curs 3,4, 5 imunologia transplantului

Liver Liver transplantation andtransplantation and

heart heart transplantationtransplantation

Prof. Ileana Prof. Ileana ConstantinescuConstantinescu

The single most effective therapy The single most effective therapy for end –stage liver failure (ESLF) is for end –stage liver failure (ESLF) is liver transplantation (LT).liver transplantation (LT).• European Liver Transplant Registry:European Liver Transplant Registry:

70.000 LT have been performed in 137 centres 70.000 LT have been performed in 137 centres around Europe.around Europe.

UK: UK: currently 680 liver transplants are currently 680 liver transplants are performed yearly.performed yearly. More than 6000 patients have been More than 6000 patients have been transplantedtransplanted

RO: RO: about 30-50-60 LT/year about 30-50-60 LT/year

Unfortunately the supply cannot meet demandUnfortunately the supply cannot meet demand

Indications for LT - adultsIndications for LT - adultsCommon:Common:1.1. Alcoholic liver disease (ALD)Alcoholic liver disease (ALD)2.2. Cryptogenic cirrhosisCryptogenic cirrhosis3.3. Primary biliary cirrhosisPrimary biliary cirrhosis4.4. Primary sclerosing cholangitis (PSC)Primary sclerosing cholangitis (PSC)5.5. Hepatitis (B, C, non-A, non-B)Hepatitis (B, C, non-A, non-B)6.6. Hepatocellular carcinomaHepatocellular carcinoma7.7. Autoimmune hepatitisAutoimmune hepatitis

Indications for LT - adultsIndications for LT - adultsRare:Rare:1.1. HaemochromathosisHaemochromathosis2.2. Wilson’s diseaseWilson’s disease3.3. ΑΑ1-antitrypsin deficiency1-antitrypsin deficiency4.4. Budd-Chiari syndromeBudd-Chiari syndrome5.5. Polycystic diseasePolycystic disease6.6. Hyperoxaluria, familial Hyperoxaluria, familial

hypercholesterolaemiahypercholesterolaemia7.7. Porphyrias, amyloidosis, Porphyrias, amyloidosis,

neuroendocrine tumours (e.g. neuroendocrine tumours (e.g. carcinoid)carcinoid)

Indications for LT in Indications for LT in childrenchildren

• Biliary atresiaBiliary atresia• Familial cholestasis syndromesFamilial cholestasis syndromes• Metabolic disorders:Metabolic disorders:

Cystic fibrosisCystic fibrosis ΑΑ1-antitrypsin deficiency1-antitrypsin deficiency Crigler-Najjar type 1Crigler-Najjar type 1 Wilson’s diseaseWilson’s disease

• Unresectable tumours (e.g. Unresectable tumours (e.g. hepatoblastomas)hepatoblastomas)

• Acute liver failure – viral, drugs (e.g. Acute liver failure – viral, drugs (e.g. paracetamol toxicity), autoimmuneparacetamol toxicity), autoimmune

Contraindications to Contraindications to liver transplantationliver transplantation

Absolute:Absolute:1.1. InfectionInfection2.2. Malignancy outside the hepatobiliary Malignancy outside the hepatobiliary

systemsystem3.3. Secondary hepatic malignancySecondary hepatic malignancy4.4. Active drug or alcohol abuseActive drug or alcohol abuse5.5. Advanced cardiopulmonary diseaseAdvanced cardiopulmonary disease

Contraindications to liver Contraindications to liver transplantationtransplantation

Relative:Relative:1.1. Age over 65 yearsAge over 65 years2.2. Portal vein thrombosisPortal vein thrombosis3.3. Renal failure not associated with liver Renal failure not associated with liver

diseasedisease4.4. Intrahepatic sepsisIntrahepatic sepsis5.5. HIVHIV

Emmergencies for LTEmmergencies for LT Paracetamol poisoningParacetamol poisoning Diuretic-resistant ascitesDiuretic-resistant ascites Hepatopulmonary syndromesHepatopulmonary syndromes Chronic hepatic encephalopathyChronic hepatic encephalopathy Persistent and intractable pruritusPersistent and intractable pruritus Familial amyloidosisFamilial amyloidosis Primary hyperlipidaemiasPrimary hyperlipidaemias Polycystic liver diseasePolycystic liver disease

Work-up for liver transplantationWork-up for liver transplantation

• Assessment for conventional deceased Assessment for conventional deceased donordonor

