Late Effects, Late Complications

• Late effects are emerging phenomena
  
• Terminology
  
• Adrenal dysfunction, Cushing's syndrome
  
• Cognitive and psychological damage
  
• Diabetes
  
• Eyes
  
• Fatigue
  
• Graft-versus-host disease
  
• Growth impairment
  
• Hair loss
  
• Heart and vascular damage
  
• Kidney or bladder damage
  
• Liver damage
  
• Low blood counts
  
• Lung damage
  
• Lymphedema
  
• Mouth, teeth, and throat
  
• Numbness, tingling, dizziness, paralysis, deafness
  
• Pain
  
• Radiation fibrosis
  
• Recall sensitivity
  
• Second cancers
  
• Sexuality and fertility
  
• Shingles
  
• Shortness of breath
  
• Skeletal damage
  
• Skin
  
• Stomach or intestinal distress
  
• Surgical complications
  
• Swollen arms, legs, hands, feet
  
• Thyroid dysfunction
  

It's difficult to imagine that treatments strong enough to kill NHL would not have an effect on normal, healthy tissue, too. In many cases, these treatments do affect normal cells, but usually these side effects are temporary, disappearing within days or weeks. A few side effects of treatment, though, last far longer for some people, and some late effects do not emerge until years after treatment.

The majority of NHL survivors do not have long-term effects or complications after treatment, or at most they have just one or two lasting effects that may fade away to an inconvenience rather than a problem. A few people, however, have serious long-term effects. Differences among people and their reactions depend on what drugs were given, how they were given, how long they were given, at what dose, what other health problems coexist with cancer, what previous drugs were given, and so on.

At times, it's very hard to accept that NHL ' s effect on our lives may not end when our treatment ends. This may mean that the discussion that follows is one that you're not ready to read just yet. If you're feeling battered today, put this aside until you feel better, or ask a loved one to read it for you.

Despite our reluctance and fears, it's important for us to know at least a little about long-term effects, for they can be confused with a relapse or can of themselves be life threatening. Often, but not always, they can be addressed and corrected.

This article will detail what effects are known to follow certain treatments in some people, and what, if anything, can be done about them. In the summary, we'll discuss why long-term effects can be expected to be less pronounced with newer treatments becoming available. The transient side effects of treatment are discussed in the chapter on side effects.

Late effects are emerging phenomena

Until about twenty years ago, not enough people treated with chemotherapy and radiotherapy for lymphoma and other cancers survived to characterize the lingering problems that are related to treatment or disease. The earliest cancer cures were affected with surgery only, and only for early-stage cancers. The introduction of multi-agent chemotherapy and combined chemotherapy and radiotherapy has saved enough people to make the pattern of late effects at least more obvious, while not yet fully understood. This is particularly so for those who've survived the Hodgkin's lymphomas, childhood acute lymphoblastic leukemia, intermediate- and high-grade non-Hodgkin's lymphomas, and for young males who have survived testicular cancer.

In almost all cases, late effects are more profound for survivors of childhood NHL.

In some cases, combination treatments of chemotherapy and radiotherapy make long-term effects more pronounced.

Terminology

What distinguishes the side effects of treatment from delayed or late effects and complications? The somewhat arbitrary definitions are that side effects of treatment are those that occur within days or weeks of treatment; delayed effects occur within weeks or months of cancer treatment; late effects occur months or years after treatment. Some side effects drift into becoming delayed or late effects, such as unremitting diarrhea induced by abdominal irradiation. The medical community distinguishes between effects and complications by defining effects as expected, and complications as somewhat unexpected.

The following sections, listed alphabetically, discuss specific late effects and complications.

Adrenal dysfunction, Cushing's syndrome

Irradiating the kidney can affect the adrenal gland which sits atop the kidney, causing it to malfunction. If the adrenal gland produces too much hormone, Cushing's syndrome can result. If too little, an Addison's-like disorder can result.

