Allogeneic (donor) bone marrow and stem cell transplants are used to treat blood cancers such as leukemia and lymphoma. A bone marrow transplant is a type of stem cell transplant in which the cells come from bone marrow. In a stem cell transplant, the cells can also come from another’s blood or blood from a baby’s umbilical cord, according to the American Cancer Society. (2) In either case, the goal of the transplant is to replace your bone marrow with healthy stem cells to treat the cancer. “We would do a lot more transplants, but this immune system attack on the healthy tissue (GVHD) is a major obstacle that can offset some of that benefit,” says John Levine, MD, a hematologist-oncologist at Mount Sinai Hospital in New York City. “Otherwise, we would be using stem cell transplants even more routinely than we do now.” (3) The symptoms of GVHD can be mild, moderate, severe, or life threatening. (1) Acute GVHD usually develops in the weeks or months after a transplant, but it can also develop later. (4) The most common symptoms, which tend to appear and get worse over a matter of days, are a red skin rash, diarrhea, vomiting, and abnormal liver function tests. If symptoms occur 3 months or more after the transplant, it’s called late acute GVHD. Up to 50 percent of patients receiving a stem cell transplant from a sibling develop GVHD. That rate is typically even higher with unmatched donors. (1) Chronic GVHD typically develops within 1 year of a transplant. It can affect up to 80 percent of stem cell transplant recipients. (1) Almost any organ or tissue can be involved in chronic GVHD, but common symptoms include skin rash and thickening; muscle and joint stiffness; dry eyes and dry mouth; weight loss; and difficulty breathing. Chronic GVHD can also cause many other symptoms that often develop slowly, over weeks to months. According to Cleveland Clinic, after an allogeneic stem cell transplant, it’s possible to develop one or both forms of GVHD — or neither. (5) Because these markers are inherited, recipients have a 25 percent chance of being well matched with a sibling. But 70 percent of people who need a stem cell transplant don’t have a fully matched donor in their family. (6) The greatest risk factor for acute GVHD is how well the recipient’s and donor’s HLA match. The more mismatched, the greater the risk. Recipients are more likely to be well matched with someone of a similar ancestry or ethnic background. (7) Other risk factors include being an older patient, grafting with growth factor–mobilized blood cells (peripheral blood), and having a female donor if the recipient is male. “Blood cancer patients also tend to undergo chemotherapy, with or without radiation, before a bone marrow or stem cell transplant, and a higher intensity of therapy can increase the risk for GVHD,” says Doris Ponce, MD, an associate professor of medicine and the program director of GVHD at Memorial Sloan Kettering Cancer Center in New York City. (8) With chronic GVHD, the greatest risk factor is having already experienced acute GVHD. Other risk factors, as with acute GVHD, are a greater HLA mismatch and an older transplant recipient. (5)
Symptoms of Acute GVHD
Acute GVHD can affect the skin, gastrointestinal (GI) tract, and liver, according to the Leukemia & Lymphoma Society (LLS). (9) Symptoms can include:
Skin rash with burning and redness on the palms, soles of the feet, trunk, or other extremities; skin may blister or flake off in severe casesNausea, vomiting, abdominal cramping, and diarrheaYellowing of the skin or eyes (jaundice), along with abnormal blood test results (signs of liver problems)
Symptoms of Chronic GVHD
Chronic GVHD can involve one organ or several. (5, 9) Skin problems:
Dry, itchy skinSkin rashSkin thickening and tighteningIntolerance to temperature changes (due to damaged sweat glands)Change in skin color
Liver problems:
Abdominal swellingYellowing (jaundice) of the skin or eyesAbnormal blood test results
Nail and hair problems:
Changes in nail textureNail lossHair loss on scalp or bodyPremature gray hair
Eye problems:
Dry eyesVision changes
Oral problems:
Dry mouthPain or sensitivity to spicy foodsWhite patches inside the mouth
Lung problems:
Shortness of breathChronic coughWheezingChanges seen on a chest X-ray
GI problems:
Weight lossDifficulty or pain when swallowingLoss of appetiteStomach painNauseaVomitingDiarrhea
Nerve, muscle, and joint problems:
Muscle weaknessMuscle painFatigueJoint stiffness that makes it difficult to extend the fingers, wrists, elbows, knees, or ankles
Genital problems: Female:
Vaginal ulcers and scarringNarrowing of the vaginaVaginal dryness, itching, and painPainful intercourse
Male:
Penis irritationItching and scarring on the penis or scrotum