1.1. Blood groupBlood group2.2. Conventional liver screen/liver biopsy for Conventional liver screen/liver biopsy for

steatosissteatosis3.3. Viral screeningViral screening4.4. HLA typing: HLA-A, B, DRB1HLA typing: HLA-A, B, DRB15.5. Tumor markers: AFP, CA 19-9, CEA, CA 125, Tumor markers: AFP, CA 19-9, CEA, CA 125, CA 15-3, CA 15-3, ββ2-microglobulin, total and free 2-microglobulin, total and free

PSAPSA

Work-up for liver transplantationWork-up for liver transplantation• Assessment for liver donationAssessment for liver donation

1.1. Blood groupBlood group2.2. Conventional liver screen/liver biopsy for Conventional liver screen/liver biopsy for

steatosissteatosis3.3. Viral screeningViral screening4.4. HLA typing: HLA-A, B, DRB1HLA typing: HLA-A, B, DRB15.5. Tumor markers: AFP, CA 19-9, CEA, CA 125, Tumor markers: AFP, CA 19-9, CEA, CA 125,

CA 15-3, CA 15-3, ββ2-microglobulin, total and free PSA2-microglobulin, total and free PSA6.6. To exclude occult thromboembolic disorders: To exclude occult thromboembolic disorders:

abnormalities for PT, protein C, protein S, abnormalities for PT, protein C, protein S, antithrombine III, factor V Leiden, factor VIII, antithrombine III, factor V Leiden, factor VIII, cardiolipin , antiphospholipincardiolipin , antiphospholipin

Immunology of liver Immunology of liver transplantation in the recipienttransplantation in the recipient

AB0 compatibilityAB0 compatibility Viral screeningViral screening Child Pugh score: A, B, CChild Pugh score: A, B, C MELD score (Model for End-stage Liver MELD score (Model for End-stage Liver

Disease)Disease)3.8 x log3.8 x logee (bilirubin mg/dL) + 11.2 x (bilirubin mg/dL) + 11.2 x

logloge e (INR) + 9.6 log(INR) + 9.6 loge e (creatinine (creatinine mg/dL) + 6,4 (aetiology: 0 if mg/dL) + 6,4 (aetiology: 0 if cholestatic or alcoholic, 1 otherwise)cholestatic or alcoholic, 1 otherwise)

Immunology of liver Immunology of liver transplantation in the recipienttransplantation in the recipient

Histocompatibility testing plays little role in selecting an individual Histocompatibility testing plays little role in selecting an individual recipient for LT for a particular donorrecipient for LT for a particular donor

Class I HLA matching may significantly improve Class I HLA matching may significantly improve patient graft survival.patient graft survival.

In the liver tissue In the liver tissue HLA class I antigens HLA class I antigens are to are to be found only on the biliar epithelium, but not be found only on the biliar epithelium, but not on the hepatocyteson the hepatocytes

HLA class II antigens HLA class II antigens are present in Kupffer are present in Kupffer cells and endotelial cells.cells and endotelial cells.

Cytotoxic antibodiesCytotoxic antibodies Crossmatch – a positive crossmatch is Crossmatch – a positive crossmatch is

associated with a higher likelihood of early associated with a higher likelihood of early rejection episodes.rejection episodes.

Liver transplantation for hepatitis C virus Liver transplantation for hepatitis C virus infectioninfection Hepatitis C virus (HCV) infection causes approximately 40 percent of all chronic liver Hepatitis C virus (HCV) infection causes approximately 40 percent of all chronic liver

disease in the United States, and HCV-associated cirrhosis is the most common indication disease in the United States, and HCV-associated cirrhosis is the most common indication for orthotopic liver transplantation (OLT) among adults . HCV infection remains a problem for orthotopic liver transplantation (OLT) among adults . HCV infection remains a problem after transplantation, and recurrent hepatic infection is the leading cause of graft failure.after transplantation, and recurrent hepatic infection is the leading cause of graft failure.

The major issues related to HCV following liver transplantation will be reviewed here. The major issues related to HCV following liver transplantation will be reviewed here. Similar problems arise in patients with HCV who undergo other forms of organ Similar problems arise in patients with HCV who undergo other forms of organ transplantation. transplantation.

The natural history and treatment of HCV, as well as the selection of patients for liver The natural history and treatment of HCV, as well as the selection of patients for liver transplantation, is discussed elsewhere. transplantation, is discussed elsewhere.