Abrupt withdrawal of the drug prednisone can cause a temporary adrenal dysfunction that resembles Addison's disease. Prednisone is a manmade version of the corticosteroid hormone cortisol, normally produced by the adrenal gland. When we add the synthetic version to our body, the adrenal gland, in concert with other glands, senses this, and shuts down production of its own version of cortisol. When we stop taking the drug, the adrenal cannot immediately begin again to make its own. For this reason, if you are taking prednisone for an extended time, the dosage should be tapered to a stop, not stopped abruptly.

Conversely, using the drug prednisone to fight NHL or to control the after-effects of treatment can produce a "Cushingoid" syndrome that mimics overactive adrenal glands. This normally regresses when prednisone usage is stopped, but may result in temporary or permanent diabetes.

If you experience weight gain in the abdomen with thin arms and legs, weight loss, moon-face, increased thirst, hair loss, browning of the skin at joints, skin thickening or thinning, and if you are not taking prednisone, ask your doctor to do an ACTH stimulation of the pituitary gland, and dexamethasone suppression testing of the adrenal glands.

Adrenal dysfunction also can be linked to disease of the thyroid or pancreas (diabetes), or damage to brain organs such as the pituitary.

Cognitive and psychological damage

Many NHL survivors report that their memory, concentration, logic, and reasoning skills no longer seem as good as they once were. This is especially so among those who have had cranial irradiation, methotrexate administered to the spine, or the high-dose chemotherapy and total body irradiation that accompanies bone marrow or stem cell transplantation or rescue.

Specific problems mentioned are short-term memory loss, failed word retrieval, reduced math skills, confusing the spelling of words that sound similar (homonyms), moodiness, shortened attention span, and depression.

I have definitely suffered some loss of comprehension when I read. It appears to be permanent, but then I'm not dead yet, so you never know. I went right from six months of standard chemotherapy into chemotherapy to prepare me for a bone marrow transplant, and that may be why. I completely lose my vocabulary sometimes, too, as if the synapses get crossed or something.

My memory has also suffered. I used to rely on it for just about anything. Now I rely on my notes.

There are no known solutions yet for these problems, although interesting research is being done with hyperbaric oxygen treatments to reverse the effects of radiation on the blood supply to the brain.

Post-traumatic stress disorder, depression, and anxiety are recognized sequels to cancer's stress, and can be addressed by a professional experienced in handling the psychological issues of cancer survivorship.

Diabetes

Diabetes can arise temporarily or permanently following treatment with prednisone, which is a synthetic copy of the natural adrenal hormone hydrocortisone, or following radiotherapy of the abdomen or brain.

If you experience increased thirst, weight loss, increased episodes of fungal infection, changed eyesight, slow wound healing, increased urination, and mental confusion or faintness, ask your doctor to test you for diabetes.

Diabetes can arise secondarily as a result of adrenal disorders, and often will recede when the adrenal disorder has been corrected.

Eyes

Radiotherapy or steroid therapy can cause cataracts; radiotherapy can cause "dry eye." Cataracts can be repaired with surgery. Dry eye can be treated with eye drops or prescription drugs.

NHL survivors who remain immune-suppressed may experience a reactivation of cytomegalovirus or of varicella Zoster (herpes Zoster or shingles, about which more is said below), which can affect eyesight. These infections should be treated promptly with antiviral drugs.

Fatigue

The National Cancer Institute reports long-term fatigue as one of the most debilitating long-term symptoms associated with cancer treatment.

For far too long, many cancer survivors weren't believed when they reported fatigue that lasted for years following treatment. The opinion used to be that one should feel tired only while red blood cell counts remained in the abnormally low range.

Now, doctors are listening more carefully to what survivors are saying about fatigue. One study of survivors of the Hodgkin's lymphomas has shown that 37 percent of about four hundred people studied experienced fatigue for as long as nine years after treatment. A study of 125 survivors of bone marrow transplantation revealed that about half experienced chronic fatigue for ten or more years following transplant.

