A BMT is a potentially life-saving procedure, but with it comes the possibility of complications, some very serious and even life threatening. These complications can come quickly or later on and may persist for lengthy periods. Please do not delay in reporting symptoms to any member of the transplant team so we can treat you as soon as possible.
Graft Versus Host Disease (GVHD)
Except in the case of identical twins, there is some degree of incompatibility among all donors and recipients, even if they have six matching HLA antigens, so GVHD is a common complication following allogeneic BMT. The disease can range from mild to life-threatening, with short-term or long-term symptoms.
GVHD occurs when T-cells from the immune system of the donor recognize the proteins (antigens) on your cells as foreign. While GVHD may produce a beneficial antitumor effect, too much can cause severe problems, even death.
The incidence and severity of GVHD varies, depending upon the degree and types of differences between the donor and recipient:
Incidence of GVHD is highest among older patients and those transplanted from an unrelated donor or a mismatched donor.
GVHD can be acute or chronic. Patients may experience none, one or both types. Acute GVHD occurs within the first 100 days or so following allogeneic BMT, and chronic GVHD occurs after the first 100 days. Day 100 should be considered merely a guideline, however.
The first sign of acute GVHD is usually a mild skin rash. This may change into a sunburn-like redness. In more serious cases, skin may blister or peel. Acute GVHD can also affect the gastrointestinal tract and liver. Some combination of nausea, cramping, bloody or watery diarrhea and jaundice, a yellowing of the skin and eyes, may result.
Patients who have had acute GVHD are at greatest risk for developing chronic GVHD. However, a patient who has not had acute GVHD can still have chronic GVHD, which develops three or more months after a BMT. Skin problems, including rashes, itching, changes in skin color, lesions and tautness are typical.
Other common symptoms are liver abnormalities and infections. Chronic GVHD can attack glands, leading to dry or burning eyes, dry or burning mouth and mouth sores. Good oral hygiene is crucial to minimize infections.
Gastrointestinal irritations can make it difficult to properly absorb nutrients and lead to difficulty swallowing, heartburn, stomach pain and weight loss. At times, chronic GVHD causes skin scarring, premature graying of hair, hair loss, vision problems, liver injury and, occasionally, a tightening of the tendons in joints that can make arm and leg movement difficult.
Symptoms can range from mild to serious. They may occur alone or together. In severe cases, permanent disability or death may occur, although this does not happen frequently. The body’s immune system is weakened from chronic GVHD and immunosuppressive drugs. Because chronic GVHD also weakens barriers to infection such as skin and mucous membranes, infection is the leading cause of death from chronic GVHD.
Prior to your BMT, you will receive drugs to prevent infection and GVHD. It is imperative that you practice good hygiene throughout the transplant process.
The most common agents used to prevent GVHD are cyclosporine (CsA), tacrolimus (FK-506/Prograf), Methotrexate and steroids. Some form of prevention is always started before allogeneic BMT. It is critical that you take your anti-GVHD medications and not stop taking them without notifying your doctor, nurse practitioner or physician assistant.
Coping with GVHD can be very challenging for patients and their families. You may be angry that you must deal with this illness on top of everything else. Drugs you are taking may exaggerate mood swings, depression and anxiety. Please try to keep in mind that GVHD’s manifestations are temporary. The members of the transplant team are here to help you cope.
For some patients, symptoms such as skin sensitivity, eye irritation and gastrointestinal and liver problems do persist long term. Fortunately, most patients recover without significant long-term side effects. Researchers, including those at RPCI, continue to investigate ways to reduce the complications of this difficult disease.
Veno-occlusive Disease (VOD)
Your liver is a complex organ that performs many essential functions not duplicated by other organs in your body. If the blood vessels that transport blood through your liver become obstructed (blocked) or if your liver is damaged, it cannot properly rid your body of toxins, drugs and other waste products. If the flow of bile from your liver becomes obstructed, excess levels of bilirubin, cholesterol and other chemicals will build up in your body, interfering with the function of the liver and other organs.
Veno-occlusive disease is a potentially serious liver problem caused by the high doses of chemotherapy and/or radiation you receive before your BMT. In patients with VOD, the blood vessels that carry blood through the liver become swollen and obstructed. This impairs the ability of the liver to remove waste products from the bloodstream. Pressure and fluid build up in the liver, causing liver swelling and tenderness. The kidneys may retain excess water and salt, causing fluid to build up in the body. Swelling of the legs, arms and abdomen may occur.