EPIDEMIOLOGYEPIDEMIOLOGY Recurrence of hepatitis C virus (HCV) following orthotopic liver transplantation (OLT) occurs Recurrence of hepatitis C virus (HCV) following orthotopic liver transplantation (OLT) occurs

in more than 95 percent of patients. Nucleotide sequence studies of HCV demonstrate that in more than 95 percent of patients. Nucleotide sequence studies of HCV demonstrate that the disease following OLT results from the same viral strain present before OLT. Virologic the disease following OLT results from the same viral strain present before OLT. Virologic reinfection at the time of transplantation is not surprising since almost all patients are reinfection at the time of transplantation is not surprising since almost all patients are viremic at this time . Reinfection occurs during reperfusion of the allograft in the operating viremic at this time . Reinfection occurs during reperfusion of the allograft in the operating room, and viral titers reach pretransplant levels within 72 hours. Furthermore, peripheral room, and viral titers reach pretransplant levels within 72 hours. Furthermore, peripheral monocytes may also harbor virus and act as a source for reinfection of the donor liver. De monocytes may also harbor virus and act as a source for reinfection of the donor liver. De novo infection in previously HCV-negative patients can result from transfusion of blood novo infection in previously HCV-negative patients can result from transfusion of blood products during OLT, but has become rare since 1992 due to blood product screening.products during OLT, but has become rare since 1992 due to blood product screening.

PATHOGENESISPATHOGENESIS Variables that influence the progression of recurrent hepatitis C virus (HCV) following Variables that influence the progression of recurrent hepatitis C virus (HCV) following

orthotopic liver transplantation (OLT) are incompletely understood, but donor orthotopic liver transplantation (OLT) are incompletely understood, but donor characteristics (donor type, age), viral characteristics (genotype, viral load), the characteristics (donor type, age), viral characteristics (genotype, viral load), the inflammatory grade of the explanted liver, and the patient's immune status and inflammatory grade of the explanted liver, and the patient's immune status and immunosuppressive regimen may be important.immunosuppressive regimen may be important.

Overview of dermatologic problems Overview of dermatologic problems following liver transplantationfollowing liver transplantation Liver transplantation recipients, like other solid organ transplantation recipients, have an increased risk of Liver transplantation recipients, like other solid organ transplantation recipients, have an increased risk of

dermatologic problems due to their long-term immunosuppression and benefit from pre-and post-dermatologic problems due to their long-term immunosuppression and benefit from pre-and post-transplantation screenings, and management by a dermatologist and dermatologic care should be integrated transplantation screenings, and management by a dermatologist and dermatologic care should be integrated into the comprehensive, multidisciplinary care of liver transplantation recipient. Cutaneous findings include into the comprehensive, multidisciplinary care of liver transplantation recipient. Cutaneous findings include aesthetic alterations, infections, precancerous lesions, and malignancies. The severity of skin alterations ranges aesthetic alterations, infections, precancerous lesions, and malignancies. The severity of skin alterations ranges from benign, unpleasant changes to life-threatening conditions . In addition to skin cancer diagnosis and from benign, unpleasant changes to life-threatening conditions . In addition to skin cancer diagnosis and management, visits with a dermatologist serve to educate and improve the patient's sun-protection behavior.management, visits with a dermatologist serve to educate and improve the patient's sun-protection behavior.

Among all solid organ transplantations, liver transplantation requires the least amount of immunosuppression, Among all solid organ transplantations, liver transplantation requires the least amount of immunosuppression, sometimes even permitting its complete cessation. As a result, patients who have undergone liver sometimes even permitting its complete cessation. As a result, patients who have undergone liver transplantation tend to have fewer dermatologic complications compared with other solid organ transplantation transplantation tend to have fewer dermatologic complications compared with other solid organ transplantation recipients. However, due to the large volume of the liver, patients undergoing liver transplantation receive more recipients. However, due to the large volume of the liver, patients undergoing liver transplantation receive more donor lymphocytes than kidney, heart, or lung transplantation recipients. Because of the immunosuppression, donor lymphocytes than kidney, heart, or lung transplantation recipients. Because of the immunosuppression, the transplanted lymphocytes proliferate and rarely trigger graft-versus-host-disease .the transplanted lymphocytes proliferate and rarely trigger graft-versus-host-disease .