The remaining problem is that medicine often cannot tell us why long-term fatigue occurs or what to do about it, although fatigue seems to increase as the duration or intensity of treatment is increased. Treatments such as tamoxifen or interferon that are spread over a very long time period can cause long-term fatigue. Other causes of fatigue include difficulty breathing, cranial irradiation, damage to the heart, liver, or kidneys, chronic pain, or the worry that accompanies cancer.

A five-year transplant survivor describes her ongoing problem with fatigue:

I still experience a chronic state of exhaustion. I believe it's just something I have to learn to live with. It has taken a few years to accept it, but now I just plan more carefully. I know that everything I do "costs" energy, and I know that I'll need recovery time afterward. Here's an example:

I wanted to attend a play a friend was in, in my hometown two hours away, with a stop to visit my mother-in-law. I had not slept well the night before, and that little ( formerly only inconvenient) fact made all the difference. Even though my husband was doing the driving, by the time we arrived at my mother-in-law's, I could feel the internal shaking from fatigue. When I got up to change my dress for dinner and the play, sweat started pouring. I was nauseated, and visibly shaking. I thought if I could make it to the car, perhaps I could sleep at my friends' house and put dinner off for a little while. We got in the car, but before we had driven two blocks, my husband had to pull over so that I could vomit. We returned to my mother-in-law's, and I lay down with the room spinning. After a tea-and-toast meal and an hour's sleep, the symptoms stopped.

Currently, the only proposed solution for long-term fatigue not attributable to known causes such as low blood counts or organ damage is plenty of rest, good nutrition, a carefully balanced workload, and emotional support.

Graft-versus-host disease

The tendency for white blood cells from donor-transplanted bone marrow to attack the body tissues of the recipient causes painful and potentially fatal side effects known collectively as graft-versus-host disease (GVHD).

Some researchers have noted GVHD even following autologous marrow or stem cell rescue (that is, using one's own marrow) if immunosuppressive drugs are administered and then abruptly withdrawn.

At its worst, GVHD may attack skin, liver, or intestine, alone or in combination. Although GVHD may fade away after eight or ten years, many transplant survivors spend years on immunosuppressive drugs to control this phenomenon.

A certain amount of GVHD is desirable because it also confers a beneficial graft-versus-lymphoma effect that lowers the risk of relapse. Thus, doses of immunosuppressive drugs are carefully titrated to achieve a balance between life-saving immunosuppression and a small amount of graft-versus-lymphoma effect.

Growth impairment (short stature, precocious puberty)

Children who have had cranial irradiation, total body irradiation, or brain surgery involving the pituitary gland, may sustain damage to the pituitary and the hypothalamus, two brain organs that interact to control growth.

Growth hormone levels should be monitored, and supplemented if necessary, in childhood cancer survivors. Impaired growth can cause a host of physical problems such as very early adolescence, as well as a series of academic, behavioral, and health problems.

Hair loss (alopecia)

Radiotherapy to the head, armpits, or groin, or treatment with the chemotherapeutic agent busulfan, can result in permanent hair loss. Sometimes the loss is not evident until months later when the existing hair is shed from the follicle, and the hair does not regrow. This is more common following cranial irradiation, high doses of busulfan, or total body irradiation. It is also more common among females or among those suffering from graft-versus-host-disease after bone marrow transplantation.

There is no treatment yet for this disorder.

Heart and vascular damage

Heart and vascular damage can emerge years after treatment with no previous warning symptoms.

Chemotherapeutic agents known to cause cardiovascular damage are:

• Doxorubicin (adriamycin) can cause heart damage if given in high doses or for a long time. The risk of heart damage rises greatly at lifetime doses above 350 to 500 milligrams per square meter of body surface area.
• Vincristine (Oncovin) can damage veins.
• Ifosfamide is also suspected of causing cardiovascular damage.

