The Otherside of Transplant

                                             The Other Side of Transplant

                                                     PKGhatak,MD

                                           

                                       
Many diseases fail to respond to the best possible treatment and usually end in organ failure. Research and advances in medicine have made it possible to extend life by the use of Mechanical Ventilators, Renal Dialysis Machines, Artificial Heart Pacemakers, and Mechanical Heart Pumps. These devices are life-extenders but far from a cure. Implanting a functioning organ from a recently deceased person came next, and kidneys from living donors and a portion of the liver are also accepted. Transplants are now standard practice for end-stage organ failure. But a shortage of available organs and rejection of the transplanted organs by the recipient's body, lead to further refinements of patient selection, organ harvest, post-transplant immunosuppression medications, and prevention of infections.

After the patient's specialist recommends transplantation, the patient is interviewed and thoroughly examined by a transplant team. The team is made up of surgeons, physicians, immunologists, nurses, pharmacists, psychologists, social workers and others. The patient is well advised about risks, future complications, and the requirement of strict compliance with the treatment regimen. Once selected for transplant, then the patient waits and waits - till the day an organ is available. For most patients, this period is long but is full of hope and sweet dreams - a promise to return to a normal life.

Shortly after successful transplantation, the initial elation is replaced by anxiety. Fear of catching an infection, and concerns about rejection become unconscious preoccupations. Some of those are discussed here:

Rejection:
Lung transplant patients have the most frequent rejection incidents, and the kidney the least, liver, pancreas, and heart are in between. The rejections are of two types- Acute and Chronic. About 50 to 80 % of transplant patients will have at least one episode of rejection in the post-transplant period.

Acute Rejection: This usually happens within a year of transplantation. In a kidney transplant, the incidence is 10 % in patients who have undergone the pre- transplant immunosuppressant therapy, in non- treatment group the incidence is 20 -30 %. In Lung transplants the rejection incidence is over 50% for one episode, often multiple incidences occur and lead to bronchiolitis obliterate – a fatal disease. In cases of heart, the incidence is over 50% and 2 to 3 incidences occur in the same patient. In liver transplant cases, the first incidence of rejection often occurs within 2 weeks.
To reverse the acute rejection the patient needs to be hospitalized. Laboratory blood, urine tests, X-rays, scans, ultrasound tests, etc. may not be enough to make a diagnosis. A biopsy of the transplant organ is usually required for each episode of rejection. The procedure is painful and has associated risks.
The treatment of acute rejection includes biological agents. These are:
  
Polyclonal Antibodies:    Administered via a central vein. Chills, high fever, joint pain are common and symptoms of acute serum sickness may develop, occasionally anaphylaxis is seen.
Monoclonal Antibodies: Can be given via a peripheral vein. The side effects are milder than polyclonal antibodies.
Alemtuzumab, Belatacept, Rituximab and other agents are in the process of development.

Chronic Rejection: This may occur at any time for the life of the transplant organ. The incidents vary according to the organ transplanted. The symptoms of chronic rejection are mild and deterioration of the function of the transplant organ is the usual sign. A biopsy of the organ may be required. Chronic rejection is a progressive insidious process and is due to atrophy of the transplant organ and fibrosis.
To prevent chronic rejection patients are placed on immunosuppressant therapy which consists of several drugs -

Drugs used:
Usually, more than one drug is used, often requiring a change of medications and a close follow up for the rest of patients' lives. The following drugs are commonly used. -
Glucocorticoids: Initially given in large dosages by intravenously then switched orally. The dosage is tapered slowly over time and the maintenance dose is around 10 mg a day. This drug has significant side effects – Osteoporosis, compression fractures of the spine and hip fractures, cataracts, and fungal infections.
Cyclosporine: administered orally. It is toxic to kidneys, decreases renal function over time, gum hyperplasia, increases blood potassium and elevates blood sugar are commonly seen. Increase hair growth often occurs. Dose adjustments are made based on the blood levels of the drug.
Tacrolimus: It is also toxic to kidneys. It increases blood sugar. It is given orally. Dosage adjustments are made on blood levels.
Sirolimus: It is given orally and has no renal toxicity. It increases blood lipids, causes oral ulcers and anemia. Blood levels are obtained for dosage adjustment.
Azathioprine (Imuran): It may produce bone marrow suppression. It is administered orally.
Mycophenolic Acid: It causes GI disturbances, nausea, abdominal pain and low white cell and platelet counts. It is available as pills.
Drug Interactions:
Cyclosporin and Tacrolimus are metabolized faster by Anti TB drugs and blood levels fall below the therapeutic range, whereas, blood levels reach toxic levels when used with calcium channel blockers, antifungal drugs, erythromycin and clarithromycin. Cyclosporin and Tacrolimus are nephrotoxic and should not be combined. Cyclosporin and sirolimus should be given at least 6 hrs. apart to prevent excessive blood levels of sirolimus. Mycophenolic acid blood levels are higher when used with tacrolimus or sirolimus concurrently.


Infection:
Cytomegalovirus (CMV): The infection is often due to the reactivation of an old infection. If the transplant organ is seropositive for CMV, implanted in a seronegative recipient then it becomes a serious problem and multi system failure may occur.
Hepatitis B virus (HBV): Patients receiving a liver transplant as a consequence of previous HBV infection are properly monitored and treated to prevent reactivation of infection, otherwise, fulminate hepatitis and liver failure would follow. If a patient is seropositive for HBV, then he becomes ineligible for transplant of organ other than liver.
Hepatitis C Virus (MCV): Risks are similar to HBV infection but the symptoms are milder and the disease progresses slowly.
Ebstein-Barr Virus (EBV): Infections may lead to the development of Lymphoma.
Human Herpes Viruses: (HHV): Infections may lead to renal graft loss and kidney failure.
Fungal Infections: Mucormycosis, Aspergella, Candida infections are common due to immunosuppression.
Cryptococcus: Infection to the brain and meninges lead to a serious situation.

Infection Prophylaxis:
Appropriate medications are given, short or long term, to prevent infections against CMV, HHV, Pneumocystis, Nocardia, and in endemic countries against Tuberculosis.

Malignancy:
The incidence of carcinoma of the skin and lips is high and accounts for 50% of all malignancies in transplant recipients. The incidence of lung cancer, Kaposi sarcoma, renal cell carcinoma, urogenital carcinoma is higher than the general population.
Non-Hodgkin lymphoma accounts for about 25% of all malignancies and is about 40-fold higher than the general population.

Immunization:
Pneumococcal vaccines, Hepatitis B vaccines, yearly Influenza vaccine and Varicella-Zoster vaccine are recommended. Recipients of transplants should never receive any live vaccine.

Organ transplantation should be done only in transplant centers. A transplant team is essential and only dedicated centers can attract and retain the highly qualified and technically super-gifted people. All tests must be done in house and results must be available instantly. A good outcome of implantation depends on patients' full compliance with the medical advice, and such centers have people and follow up protocols for tracking each patient for a very long time.

Transplant of bone marrow, stem cells, cord blood cells, skin, face, fecal, beta cells of the pancreas, and small intestine, etc. are also done but these are not discussed here.

 

 

 

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