This topic will provide an overview of dermatologic disorders that may be seen following liver transplantation. A This topic will provide an overview of dermatologic disorders that may be seen following liver transplantation. A detailed discussion of skin cancer following solid organ transplantation and the general management of patients detailed discussion of skin cancer following solid organ transplantation and the general management of patients following liver transplantation are discussed separately. following liver transplantation are discussed separately.

EFFECT OF TRANSPLANTATION ON PREEXISTING DERMATOLOGIC DISORDERSEFFECT OF TRANSPLANTATION ON PREEXISTING DERMATOLOGIC DISORDERS Patients undergoing liver transplantation may have preexisting dermatologic disorders that are subsequently Patients undergoing liver transplantation may have preexisting dermatologic disorders that are subsequently

affected by transplantation. In many cases, the disorders improve either as a result of removal of the diseased affected by transplantation. In many cases, the disorders improve either as a result of removal of the diseased liver or because of the immunosuppression patients receive.liver or because of the immunosuppression patients receive.

Dermatologic manifestations of liver diseaseDermatologic manifestations of liver disease — In patients with dermatologic lesions related to cirrhosis or — In patients with dermatologic lesions related to cirrhosis or associated with specific forms of liver disease, transplantation often leads to improvement in the dermatologic associated with specific forms of liver disease, transplantation often leads to improvement in the dermatologic findings .findings .

Heart transplantationHeart transplantation• Indications – adultsIndications – adults1.1. Coronary-related heart failureCoronary-related heart failure2.2. Cardiomyopathies : valvular, mixt Cardiomyopathies : valvular, mixt

diagnoses, adult congenital, diagnoses, adult congenital, retransplantationretransplantation

• Indications – paediatrics (<16 Indications – paediatrics (<16 years)years)

1.1. CardiomyopathyCardiomyopathy2.2. Congenital heart diseaseCongenital heart disease

Recipient assesment Recipient assesment protocol for heart protocol for heart transplantationtransplantation

• Full blood count, plateletes, coagulation Full blood count, plateletes, coagulation screeningscreening

• Blood groupBlood group• Ureea, electrolytes, liver function, thyroid Ureea, electrolytes, liver function, thyroid

functionfunction• MicrobiologyMicrobiology• Viral screeningViral screening• Fasting glucose and lipidsFasting glucose and lipids• ECGECG• Chest X RayChest X Ray• Estimation of peak O2 consumption Estimation of peak O2 consumption

(VO2max)(VO2max)• Carotid/peripheral artery DopplerCarotid/peripheral artery Doppler

Recipient assessment protocol Recipient assessment protocol for heart transplantationfor heart transplantation

AB0 compatibilityAB0 compatibility Immunological matchingImmunological matching

Anti-HLA antibodies ≈ 10%Anti-HLA antibodies ≈ 10% > 25% → rejection> 25% → rejection

HLA typing for A, B, DRB1HLA typing for A, B, DRB1 CrossmatchCrossmatch Chronic transplant dysfunction in transplanted hearts Chronic transplant dysfunction in transplanted hearts

remains the most common cause of graft loss after remains the most common cause of graft loss after the first year postTxthe first year postTx..

Acute cardiac allograft rejectionAcute cardiac allograft rejectionINCIDENCE AND OUTCOMESINCIDENCE AND OUTCOMES Acute rejection is a common problem after heart transplantation, particularly early Acute rejection is a common problem after heart transplantation, particularly early

after transplantation. Most cases are due to cellular rejection. Antibody-mediated after transplantation. Most cases are due to cellular rejection. Antibody-mediated (noncellular, vascular, humoral) rejection is a less well understood and less easily (noncellular, vascular, humoral) rejection is a less well understood and less easily diagnosed process, but potentially produces morbidity .diagnosed process, but potentially produces morbidity .

The 2009 report from the Registry of the International Society for Heart and Lung The 2009 report from the Registry of the International Society for Heart and Lung Transplantation (ISHLT) of patients with one-year follow-up between July 2004 and July Transplantation (ISHLT) of patients with one-year follow-up between July 2004 and July 2008 found that 21 to 30 percent were treated for rejection during the first year after 2008 found that 21 to 30 percent were treated for rejection during the first year after transplantation. This represents an underestimate for overall rejection, since the transplantation. This represents an underestimate for overall rejection, since the Registry does not collect data on mild rejection episodes (grade 1 R) or on antibody-Registry does not collect data on mild rejection episodes (grade 1 R) or on antibody-mediated rejection. mediated rejection.