Radiation to the chest can damage the heart or its pouch-like linings, the pericardium and endocardium, the valves, or can constrict nearby tissues, arteries, and veins, affecting heart function.

If you have any symptoms of heart disease, such as chest pain or tightness, swollen arms or legs, numbness in your arms or hands, difficulty breathing, unusual heart rhythms, or dizziness, see your doctor for an echocardiogram, a stress EKG, or MUGA testing. In some cases, medication or common surgeries can help alleviate heart disease. In extreme cases, a heart transplant may be recommended.

Kidney or bladder damage

Ifosfamide, the nitrosureas, methotrexate, cisplatin, or cyclophosphamide can cause urinary tract damage, although Mesna now is used to protect the bladder from ifosfamide and cyclophosphamide damage, and allopurinol is used to guard the kidneys from the toxins of dying tumors.

Sometimes kidney damage is transient, and sometimes kidney function can be improved or stabilized with dietary changes or dialysis, but sometimes it cannot. In extreme cases, a kidney transplant may be recommended.

Liver damage

Permanent liver damage following chemotherapy is rare, except for that associated with high-dose treatment used as part of bone marrow transplantation. Liver damage associated with graft-versus-host disease following donor marrow transplantation is well known.

Radiation of the entire liver is seldom used for NHL, although involved-field radiation of small parts of the liver may be done. This reduces the risk of liver failure, because the remaining healthy liver, unlike some other organs, is capable of regeneration to replace damaged tissue.

If you're tired, nauseated, or your skin seems yellow or suntanned, call your doctor. Blood tests can detect changes in liver function, and dietary changes or modification of medications and dosages may alleviate the problem. In extreme cases, a liver transplant may be recommended.

Low blood counts

Low or low-normal blood counts can persist for years after treatment, especially following marrow or stem cell transplantation or rescue, owing to the high doses of chemotherapy and radiation used in these procedures. Some drugs, such as fludarabine used for low-grade NHL, do not suppress blood counts greatly at the time they're given, but do suppress the marrow's ability to regenerate blood products over the long term.

Fatigue, infection, or clotting problems can result from low blood counts.

For those with low red blood cell counts, long-term injections of erythropoietin are used to force production of extra red cells if the marrow remains capable of producing red cells. (If it is not, administration of growth factors will not be useful.) Repeated whole blood or red cell transfusions are commonly done, too.

For those with low platelet counts, new drugs still in the testing stage called recombinant thrombopoietins may help produce new platelets if the marrow remains capable of producing platelets--if not, administration of growth factors will not be useful. Repeated transfusion of platelets is commonly done as well.

For those with low white blood cell counts, injections of granulocyte colony stimulating factor (GCSF) or granulocyte-macrophage colony stimulating factor (GM-CSF) are possible. As with red cells and platelets, injection of growth factors are successful only if the marrow remains capable of producing these cells.

Transfusion of white blood cells from a donor are not recommended for those who are not on immunosuppressive drugs, because white blood cells from a donor will attack the recipient's tissue, and white cells from the recipient will attack the donated cells.

Lung damage

Radiotherapy or the chemotherapeutic agents carmustine (BCNU), busulfan, cyclophosphamide, melphelan, bleomycin, or methotrexate can cause lung damage.

My lung condition resembled both sarcoidosis and NHL that had metastasized to the lung. My CT scans were sent to a specialist, and it was established that I had had an allergic reaction to the methotrexate given pretransplant, and the lung condition had been progressing in the year since. I was treated with prednisone for about three months, and full lung capacity was restored, although I have scarring and pain in my lungs as a result. (Nothing I can't live with!)

Radiation therapy administered to children targeted to the chest may limit the growth of chest structures, causing diminished lung capacity.

If you have chest pain, cough, or any difficulty breathing, or if you have odd swellings under your skin near the chest, stomach, or arms, report it to your doctor as soon as possible. It might be the first symptom of pulmonary damage caused by the treatments you received: symptoms of fibrous scarring in the lung or, rarely, of pneumothorax, which is air that escapes from the lung and settles elsewhere in the body.