In severe cases of VOD, fluid builds up and leaks into the abdominal cavity and may put pressure on the lungs and impair breathing. Toxins that the liver does not remove from the body may affect how the brain functions. Confusion may result. Symptoms of VOD – jaundice, an enlarged liver, pain or tenderness in the area of the liver, rapid weight gain, swelling and accumulation of fluid in the abdomen – are usually seen one to four weeks after the start of chemotherapy and/or radiation. VOD can be difficult to diagnose because its symptoms are also symptoms of other liver disorders.
When VOD is suspected, the medical team will attempt to prevent the more serious complications by:
Medications such as Heparin, Enoxaparin and Alteplase may be used to prevent and treat VOD.
Lung and Heart Complications
It is possible that high doses of chemotherapy, radiation, fluids or infections can affect your heart and lungs, decreasing their ability to function. For this reason, you will have tests before, during and after your transplant to monitor the condition of these organs.
You can play an important and active role in preventing lung complications. If you smoke, you must stop smoking prior to your admission for transplant. Smoking is not permitted while you are in the hospital, and resuming smoking after your transplant increases your risk of serious lung complications. Assistance and information is available to help you stop smoking.
While you are hospitalized, your health care providers will teach you activities to help you maintain healthy lung function. Your doctors and nurses will evaluate your lungs every day. If ordered by your physician, a respiratory therapist may provide treatment including aerosol medication, chest physiotherapy, oxygen and/or assisted ventilation. If you feel short of breath or uncomfortable at any time, tell your nurse or doctor.
Kidney and Bladder Complications
By producing urine, your kidneys help maintain the proper amount and characteristics of body fluids. They also process some drugs and remove other waste products from your body. Because of the intensity of the BMT process, it is not unusual to develop kidney problems. Although mild kidney problems are common, they are taken seriously and treated aggressively.
Many of the chemotherapy drugs and medications you will receive may be harmful to your kidneys and/or bladder. This is why your kidney function is closely monitored throughout treatment. Your weight will be taken every morning, blood samples will be taken frequently from your long-term IV catheter; intravenous and oral fluids will be measured carefully and recorded, and all urine, stool and emesis will be measured and recorded. This is called I & O (intake and output).
Some drugs affect the nerves in the bladder and may prevent you from completely emptying your bladder. Sometimes the volume of fluid that you receive intravenously to flush out the chemotherapy drugs is so large, that you will retain fluid. If this occurs, you may be given a diuretic to increase your urine output. If urine retention remains a problem, a Foley catheter (a small, soft tube) may be inserted through the urethra into the bladder, allowing the urine to flow freely into a collection bag. Urine retention usually subsides in a few days to weeks.
Occasionally, despite close monitoring and aggressive therapy, kidney failure that does not respond to medications such as diuretics may occur. In these cases, dialysis may be required to help the kidneys heal and to remove toxins that build up in the body. The need for dialysis may be temporary until kidney function returns. At times the need is permanent.
Conditioning regimens that include radiation can cause complications of the mouth and oral mucosa. Dry mucosal membranes can lead to decreased saliva production, poor oral hygiene and dental cavities. Careful oral hygiene is important, and must be continued after discharge. Brush your teeth at least three times a day with a soft toothbrush, floss and visit your dentist regularly.
Pain, burning, irritation and loss of taste are common complaints. Inadequate nutrition can cause weight loss, oral infections and dental cavities. Try a soft, bland diet and liquid nutritional supplements if necessary. Use artificial saliva and sugarless hard candy, gum and mints to help with changes in taste and saliva production.
Radiation and steroid therapy may cause cataracts. Squinting and poor vision are common symptoms; other symptoms include dry eyes, a feeling of grittiness, burning, itching and sensitivity to light. Protective sunglasses and artificial tears can reduce discomfort. Good medical follow-up is needed and surgical intervention might be required if cataracts form.
Thyroid problems may result if radiation is included in your conditioning regimen. Report symptoms such as lethargy, sluggishness, depression, sleep disturbances, swelling, weight gain and sparse or thinning hair. Blood will be drawn to monitor your thyroid function. Medication to replace thyroid hormones may be needed.