In the ISHLT report, among deaths occurring between January 1992 and June 2008, In the ISHLT report, among deaths occurring between January 1992 and June 2008, acute rejection accounted for 6 percent of deaths in the first 30 days, 12 percent from acute rejection accounted for 6 percent of deaths in the first 30 days, 12 percent from 31 days to one year, 10 percent from one year to three years, and less than 2 percent 31 days to one year, 10 percent from one year to three years, and less than 2 percent at more than five years. The contribution of rejection to post-transplant mortality has at more than five years. The contribution of rejection to post-transplant mortality has decreased over time. This is primarily due to improvements in maintenance decreased over time. This is primarily due to improvements in maintenance immunosuppression and in the diagnosis and treatment of rejection. Nevertheless, immunosuppression and in the diagnosis and treatment of rejection. Nevertheless, acute heart allograft rejection remains an important clinical problem.acute heart allograft rejection remains an important clinical problem.

This topic will review the risk factors for and the clinical features and diagnostic This topic will review the risk factors for and the clinical features and diagnostic evaluation of acute cellular rejection in the heart transplant recipient. The treatment evaluation of acute cellular rejection in the heart transplant recipient. The treatment of acute rejection is discussed separately. of acute rejection is discussed separately.

RISK FACTORSRISK FACTORS Although acute cellular rejection is always a potential concern in a heart transplant Although acute cellular rejection is always a potential concern in a heart transplant

recipient, the likelihood of a rejection episode is influenced by several factors, recipient, the likelihood of a rejection episode is influenced by several factors, particularly the time after transplantation.particularly the time after transplantation.

TreatmentTreatment Despite the use of potent immunosuppressive agents both immediately after cardiac Despite the use of potent immunosuppressive agents both immediately after cardiac

transplantation and during long-term maintenance, acute rejection remains an transplantation and during long-term maintenance, acute rejection remains an important problem. Cardiac transplant recipients have an average of two to three important problem. Cardiac transplant recipients have an average of two to three episodes in the first year after transplantation, with 50 to 80 percent of patients episodes in the first year after transplantation, with 50 to 80 percent of patients experiencing at least one rejection episode. Acute cellular rejection is most likely to experiencing at least one rejection episode. Acute cellular rejection is most likely to occur in the first three to six months, with the incidence declining significantly after occur in the first three to six months, with the incidence declining significantly after this time.this time.

The diagnosis of acute cellular cardiac allograft rejection is generally made by The diagnosis of acute cellular cardiac allograft rejection is generally made by endomyocardial biopsy performed either routinely or because of suggestive endomyocardial biopsy performed either routinely or because of suggestive symptoms.symptoms.

ISHLT grading systemISHLT grading system — The endomyocardial biopsy is graded using the International — The endomyocardial biopsy is graded using the International Society for Heart and Lung Transplantation (ISHLT) nomenclature adopted in 1990 Society for Heart and Lung Transplantation (ISHLT) nomenclature adopted in 1990 and revised in 2004. and revised in 2004.

For acute cellular rejection:For acute cellular rejection: Grade 0 — no rejectionGrade 0 — no rejection Grade 1 R, mild — Interstitial and/or perivascular infiltrate with up to one focus of Grade 1 R, mild — Interstitial and/or perivascular infiltrate with up to one focus of

myocyte damagemyocyte damage Grade 2 R, moderate — two or more foci of infiltrate with associated myocyte Grade 2 R, moderate — two or more foci of infiltrate with associated myocyte

damagedamage Grade 3 R, severe — diffuse infiltrate with multifocal myocyte damage, with or Grade 3 R, severe — diffuse infiltrate with multifocal myocyte damage, with or

without edema, hemorrhage, or vasculitiswithout edema, hemorrhage, or vasculitis Grade 1 R includes grades 1A, 1B, and 2 in the 1990 system; grade 2 R was grade 3A; Grade 1 R includes grades 1A, 1B, and 2 in the 1990 system; grade 2 R was grade 3A;

and grade 3 R was grades 3B and 4and grade 3 R was grades 3B and 4

Indications and contraindications for Indications and contraindications for cardiac transplantationcardiac transplantation

Cardiac transplantation is the treatment of choice for many patients with end-stage heart Cardiac transplantation is the treatment of choice for many patients with end-stage heart failure (HF) who remain symptomatic despite optimal medical therapy. Risk stratification of failure (HF) who remain symptomatic despite optimal medical therapy. Risk stratification of patients with end stage HF is pivotal for transplant candidate selection. The primary indications patients with end stage HF is pivotal for transplant candidate selection. The primary indications for cardiac transplantation along with the specific inclusion and exclusion criteria are discussed for cardiac transplantation along with the specific inclusion and exclusion criteria are discussed here.here.

