal, and viral infections as well as the likelihood of cancer recurrence.

To avoid this, the steroid dose is gradually tapered over the course of months once the condition has been brought under control. Some people may require no further treatment. Others may require long-term topical, oral, or IV steroids to manage their condition, either alone or in combination with other therapies.

Other Immunosuppressants

In addition to steroids, there is an increasing number of nonsteroidal immune suppressants used to control GvHD, especially when the long-term harms of corticosteroid use outweigh the benefits. These include:

  • Jakafi (ruxolitinib): FDA approved in 2019, Jakafi can be beneficial in patients who have not responded as well to steroids.
  • CellCept (mycophenolate mofetil): An immunosuppressant used to prevent heart, liver, or kidney transplant rejection
  • Enbrel (etanercept): A drug commonly used to treat autoimmune diseases
  • Methotrexate: A commonly prescribed immunosuppressant drug used to treat certain cancers and autoimmune diseases
  • Nipent (pentostatin): An anticancer drug that can be used to treat severe, treatment-resistance GvHD
  • Ontak (denileukin diftitox): Another anticancer drug that is sometimes used when corticosteroid drug resistance develops
  • Prograf (tacrolimus): An oral immunosuppressant related to Protopic
  • Rapamune (sirolimus): An immunosuppressant commonly used to prevent kidney transplant rejection
  • Remicade (infliximab): A popular immunosuppressant used to treat autoimmune disorders
  • Thalomid (thalidomide): An anticancer drug that has immunomodulating effects
  • Thymoglobulin (anti-thymocyte globulin): A T-cell reducing agent
  • Zenapax (daclizumab): An immunosuppressive monoclonal antibody

Even if symptoms aren't entirely resolved, there are some benefits to having mild GvHD. Among other things, the abnormal activation of T-cells can kill any remaining cancer cells—referred to as the graft-versus-tumor (GVT) effect—while reducing the risk of cancer recurrence.

Maintaining the balance between GVT and GvHD can be tricky but, with consistent care from a skilled oncologist, the right therapy can be found and fine-tuned to achieve control.


Between 40% and 60% of people with acute GvHD will respond to corticosteroid therapy within four weeks. Failure to respond by an improvement of at least one grade is associated with a poor prognosis, translating to a six-month mortality rate of 45% to 65%. Those who fail to respond with grade 4 GvHD have closer to a 95% likelihood of death within six months.

Although people who respond to corticosteroids have far better outlooks, the overall five-year survival rate hovers around 50% (meaning that half of all people with GvHD will live for at least five years). Of those who do respond to corticosteroid therapy, anywhere from 20% to 25% will relapse.

Having acute GvHD is the predominant risk factor for the development of chronic GvHD and almost invariably leads to worse outcomes when it does.

Chronic GvHD is not only associated with debilitating illness in roughly a third of all cases but is also the leading cause of death non-relapse death, usually as the result of an infection.


There is no way to predict who will get GvHD, how well they will respond to treatment if they do, or whether or not they will relapse. The uncertainty can cause a great deal of stress, adding to the challenges that a transplant recipient already faces.

To better cope, you need to address symptoms of fatigue and weight loss that can complicate recovery as well as dealing with common skin and respiratory problems. Among the self-help tips:


Gentle exercise can improve joint flexibility and range of motion, increase lean muscle mass, and help overcome persistent fatigue. Incorporating gentle aerobics in your exercise plans, such a brisk walk, can improve respiratory function while stimulating the release of the "feel-good" hormones called endorphins.

Skin Care

Regular moisturizing is key to improving the tightness and dryness of the skin. Use an emollient-rich moisturizer without perfumes or fragrance, applied immediately after showering and throughout the day as needed.

Wear loose breathable fabrics like cotton to avoid heat build-up, which can trigger skin inflammation, and always wear sunscreen with a minimum SPF 15 when outdoors.