Lymphedema

The swelling of body parts owing to lymphatic fluid that cannot move is called lymphedema, and can emerge as late as fifteen or more years after cancer treatment. The lymphatic ducts are delicate vessels that collect fluid squeezed from veins during normal metabolism and bring it back to the veins near the heart. When these vessels become damaged, lymphedema may occur.

The NHL survivor might confuse it with the fluid retention that signals heart, liver, or kidney failure.

If you had radiation therapy, or surgery that might have affected lymph nodes or lymphatic ducts such as removal of pelvic or armpit nodes, and if you were given instructions to follow to reduce the chance of lymphedema, it's very important to follow these instructions for years afterward. Lymphedema can interfere with blood flow and wound healing, and may interfere with the immune response against tumors.

An early sign of lymphedema is a slight impression remaining in the skin when a finger is pressed against it. A sign of more serious lymphedema is a deeper impression following pressure that takes up to thirty seconds to disappear. Symptoms of serious edema are limbs that swell to twice their normal size.

There are many ways to prevent lymphedema, from elevation of a limb to certain hygienic habits or avoiding sun exposure. Ask your doctor about instructions specific for your condition, call NCI at (800) 4-CANCER, or contact the Lymphedema Network.

Lymphedema can be treated with variable success with certain drugs, such as antibiotics and diuretics, but the best cure is prevention.

Mouth, teeth, and throat

Radiation therapy to the head or neck as well as chemotherapy cause many transient side effects, but the dry mouth that may continue long after treatment ends can cause serious problems with dental health, and scar tissue that forms in the throat following radiotherapy may interfere with swallowing or breathing.

If you have dry mouth, you will be at risk for dental problems because the infection-fighting ingredients of saliva are missing. Ask your doctor and dentist for instructions for daily care, such as frequent rinsing with salt water. See your dentist immediately for any redness or swelling in your mouth, or for cracked or discolored teeth, even if you have no pain.

If you are having trouble swallowing or breathing, surgeries to stretch or remove scarred tissue are possible.

Numbness, tingling, dizziness, paralysis, deafness

Numbness, tingling, or pain in the hands or feet--peripheral neuropathy--may persist for months or years following treatment with vincristine or cisplatin. There is no treatment yet for this disorder, although pain management techniques may help.

Treatment with the aminoglycoside antibiotics gentamycin, tobramycin, amikacin, or with vancomycin for infections that arise during cancer treatment can result in temporary or permanent hearing loss, vertigo, dizziness, or ringing in the ears. These disorders can be treated with surgery, drugs, rehabilitation exercises, or noise-blocking devices.

Temporary or permanent paralysis called ascending myelopathy has been linked to the use of methotrexate in the spine, especially in children. If treated promptly with steroids, the condition may improve, but the paralysis also can become permanent.

An NHL survivor who was treated for hybrid NHL/ALL for more than two years describes the effect of treatment on his hands:

I have been on vincristine for almost two years now, and although I have felt that at times I have slight problems in flipping through pages or typing due to numbness and other effects in the fingers, the effects were not significant. But today was a rude awakening. I am taking my Ph.D. qualifying exams this weekend, and one of the exams is pretty stressful in terms of the number of questions to be answered in the allotted four hours. So, today I tried to simulate the exam situation and write one answer in the given time and guess what? First, I couldn't write as fast as I used to in my precancer life, and second, since I have not written at the speed required in exams for a long, long time, my wrist and shoulder started hurting within thirty minutes. Finally, I just couldn't grip the pen well enough to write neat and fast and have been feeling dullness in my fingertips since. This is the first time I can feel the effects in this magnitude and the timing is ridiculously bad.

Pain

Pain in various parts of the body, such as the back and legs, can result from bone and nerve damage owing to radiotherapy or from long pressure of tumors on nerve pathways.

