Health Info #8

Graft-versus-Host Disease (GVHD)
GVHD is a common complication following an allogeneic stem cell transplant. Twenty to fifty percent of patients undergoing a stem cell transplant with a related HLA-matched donor develop GVHD. The incidence is higher among older patients and those transplanted with stem cells from an unrelated donor or HLA mismatched donor.

GVHD is triggered by cells called T-cells. T-cells are a type of white blood cell that can recognize which cells belong in the individual's body,and which cells do not. When a donor's T-cells are transplanted into a patient, they perceive the patient's organs and tissues as foreign cells, and orchestrate an immune system attack to destroy them.

GVHD is often discusses as if it were a single disease. It is, in fact, two diseases: acute GVHD and chronic GVHD. Patients may develop one, both or neither. Acute and chronic GVHD differ in their symptoms, clinical signs and time of onset.

Acute GVHD
Patients who develop acute GVHD usually do so during the first three months after transplant. The earliest sign is often a faint rash on the patient's chest or back. A skin rash may also appear on the patient's hands and feet. The rash may spread to other parts of the body and develop into a general redness, similar to a sunburn, with peeling or blistering skin.

Acute GVHD can also affect the stomach and intestines causing cramping, nausea and watery or bloody diarrhea. Jaundice may indicate that acute GVHD has affected the liver.

Physicians grade the severity of acute GVHD according to the number of organs involved and the degree to which they're affected. Acute GVHD may be mild, moderate or sever or life-threatening.

Prevention and Treatment of Acute GVHD
To reduce the risk of developing acute GVHD, patients are typically given a combo of cyclosporine and methotrexate, tacrolimus and methotrexate or cyclospring and mycophenolate mofetil.

Stages of acute GVHD
Stage 1 (mild); a skin rash over less than 25% of the body.
Stage2 (moderate): a skin rash over more than 25% of the body accompanied by mild liver, stomach and intestinal disorders.
Stage 3 (severe): redness of the skin, similar to a sunburn and moderate liver, stomach and intestinal problems.
Stage 4 (live-threatening): blistering, peeling skin and severe liver, stomach and intestinal problems.

Chronic GVHD
Chronic GVHD develops during or after the third month post-transplant. Patients with chronic GVHD usually experience skin problems that may include a dry itching rash, a change in skin color, and tautness or tightening of the skin. Liver abnormalities, dry or burning eyes, dry mouth, mouth sores, infections and stomach irritations are also common symptoms of chronic GVHD

Less frequently, patients experience skin scarring, partial hair loss, or premature graying of the hair. Others develop severe liver problems, vision difficulties, heartburn, stomach pain, difficutly swallowing, weight loss or breathing difficulties. Lung problems are a common complication of chronic GVHD. These can be serious and require prompt treatment.

patients who have had acute GVHD have the greatest risk of developing chronic GVHD. Older patients, those transplanted with stem cells from an unrelated or HLA mismatched donor, and those transplanted with stem cells that were collected from the bloodstream rather than with bone marrow may also have a greater risk of developing chronic GVHD.

Symptoms/side effects of chronic GVHD
Most common- rash, itching, general redness of skin, dark spots, tautness of skin, jaundice, abnormal liver tests, dry,burning eyes, dryness or sores in the mouth, burning sensation when eating acidic food, bacterial infection.
Less common- skin scarring, partial hair loss, premature graying, severe liver disease, vision impairment, heartburn, stomach pain, difficulty swallowing, weight loss, contractures, difficulty breathing, bronchitis, pneumonia.

Health Info #7

Preparative Regimen
The preparative regimen (also called the conditioning regimen) is the high-dose chemo and/or radiation administered to the patient during the week preceding their transplant. The preparatie regimen has 2 objectives: to destroy the patient's disease, and to suppress the patient's immune system so that the donor stem cells can engraft and begin producing healthy blood cells. Depending on the disease being treated, the preperative regimen may consist of one or more chemo drugs, or a combination of chemo and total body irradiation (TBI).

High-Dose Chemotherapy
Most preparative regimens include high-dose combination chemo. The chemo drugs are administered intravenously. If the chemo drug busulfan is part of the preparative regimen, it may be administered IV or taken in pill form by mouth. The exact combination and dosage of chemo drugs and radiation used in the preparative regimen varies according to the disease being treated and the preferred treatment plan of the transplant facility. Since researchers are constantly investigating promising new drug combinations and dosages, two tranplant centers may use different preparative regimens to treat patients who have the same disease.

Side Effects
HIgh-dose chemotherapy and TBI are toxic to normal tissues and organs, as well as diseased cells. Nausea, vomiting, diarrhea, mouth sores and temporary hair loss almost always occur to varying degrees regardless of which preparative regimen is used. Sever or long-term damage to organs and tissues occurs less frequently.

Nausea, Vomiting and Diarrhea
Nausea and vomiting are common following all preparative regimens, but can usually be controlled with medications. Drugs called antiemetics are used to treat nausea (emesis means vomiting thus antiemetics are drugs that prevent vomiting.