GvHD occurring in the gastrointestinal tract can cause significant diarrhea and weight loss. It often helps to embark on a BRAT diet (an acronym for bananas, rice, apple, and toast) to deal with acute diarrhea.

Follow with a low-fiber, high-energy diet (defined as 1.2 to 1.5 grams of protein per kilogram of body weight per day) to prevent symptom recurrence and reverse weight loss. It often helps to work with a dietitian to ensure you get the calories and nutrition needed to maintain optimal health.


GvHD can sometimes affect the genitals and libido of both women and men. Estrogen cream (used two to three times weekly) may be prescribed to help soften vaginal tissues, while vaginal dilators can be used on a regular basis to avoid or reduce vaginal stenosis.

Testosterone replacement therapy can often help improve libido in men. Medical treatment under the care of a urologist or reconstructive surgeon may be needed to treat severe urethral stricture or vaginal stenosis.

Stress Management

Stress can impact any illness, but, with chronic GvHD, it can compound breathing problems by increasing the respiratory rate in lungs that may already be compromised.

To compensate, a physical therapist can teach you breathing exercises (like diaphragmic breathing and pursed-lip breathing) that not only increase the respiratory volume but help reduce stress by slowing the respiratory and heart rate.

Other stress management techniques include meditation, progressive muscle relaxation (PMR), and guided imagery.

It is also important to seek support from friends, family members, and support groups to better deal with the challenges of living with a transplant, whether you have GvHD or not.

A Word From Verywell

As distressing as it may be to diagnosed with graft-versus-host disease, it is important to remember that GvHD is more common than people think and can even occur when a donor is the "perfect match." If symptoms develop, they can often be effectively controlled medications. While some people require lifelong treatment, a great many don't.

To better cope with treatment, remain linked to medical care and maintain a healthy lifestyle, including a proper diet, routine exercise, and the avoidance of infections. These may not only reduce the severity of GvHD symptoms but improve your overall quality of life.

26 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Majhail NS, Farnia SH, Carpenter PA, et al. Indications for autologous and allogeneic hematopoietic cell transplantation: Guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2015;21(11):1863-9. doi:10.1016/j.bbmt.2015.07.032

  2. Wolfe D, Lawitschka A. Chapter 44: Chronic graft-versus-host disease. In: The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies [Internet]. 7th edition.

  3. Cleveland Clinic. Graft versus host disease: An overview in bone marrow transplant.

  4. Pidala J, Vogelsang G, Martin P, et al. Overlap subtype of chronic graft-versus-host disease is associated with an adverse prognosis, functional impairment, and inferior patient-reported outcomes: a Chronic Graft-versus-Host Disease Consortium study. Haematologica. 2012;97(3):451-8. doi:10.3324/haematol.2011.055186

  5. Levine JE, Logan B, Wu J, et al. Graft-versus-host disease treatment: Predictors of survivalBiol Blood Marrow Transplant. 2010;16(12):1693-1699. doi:10.1016/j.bbmt.2010.05.019

  6. Zeiser R, Blazar BR. Acute graft-versus-host disease - biologic process, prevention, and therapy. N Engl J Med. 2017;377(22):2167-79. doi:10.1056/NEJMra1609337

  7. Martires KJ, Baird K, Steinberg SM, et al. Sclerotic-type chronic GVHD of the skin: clinical risk factors, laboratory markers, and burden of disease. Blood. 2011;118(15):4250-4257. doi:10.1182/blood-2011-04-350249

  8. Sun YC, Chai X, Inamoto Y, et al. Impact of ocular chronic graft-versus-host disease on quality of life. Biol Blood Marrow Transplant. 2015;21(9):1687-91. doi:10.1016/j.bbmt.2015.05.020

  9. Tsukada S, Itonaga H, Taguchi J, Miyoshi T, Hayashida S, Sato S, et al. Gingival squamous cell carcinoma diagnosed on the occasion of osteonecrosis of the jaw in a patient with chronic GVHD. Rinsho Ketsueki. 2019;60(1):22-7. 27. doi:10.11406/rinketsu.60.22