Prognosis after cardiac transplantation and treatment of refractory HF are discussed separately. Prognosis after cardiac transplantation and treatment of refractory HF are discussed separately.

WAITING LIST AND ALLOCATIONWAITING LIST AND ALLOCATION The Registry of the International Society for Heart and Lung Transplantation reported 4196 The Registry of the International Society for Heart and Lung Transplantation reported 4196

heart transplants worldwide in 2012.This is probably an underestimate, as reporting to the heart transplants worldwide in 2012.This is probably an underestimate, as reporting to the registry is voluntary outside of the United States. In the United States, where reporting to the registry is voluntary outside of the United States. In the United States, where reporting to the United Network Of Organ Sharing (UNOS) has been mandatory for the past two decades, the United Network Of Organ Sharing (UNOS) has been mandatory for the past two decades, the number of United States heart transplants performed has been stable at approximately 2300 number of United States heart transplants performed has been stable at approximately 2300 cases annually .The majority of centers perform between 10 and 19 heart transplants per year.cases annually .The majority of centers perform between 10 and 19 heart transplants per year.

The number of transplant centers has decreased from 243 in 1996 to 204 in 2007. The ongoing The number of transplant centers has decreased from 243 in 1996 to 204 in 2007. The ongoing organ donor shortage has been the major limitation to the growth of this therapy. Due to this organ donor shortage has been the major limitation to the growth of this therapy. Due to this critical organ shortage, the recipient selection process and donor allocation system have critical organ shortage, the recipient selection process and donor allocation system have involved both clinical and ethical issues.involved both clinical and ethical issues.

Donor allocationDonor allocation — In an effort to ensure equitable distribution of donor hearts, UNOS (a — In an effort to ensure equitable distribution of donor hearts, UNOS (a private organization under contract to the federal government) has created and regularly private organization under contract to the federal government) has created and regularly updates an organ allocation system (Organ Procurement and Transplantation Network). This updates an organ allocation system (Organ Procurement and Transplantation Network). This system delineates prioritization rules that take into account the clinical severity of illness, time system delineates prioritization rules that take into account the clinical severity of illness, time accrued on the wait list, blood type compatibility, and geographic distance. With heart accrued on the wait list, blood type compatibility, and geographic distance. With heart procurement, the duration of ischemic time for the donor heart is a limiting factor in organ procurement, the duration of ischemic time for the donor heart is a limiting factor in organ retrieval, with ischemic times greater than four hours associated with a higher rate of primary retrieval, with ischemic times greater than four hours associated with a higher rate of primary graft failure. Accordingly, geographic distance between the donor hospital and the transplant graft failure. Accordingly, geographic distance between the donor hospital and the transplant center is measured in 500 nautical mile circular concentric zones. center is measured in 500 nautical mile circular concentric zones.

Prospective HLA matching of donor and recipient is not usually performed Prospective HLA matching of donor and recipient is not usually performed for heart and heart-lung transplants. In a multi-centre study statistically for heart and heart-lung transplants. In a multi-centre study statistically significant improved survival with the better-matched heart grafts was significant improved survival with the better-matched heart grafts was found. In a small series of heart grafts it was also found that the found. In a small series of heart grafts it was also found that the improvement with HLA matching was confined to male recipients who were improvement with HLA matching was confined to male recipients who were not blood group O. not blood group O.

Heart graft recipients with wide panel reactive antibody had worse graft Heart graft recipients with wide panel reactive antibody had worse graft survival one year after transplant than the unsensitized. In several studies survival one year after transplant than the unsensitized. In several studies patients with a positive cross-match had a significantly lower survival rate patients with a positive cross-match had a significantly lower survival rate than those with a negative cross-match.than those with a negative cross-match.

It is suggested that, minimally, pre-transplant screening and prospective It is suggested that, minimally, pre-transplant screening and prospective cross-matching of highly sensitised patients is necessary.cross-matching of highly sensitised patients is necessary.