Peripheral neuropathy, causing pain in the hands and feet, can result from treatment with vincristine or cisplatin.

If you have chronic, low-grade pain, don't try to ignore it. There are ways to address pain so that it does not become worse or cause permanent damage. Moreover, chronic pain, even low-level pain, has an affect on mood and performance that you might not notice if pain gets gradually worse or if you've been dealing with it for a long time.

If you have persistent pain of any magnitude, you might consider consulting a pain specialist or pain clinic for a multi-modal approach to pain control that may include pain medication, surgery, behavior modification, pain control devices such as implantable nonaddictive morphine pumps or electrical stimulators, ultrasound treatments, or relaxation training.

All of the following groups offer support or referrals for pain management:

• American Academy of Pain Medicine: (708) 966-9510
• American Society of Clinical Hypnosis: (847) 297-3317
• American Pain Society: (847) 966-5595
• American Society of Anesthesiologists: (847) 825-5586
• National Chronic Pain Outreach Association: (301) 652-4948
• Agency for Health Care Policy and Research: (800) 358-9295

Radiation fibrosis

Radiation fibrosis is the formation of fibrous scar tissue within the body, caused by the immune system reacting to radiation. It unfolds over months or years. This fibrous tissue is knotty and stiff, and interferes with an organ's ability to do its job. For example, fibrosis in the esophagus can cause it to narrow and can cause the muscles for swallowing to be less functional. Fibrosis of tissue in the chest can cause the heart to pump less efficiently and can cause pain upon arm movement. Fibrosis in the sexual organs can interfere with fertility or sexual pleasure. Certain drugs, such as Taxol, when administered along with radiotherapy, can worsen fibrosis.

There is some recent evidence that administering steroid drugs simultaneously with radiotherapy can reduce the body reaction that causes fibrosis, but it appears that not many doctors know of, or believe in, this circumvention yet. Administering steroids after radiation therapy must be done promptly upon noticing the onset of fibrosis, as delay causes steroid therapy to be ineffective.

Recent research with hyperbaric oxygen has shown some promise in reducing the negative effect of radiotherapy on certain tissues such as blood vessels in the brain.

Recall sensitivity

Certain body tissues are permanently affected by chemotherapy or radiation therapy, becoming permanently sensitized, and may react with swelling and soreness if chemotherapy is re-administered months or years later. This is called recall sensitivity. It's a physical, not a psychological, phenomenon.

For instance, if chemotherapy happens to leak accidentally from an arm vein (extravasation) during infusion, the skin into which it leaks may swell and hurt if chemotherapy is administered again--even if it's years later, and even if the other arm is used.

When chemotherapy is administered following radiotherapy, previously irradiated tissue may become sore, even if it's nowhere near the injection site.

Ask your oncologist about precautions that you and she can use to avoid this problem.

Second cancers

One of the most serious risks associated with cancer treatment is the risk of developing a second cancer. These fall broadly into two categories: leukemias and second solid tumors.

Treatment-related leukemias (t-MDS, t-AML)

Certain chemotherapeutic agents, specifically the alkylating drugs such as cyclophosphamide and epipodophyllotoxins such as etoposide are known to increase the risk of subsequent leukemia, with higher doses and longer use of these drugs incurring higher risk. For NHL survivors, these higher chemotherapy doses usually are encountered only in the conditioning regimens for bone marrow or stem cell transplantation, not in the dosage normally found in CHOP, for example.

Some leukemias that follow treatment emerge abruptly and progress rapidly within three years of treatment as an obvious leukemia (t-AML). Some emerge slowly five to twelve years later, perhaps beginning as myelodysplasia (MDS), an imbalance of blood components that often becomes a leukemia.

Radiation therapy does not appear to increase the risk of leukemia unless the spleen is irradiated, or unless all bone marrow is irradiated as preparation for a bone marrow or stem cell transplant.