  10. Lazaryan A, Weisdorf DJ, Defor T, et al. Risk factors for acute and chronic graft-versus-host disease after allogeneic hematopoietic cell transplantation with umbilical cord blood and matched sibling donors. Biol Blood Marrow Transplant. 2016;22(1):134-40. doi:10.1016/j.bbmt.2015.09.008

  11. Flowers ME, Inamoto Y, Carpenter PA, et al. Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria. Blood. 2011;117(11):3214-9. doi:10.1182/blood-2010-08-302109

  12. Anasetti C, Logan BR, Lee SJ, et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. N Engl J Med. 2012;367(16):1487-96. doi:10.1056/NEJMoa1203517

  13. Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015;21(3):389-401.e1. doi:10.1016/j.bbmt.2014.12.001

  14. Lee SJ. Classification systems for chronic graft-versus-host disease. Blood. 2017;129(1):30-7. doi:10.1182/blood-2016-07-686642

  15. Choi SW, Levine JE, Ferrara JL. Pathogenesis and management of graft-versus-host disease. Immunol Allergy Clin North Am. 2010;30(1):75-101. doi:10.1016/j.iac.2009.10.001

  16. Dignan FL, Amrolia P, Clark A, et al. Diagnosis and management of chronic graft-versus-host disease. Br J Haematol. 2012;158(1):46-61. doi:10.1111/j.1365-2141.2012.09128.x

  17. American Cancer Society. Stem cell or bone marrow transplant side effects.

  18. Lee SJ, Nguyen TD, Onstad L, et al. Success of immunosuppressive treatments in patients with chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2018;24(3):555-62. doi:10.1016/j.bbmt.2017.10.042

  19. Falkenburg JHF, Jedema I. Graft versus tumor effects and why people relapse. Hematology Am Soc Hematol Educ Program. 2017;2017(1):693-698. doi:10.1182/asheducation-2017.1.693

  20. Murata M, Nakasone H, Kanda J, et al. Clinical factors predicting the response of acute graft-versus-host disease to corticosteroid therapy: An analysis from the GVHD working group of the Japan Society for Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2013;19(8):1183-9. doi:10.1016/j.bbmt.2013.05.003

  21. Cahn JY, Klein JP, Lee SJ, et al. Prospective evaluation of 2 acute graft-versus-host (GVHD) grading systems: a joint Société Française de Greffe de Moëlle et Thérapie Cellulaire (SFGM-TC), Dana Farber Cancer Institute (DFCI), and International Bone Marrow Transplant Registry (IBMTR) prospective studyBlood. 2005;106(4):1495-1500. doi:10.1182/blood-2004-11-4557

  22. Kato M, Kurata M, Kanda J, et al. Impact of graft-versus-host disease on relapse and survival after allogeneic stem cell transplantation for pediatric leukemia. Bone marrow Transplant. 2019 Jan;54(1):68-75. doi:10.1038/s41409-018-0221-6

  23. Fluza-Luces C, Gonzalez-Murillo A, Soares-Miranda L, et al. Effects of exercise interventions in graft-versus-host disease models. Cell transplant. 2013;22(12):2409-20. doi:10.3727/096368912X658746

  24. Cancer Research UK. Treatment for chronic GvHD.

  25. Bassim CW, Fassil H, Dobbin M, et al. Malnutrition in patients with chronic GVHD. Bone Marrow Transplant. 2014 Oct;49(10):1300-6. doi:10.1038/bmt.2014.145

  26. Noerskov KH, Schjødt I, Syrjala KL, Jarden M. Sexual function 1-year after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2016;51(6):833-40. doi:10.1038/bmt.2015.342

By James Myhre & Dennis Sifris, MD
Dennis Sifris, MD, is an HIV specialist and Medical Director of LifeSense Disease Management. James Myhre is an American journalist and HIV educator.