The feeling of nausea is controlled by the brain, not by the stomach. Many antiemetics act on the central nervous system to counteract this side effect. Antiemetics can cause additional side effects such as anxiety, drowsiness and restlessness. Occasionally, muscle tightness, uncontrolled eye movement and shakiness can occure. These drugs reactions can be frightening, but are usually less serious than they appear. Lowering the dosage of the antiemetic, or administering an antihistamine usually reduces or eliminates these side affects.
Diarrhea following the preparative regimen is also common. Anti-diarrhea drugs sedate the nerves in the gastrointestinal area, slowing down muscle contractions and the diarrhea.

Mouth, Throat, Skin and Hair
High-dose chemotherapy and radiation target rapidly dividing cancer cells. However, some normal cells such as those that line the mouth, throat and gut, as well as hair and skin cells, also divide rapidly. These cells can be temporarily damaged by high-dose chemo.
Mouth sores (mucasitis) and throat discomfort (stomatitis) typically appear four to eight days following the preparative regimen. Topical anesthetics or narcotis given IV such as morphine, are used to relieve this discomfort. Frequent brushing of the teeth and gums with a soft brush or sph9onge and rinsing with a solution of saline can be soothing and help prevent mouth infections.
Mucositis often makes eating difficult or impossible. Patients may be fed through IV until the discomfort subsides. IV feeding is also used if the stomach is unable to absorb sufficient nutrients (malabsorptions) as a result of temporary irratation cause by the preparative regimen. Antacid medications may be given to counteract stomach irritation.

Temporary hair loss (alopecia) always occurs following the preparative regimen. Hair loss changes a patient's appearance and for some can be very distressing. Some patients prefer to shave their heads or cut their hair very short before hair loss begins. Hair normally gows backr within three to six months following the transplant. Sometimes the amount of curl or thickness of the new hair will differ from the patient's hair pre-transplant. In rare cases, alopecia may be permanent.

Skin rash is common following preparative regimens that include TBI, busulfan, etopside, carmustin or thiotepa. At some centers showers are recommended on hour and six hours after infusion of thiotepa to reduce the likelihood of developing a rash.
Less often hyperpigmentation- dark spots on the skin- occurs. These usually fade over a period of one to two months.

Bladder Irritation
Bladder irritation, sometimes evidenced by bloody or painful urination, can occur following the preparative reigmen, particularly those that include cyclophosphamide or ifosfamide. Increasing the rates of IV fluids, using a Foley catheter to irrigate the bladder and administering a drug called Mesna are techniques commonly used to prevent or treat this problem.

Liver, lungs and Heart.
Temporary organ damage can occur following high-dose chemo. It is usually both mild and completely reversible.
Liver blood test abnormalities occur in 50 percent of patients following the preparative regimen, but only a small fraction will develop actual liver damage. Patients may experience jaudince (yellowing of the skin), significant weight gain due to fluid retention, and abnormal blood levels of liver enzymes and bilirubin (a pigment produced during the break-up of red blood cells). Resting the liver and avoiding medications that aggravate the condition are the usual treatments until the liver heals itself.

Breathing irregularities can also occur following the preparative regimen. Ten to twenty percent of patients develop non-infectious pneumonia during the first four weeks post-transplant. In most cases, injury to the lungs is mild and temporary, but some patients do experience long-term breathing problems.

Mild, temporary heartbeat irregularities (arrhythmia) or rapid heartbeat can occur following the preparative regimen, particularly those that include clyclophosphamide or carmustine. Severe or long-term heart problems are very rare.

Confusion
Confusion or altered thinking are occasional, temporary side effects of the preparative regimen, or of drugs used to control other side effects. Confusion and altered thinking can be frightening both to the patient and to loved ones who observe it. It helps to remember that these problems are temporary and reversible, and can often be managed by changing the dosage or type of drugs the patient is receiving.

Muscle Spasms and Cramping
Muscle spasms are a common problem post-transplant. They are sometimes caused by an imbalance in electrolytes- minerals found in the body such as potassium, magnesium and calcium. These minerals must be maintained at certain levels to prevent organ malfunction. Muscle spasms can often be resolved by taking potassium, calcium, magnesium or phosphate supplements orally. Ask your doctor to prescribe the supplement, since not all sources of these minerals are absorbed equally well by the body. If there is no electrolyte imbalance, vitamin E or quinine in pill form sometimes resolves or reduces the problem.

Reproductive Organs
Damage to reproductive organs from high dose chemo is common, and usually results in permanent infertility. Patient age, gender, stage of sexual maturity, and dosage of chemo all affect the likelihood of becoming infertile post-transplant. In addition, women often experience premature menopause.

Other Long-Term Side Effects
Premature cataracts occur in approximately 20 percent of patients who undergo TBI. Cataracts may also occur following treatment with high-dose busulfan. Cataracts can be surgically removed, usually in an outpatient setting.

Some patients experience numbness and tingling in their hands and feet, due to nerve damage caused by the preparative regimen and prior chemo. The damage is usually permmanent. However, in a few patients there has been slow re-growth of nerve tissue that eventually reduces numbness and tingling. The problem is seldom resolved completely.

Mild to moderate learning disabilities may occur in children who've had a stem cell transplant, especially if the preperative therapy includes TBI. Younger children often experience delayed growth as well. Hormone therapy may be recommended to promote growth if this problem occurs.

Children transplanted before the age of five may also experience significant dental problems such as loose teeth, tooth loss, dry mouth and inability to wear braces. It is important that they be followed by a dentist who is experienced in treating child who've undergone high-dose chemo and/or TBI.