Complications of Steroids
Avascular necrosis – the loss of blood supply to the bone, which causes bone tissue to die – is a frequent complication of using steroids to manage treatment side effects. The head of the femur (thigh bone) is usually affected, but the head of the humerus (arm bone) can also be involved. An early symptom is a dull aching or a pressure sensation within the hip that becomes worse by weight bearing or extremes of hip motion, so any hip or shoulder pain or discomfort, limited range of motion, or stiffness in the joint (contractures) should be reported to your doctor. Surgical intervention might be needed.
Steroid myopathy is a chronic, painless muscle wasting and weakness caused by steroids. It usually begins in the pelvic girdle and may cause difficulty climbing stairs or rising from a seated position. It can also affect the shoulder girdle, making it difficult to lift objects. Eliminating or decreasing the dose of steroids is the most effective way to treat steroid myopathy. Muscle strength usually returns over time, but in some cases, muscle degeneration prevents a full recovery.
As steroids are being tapered, you might have muscle aches, mood changes, lethargy, loss of appetite and skin changes.
Other side effects of long-term use of steroids include a Cushingoid appearance (moon face), collapsed vertebrae, osteoporosis and hypertension. The list below gives more information about possible symptoms and how to deal with them:
Infertility can be a devastating side effect of BMT, but not all patients undergoing a BMT will experience infertility. It is not the BMT itself, but the high-dose chemotherapy and/or radiation administered before the BMT that damages reproductive cells. Chemotherapy can damage or destroy ovarian or testicular cells from which egg and sperm evolve. Radiation causes similar problems and can also damage the uterine lining or fallopian tubes.
Chemotherapy or radiation induced infertility can be temporary or permanent and can occur at low doses or the higher doses given pre-BMT. Patients who have undergone standard chemotherapy or radiation therapy for their disease before considering a BMT may already be infertile.
Certain chemotherapy drugs and dosages are especially toxic to reproductive cells. Younger patients are generally less likely to develop permanent infertility from standard therapy, however, high-dose therapy and total body irradiation can produce more severe toxic effects to the reproductive organs. High-dose steroids, often used during or after BMT, can also contribute to fertility problems. Please let us know if you have concerns about fertility.
Lack of Engraftment
In rare circumstances, the transplanted marrow or stem cells (donor cells or even the recipient’s own cells) do not repopulate the recipient’s marrow; this is called lack of engraftment or graft failure. When this happens, patients are predisposed to infections and other complications. They may need transfusions of blood (RBCs) and platelets for support. Treatment also can include erythropoetin and neupogen injections. Sometimes graft failure is life-long, even life threatening. Again, this is a very rare complication. Your transplant team will discuss this with you if applicable.
Occasionally, a transplant does not achieve its goal, and the patient’s disease doesn’t go into remission or it comes back. Because everyone has hoped for a cure, it is natural that this outcome is devastating for the patient, his or her family and the transplant team.
Should this happen, unfortunately, options for cure are limited. Some treatments can still potentially cure the disease, although it is more difficult with recurrent disease and much less likely to happen.
New or novel therapies or phase 1 clinical trials (studies that are evaluating promising new treatments) may be used. Sometimes, after discussion with physicians and loved ones, a patient decides to stop aggressive therapy and receive palliative care or comfort measures. These are meant to support the patient and help optimize whatever time he or she may have left.
Sometimes, people who have had chemotherapy and/or radiation may develop a second, new type of cancer. Even though used initially to treat their cancer, these agents are known to have long-term effects on the body.
When your doctor makes the recommendation to use these treatments, it is because he or she believes that the risk of not treating the disease is worse than the risk of possible side effects that may occur in the future.
A secondary malignancy can occur anytime after chemotherapy and radiation, at any point in a patient’s life. The medical team sees post-transplant patients at least once a year for life to screen for this possible complication. Some of the most common secondary malignancies are acute myeloid leukemia, myelodysplastic syndromes, skin cancer and other solid tumors such as lung cancer. You should talk to your health care providers regarding your individual risk.
Sometimes a patient’s cancer proves to be resistant to all the therapies we have to offer, and no matter how hard the patient, family and transplant team try, occasionally the BMT does not work, or complications may arise that are insurmountable. Death always is a possibility, no matter who we are and where we are in life.
Having a potentially fatal illness, and undergoing high-dose chemotherapy and/or radiation only point out how fragile life is. At Roswell Park Cancer Institute, we believe that patients should discuss their end of life wishes with their family, loved ones and medical providers to make sure their wishes are honored. We encourage all people to talk about their wishes, even if they are not sick. Please speak to your transplant team about a Health Care Proxy, Advanced Directive and the use of Do Not Resuscitate orders.