Prevention and treatment of cardiac allograft Prevention and treatment of cardiac allograft vasculopathyvasculopathy Cardiac transplantation is the definitive therapy for eligible patients with end-stage heart Cardiac transplantation is the definitive therapy for eligible patients with end-stage heart

failure. The major limitations to survival in the early post-transplant period (first year) are failure. The major limitations to survival in the early post-transplant period (first year) are nonspecific graft failure, multiorgan failure, acute rejection, and infection . Beyond the nonspecific graft failure, multiorgan failure, acute rejection, and infection . Beyond the first year, cardiac allograft vasculopathy (CAV, also called transplant coronary artery first year, cardiac allograft vasculopathy (CAV, also called transplant coronary artery disease or cardiac transplant vasculopathy) is among the top three causes of death. disease or cardiac transplant vasculopathy) is among the top three causes of death. Approximately 30 percent of patients have angiographic coronary artery disease at five Approximately 30 percent of patients have angiographic coronary artery disease at five years and 50 percent at 10 years, with the incidence increasing progressively with time. years and 50 percent at 10 years, with the incidence increasing progressively with time.

The pathogenesis of CAV will be reviewed here. The diagnosis, prevention, and treatment The pathogenesis of CAV will be reviewed here. The diagnosis, prevention, and treatment of this disease are discussed separately. of this disease are discussed separately.

PATHOLOGYPATHOLOGY Cardiac allograft vasculopathy (CAV) is a panarterial disease confined to the allograft and Cardiac allograft vasculopathy (CAV) is a panarterial disease confined to the allograft and

is characterized by diffuse concentric longitudinal intimal hyperplasia in the epicardial is characterized by diffuse concentric longitudinal intimal hyperplasia in the epicardial coronary arteries and concentric medial disease in the microvasculature . In contrast, coronary arteries and concentric medial disease in the microvasculature . In contrast, traditional atherosclerosis is focal, noncircumferential, and most often observed traditional atherosclerosis is focal, noncircumferential, and most often observed proximally in the epicardial vessels.proximally in the epicardial vessels.

Transplant recipients also frequently develop proximal coronary artery disease. However, Transplant recipients also frequently develop proximal coronary artery disease. However, these lesions more closely resemble traditional atherosclerosis pathologically and these lesions more closely resemble traditional atherosclerosis pathologically and probably evolve from pre-existing disease in the donor heart that is accelerated by the probably evolve from pre-existing disease in the donor heart that is accelerated by the plethora of cardiac risk factors after transplantation.plethora of cardiac risk factors after transplantation.

Serial intravascular (intracoronary) ultrasound testing has shown that most of the intimal Serial intravascular (intracoronary) ultrasound testing has shown that most of the intimal thickening occurs during the first year after transplantation. Lumen loss is also due to thickening occurs during the first year after transplantation. Lumen loss is also due to arterial remodeling, with early expansion and late constriction of the external elastic arterial remodeling, with early expansion and late constriction of the external elastic membrane areamembrane area

Basics of Stem Cell Basics of Stem Cell TransplantTransplant

Prof. Ileana ConstantinescuProf. Ileana Constantinescu

BackgroundBackground First successful transplants—late First successful transplants—late

1960s1960s 30,000-40,000 transplants 30,000-40,000 transplants

performed yearly worldwideperformed yearly worldwide >20,000 patients have survived >20,000 patients have survived

>5 years>5 years

Lazarus HM. Autologous and allogeneic transplantation procedures for hematologic malignancies. Manual of Clinical Hematology, 3rd edition 2002:399-409

Graft SourcesGraft Sources Allogeneic: from another personAllogeneic: from another person Syngeneic: from an identical twinSyngeneic: from an identical twin Autologous: from the patientAutologous: from the patient

Choice of graft is based on Choice of graft is based on disease type, patient condition, disease type, patient condition, donor compatibility and healthdonor compatibility and health

Graft SourcesGraft Sources Autologous TransplantAutologous Transplant

– No evidence of disease in the blood or No evidence of disease in the blood or bone marrowbone marrow

– Transplant related mortality (TRM) Transplant related mortality (TRM) lowest with autos (<5%)lowest with autos (<5%)

– Relapse rates are higher depending Relapse rates are higher depending on the diseaseon the disease