At this time, the only known cure for treatment-related leukemia or myelodysplasia is bone marrow or stem cell transplantation using donor marrow. Myelodysplasia that is treated as soon as possible with transplantation is more successfully eradicated than the treatment of a frank, rapid leukemia or of myelodysplasia that has advanced to leukemia.

Treatment-related solid tumors (second solid tumors)

Radiation therapy is linked to the development of second solid tumors such as Hodgkin's lymphoma, testicular, breast, kidney, and lung cancers, and certain tumors within the spleen or marrow. Second tumors that arise following radiotherapy almost always arise in or near sites of previous irradiation, called radiation ports. Rates of radiation-induced tumors begin to rise about fifteen years after treatment. Radiation-induced tumors are more likely among childhood cancer survivors than among those treated as adults.

The chemotherapeutic agent cyclophosphamide has been linked to the subsequent development of bladder cancer. Co-administration of the drug Mesna may protect the bladder from this risk.

One study of Japanese patients noted a link between cirrhosis that develops following radiation therapy or chemotherapy and subsequent primary liver cancer. This kind of tumor may be more likely to occur among Asians harboring the hepatitis C virus.

Sexuality and fertility

Long-term damage to sexuality and fertility is possible when NHL is treated with certain chemotherapies or with radiotherapy to the pelvic organs. Difficulties such as failed ovulation, failed conception, irregular menses, inability to achieve or maintain an erection, and pain during intercourse are possible.

Shingles

All who had chicken pox as a child, and cancer survivors who receive marrow from a donor who had chicken pox, harbor within their nerve cells a herpesvirus called varicella Zoster, the virus that causes chicken pox and shingles, two manifestations of the same illness.

There are many human herpesviruses; varicella Zoster is just one. It should not be confused with the genital herpesvirus that is transmitted sexually.

When the immune system becomes suppressed or dysfunctional, varicella Zoster may re-emerge from nerve endings, causing quite terrible pain and blisters called herpes Zoster or shingles. Immune dysfunction is common among those who have lymphoma, leukemia, myeloma, AIDS, or those on immunosuppressive drugs following a transplant. The virus can affect any or all nerve endings within the entire body, but it is most likely to appear along the side of the face, neck, arm, or side of the body. Although 10 to 20 percent of those with shingles may never produce blisters, they will still experience itching or pain, or both. The blisters tend to appear in a line, following the path of nerves.

Shingles that affect the eye can cause temporary or permanent blindness.

As soon as symptoms appear, call your doctor. An antiviral medication such as acyclovir, and perhaps pain medication as well, should be started promptly. It is not unusual to require codeine or even morphine briefly for severe shingles episodes.

Shingles normally heal within four to six weeks, but some patients experience lingering pain for years afterward. If this happens, a procedure called a nerve block or glycerine block can be performed by a neurosurgeon. It should alleviate pain for several months and can be repeated if needed.

Shortness of breath

Shortness of breath can be caused by a number of treatments used for some NHL patients. See the sections regarding heart damage, lung damage, low blood counts, or radiation fibrosis.

Skeletal damage

Radiation therapy can damage bone, causing pain, fracture, and asymmetric growth, such as curvature of the spine.

Long-term high-dose steroid therapy with drugs like prednisone can damage bone, causing avascular necrosis of bone, a painful condition that can be treated with joint replacement.

I have extensive bone damage from prednisone which I took during first-line treatment and then again after my bone marrow transplant for a lung condition. I have bone infarcts on my sacrum, femurs, and tibias, as well as osteonecrosis in my hips, sacrum, and knees. I have considerable pain and take narcotics daily to function.

Recently developed drug treatments for myeloma such as Pamidronate (Aredia) eventually may be used to rebuild bone among those suffering from other illnesses, but in some cases, joint replacement or prosthetic implants to provide skeletal support may be necessary.