“It can sometimes be difficult to distinguish between acute and chronic GVHD. It’s always a good idea to review symptoms with the bone marrow transplant team, because sometimes the signs and symptoms can be subtle,” says Shernan Holtan, MD, an associate professor of medicine in the division of hematology, oncology, and transplantation at the University of Minnesota Medical School in Minneapolis. (10) Your oncologist will perform a physical exam and check your lab results for changes. If there are any, your doctor will first try to determine if any symptoms you’ve developed may be due to other causes. “Sometimes, biopsies of affected tissue are done to see if there are any changes,” says Dr. Levine. In mild cases of chronic GVHD, the symptoms can seem vague or due to something else. It’s important to mention to your care team any new symptoms you experience, to rule out the possibility of GVHD. (3)
Acute GVHD Treatment
If you only have mild symptoms, treatment can be simple. “If only the skin is affected and this affection is limited, patients can use a steroid topical treatment like a cream or ointment,” says Dr. Ponce. If acute GVHD symptoms are more severe or affect more of your body, it’s first treated with corticosteroids to suppress the immune system. According to the LLS, these can include medications such as:
PrednisoneMethylprednisoloneDexamethasoneBeclomethasoneBudesonide (9)
If steroids don’t work, your doctor may prescribe another type of immune system–suppressing medication known as ruxolitinib. Otherwise, your doctor may choose to prescribe a different medication for off-label use, meaning the U.S. Food and Drug Administration hasn’t approved it for use with GVHD, but doctors sometimes prescribe it to treat the disease. (3)
Chronic GVHD Treatment
As with acute GVHD, mild cases of chronic GVHD that affect a single organ can be treated with local therapies, such as a steroid cream for the skin or steroid eye drops. If you have more severe symptoms, or more organs are affected, you may be treated with systemic corticosteroid medications, such as prednisone. If you don’t respond to steroid treatment, your doctor can prescribe another type of immunosuppressant, such as:
RuxolitinibBelumosudilIbrutinib (8)
It’s also possible to seek treatment through clinical trials, adds Holtan. (10) Researchers continue to look into other GVHD treatment options that can replace steroids. That’s because steroids suppress your immune system and can cause many side effects if you have to use them for long periods of time, making you more susceptible to infections and illnesses. (3) T cells, a type of white blood cell that develops from stem cells in bone marrow, are part of the immune system and can help fight cancer. Doctors may remove T cells from the donor graft or give medications to suppress the T cells, so they are less likely to attack your cells. (9) Then, starting three days after the transplant and continuing for several months, doctors tend to prescribe a regimen of three immunosuppressant drugs:
Cyclophosphamide, a chemotherapy drugTacrolimusMycophenolate mofetil
“The idea is that you give nothing to prevent GVHD for the first three days, and you allow the donor cells to react to the patient. Then, when those cells divide, that makes them susceptible to the chemotherapy,” says Levine. “This approach tends to eliminate a lot of the cells that are getting geared up to go on a ‘killing spree,’ while preserving the regulatory side of the immune system.” (2) Together, all three drugs work to help lower your GVHD risk. The majority of people with GVHD, though, will survive. While your symptoms can be treated with medications, they may not go away completely. “Most of the treatments can result in some decrease in the symptom burden, but the treatments currently available don’t result in a complete response for most patients,” explains Levine. (2) Keep in mind, even if medications don’t eliminate your symptoms altogether, “Doctors are hoping to improve organ function, improve quality of life, and help the symptoms resolve to the greatest extent possible using medications with the fewest possible side effects,” says Holtan. “Overall, this is a very nuanced issue that requires careful discussion with your transplant physician, as the prognosis may vary widely from patient to patient.” (10) Be the Match This global organization connects bone marrow transplant recipients with donors. They can help you find a transplant center, prepare for the transplant, and learn what comes after a transplant. They offer peer support, one-on-one support, group support, information on financial help, and more. Leukemia & Lymphoma Society This nonprofit offers personalized disease and treatment information for people with blood cancer. They also provide information on financial support, such as copay assistance and travel assistance, and emotional support, such as peer support services, support groups, and online chats. BMT InfoNet This free resource connects volunteer caregivers of transplant and T-cell recipients with people who are preparing for the same treatment. They can provide you with nonmedical information and emotional support, offer tips for coping with household and job responsibilities, and more. Memorial Sloan Kettering Cancer Center Ponce suggests checking out the organization’s informational resources, such as recommended foods and drinks during cancer and GVHD clinical trials.