Skin

Many causes are found for skin problems that follow NHL treatment, from garden-variety dry skin, perhaps owing to altered absorption of nutrients, to radiation- or chemotherapy-induced thinning and scarring. Other problems include re-emergence of autoimmune disorders such as psoriasis, and graft-versus-host disease following a transplant. Rarely, immune-suppressed survivors of NHL may contract mycobacterial or fungal infections that resist treatment.

If you can't find relief easily, ask your oncologist to refer you to a dermatologist who has experience in treating cancer survivors.

Stomach or intestinal distress

Long-term damage from irradiation of the abdomen may appear as diarrhea, or as constipation from narrowed, tightened intestines or damaged nerves. Medication for diarrhea may help the former, and surgery may correct the latter.

Constipation from immobility or from use of pain medications may also be a lingering effect. Exercise, stool softeners, or a switch in pain medication may ease these effects.

Nausea related to liver damage from chemotherapy may occur. Changes in medication or diet to improve liver function may reduce nausea. In extreme cases, liver transplantation may be recommended.

Pain and constipation may result from the use of chemotherapy drugs that damage nerve cells, such as vincristine.

Surgical complications

A number of late effects linked to prior surgeries are possible owing to the development of scar tissue called adhesions, unavoidable damage to nerves, or use of improper surgical technique. Ask your doctor about any symptoms you're having that you suspect may be related to a prior surgery. Adhesions, for example, can be corrected with follow-up surgery.

Swollen arms, legs, hands, feet

Swollen extremities can result from several of the treatments used for NHL or can be caused by lymph node removal during diagnostic surgery. See the sections above on heart, liver, or kidney damage, or lymphedema.

Thyroid dysfunction

The thyroid gland is a butterfly-shaped organ that wraps around the trachea. When it has been damaged by cancer treatment, it may become underactive, overactive, or cancerous.

Irradiation of the head, neck, or chest can cause the thyroid gland to fail during or after therapy. Irradiation of structures near the thyroid can affect the thyroid because radiation scatter, a ricochet effect among body organs, is difficult to control.

Certain chemotherapies, including some of the interferons or interleukin-2, can cause the thyroid gland to fail during or after therapy

Symptoms of an underactive thyroid (hypothyroidism) may include lethargy, dry skin, numbness in hands or feet, weight gain, mental slowness, sleepiness, depression, immune suppression, intolerance of cold, and loss of hair or altered hair quality. These symptoms also resemble the side effects of many cancer treatments, but thyroid blood levels can be tested to distinguish low thyroid function from transient side effects. Hypothyroidism that is not caused by a tumor is safely and quickly remedied by replacing the missing thyroid hormones using thyroxine, an oral medication.

Symptoms of an overactive thyroid (hyperthyroidism) may include weight loss (or, rarely, gain), excessive appetite, irritability, intolerance of heat, insomnia, rapid heartbeat, high blood pressure, protruding eyes, stroke, and loss of hair or altered hair quality. These symptoms resemble the side effects of prednisone use, but thyroid blood levels can be tested to distinguish overactive thyroid function from the transient side effects of steroid use. Hyperthyroidism that is not caused by a tumor can be treated with drugs that block thyroid hormone activity, such as Tapazole; with high blood pressure medicine to control symptoms temporarily; via surgery to remove the thyroid; or by injections of radioactive iodine-131 to destroy overactive thyroid tissue.

A malignant tumor of the thyroid gland may produce a mixture of the above symptoms. Surgical removal of half or all of the thyroid gland is used to cure thyroid malignancy. This surgery is very safe, and is curative in over 95 percent of cases, depending on tumor stage and histologic subtype.

Thyroid disease also can be linked to dysfunctions of the adrenal gland that resemble Addison's and Cushing's diseases, or to damage of brain organs such as the pituitary.

If you suspect thyroid disease, your doctor will order imaging studies. Tell all medical personnel involved, especially the radiologist who will read your scans, that you are an NHL survivor, because relapses of certain NHLs such as the MALT NHLs can occur within the thyroid gland.