– Absence of graft versus tumor effectsAbsence of graft versus tumor effects


Graft SourcesGraft Sources Allogeneic TransplantsAllogeneic Transplants

– High TRM (30-50%)High TRM (30-50%)– Lower relapse rates due to graft versus Lower relapse rates due to graft versus

tumor effectstumor effects– Graft versus host effectsGraft versus host effects

Matched Related Donor (siblings)Matched Related Donor (siblings)– 25% chance a sibling will be a match25% chance a sibling will be a match– The more siblings a patient has the better The more siblings a patient has the better

chance for a matchchance for a match


GRAFT VS. HOST DISEASEGRAFT VS. HOST DISEASE This disease occurs when an immunologically competent foreign This disease occurs when an immunologically competent foreign

graft containing T cells reacts against the MHC antigens of an graft containing T cells reacts against the MHC antigens of an immunologically compromised host.immunologically compromised host.

In general, concerns regarding the outcome of transplantation In general, concerns regarding the outcome of transplantation represent a one-way street, namely the potential of the immune represent a one-way street, namely the potential of the immune system of a transplant recipient or host to reject a transplant. An system of a transplant recipient or host to reject a transplant. An interesting reversal of the direction of the immune response interesting reversal of the direction of the immune response occurs, however, when occurs, however, when immunocompetent cells immunocompetent cells (spleen cells) (spleen cells) are transplanted into a host whose immune system is not are transplanted into a host whose immune system is not functioning properly functioning properly (irradiated) (irradiated) and is, therefore, and is, therefore, immunosuppressed.immunosuppressed.

In this case, a phenomenon known as In this case, a phenomenon known as graft vs. host disease graft vs. host disease ensues, where the immunocompetent graft directs an ensues, where the immunocompetent graft directs an immunological assault against the host, sometimes with fatal immunological assault against the host, sometimes with fatal consequences.consequences.

Graft vs. host disease Graft vs. host disease is, therefore, of particular concern in is, therefore, of particular concern in cases of cases of bone marrow transplantationbone marrow transplantation, where , where immunocompetent T cells in the graft tissue can direct a graft immunocompetent T cells in the graft tissue can direct a graft rejection response against the cell surface MHC antigens of a rejection response against the cell surface MHC antigens of a frequently immunocompromised recipient or host.frequently immunocompromised recipient or host.

2929

HLA TypingHLA Typing HLA typing became feasible in HLA typing became feasible in

1960s1960s Linked on chromosome 6Linked on chromosome 6 Inherited as haplotypesInherited as haplotypes 1 in 4 chance a sibling will be 1 in 4 chance a sibling will be

identicalidentical

Copelan EA. Hematopoietic stem-cell transplantation. NEJM 2006;354:1813-1826.

HLA allelesHLA alleles The considerable polymorphism of HLA is well-The considerable polymorphism of HLA is well-

known.known.

HLA polymorphism is reflected by allelic HLA polymorphism is reflected by allelic substitution of many amino acid residues in substitution of many amino acid residues in the polypeptide chains, especially the external the polypeptide chains, especially the external domains which contain the peptide binding domains which contain the peptide binding site.site.

This affects the spectrum of antigenic This affects the spectrum of antigenic peptides presented by the different allelic peptides presented by the different allelic types of HLA molecules and the repertoire of types of HLA molecules and the repertoire of responding T-cells.responding T-cells.

The HLA genetics is The HLA genetics is complexcomplex

HLA polymorphismHLA polymorphism

Expression of HLA polymorphism –TypingExpression of HLA polymorphism –Typing

The transplanted graft represents a continuous The transplanted graft represents a continuous source of HLA alleles that can induce a rejection source of HLA alleles that can induce a rejection response at any time post-transplant.response at any time post-transplant.

HLA matching can have a dualistic effect on HLA matching can have a dualistic effect on transplant outcome: it reduces rejection but transplant outcome: it reduces rejection but conversely, it may promote other HLA-restricted conversely, it may promote other HLA-restricted mechanisms of allograft injury. mechanisms of allograft injury.

HLA MatchingHLA Matching 6/6, 8/8, or 10/106/6, 8/8, or 10/10

– HLA loci on chromosome 6HLA loci on chromosome 6– HLA-A, HLA-B, HLA-C, HLA-DR, HLA-HLA-A, HLA-B, HLA-C, HLA-DR, HLA-

DQ, HLA-DPDQ, HLA-DP ABO incompatibility is not an ABO incompatibility is not an

exclusionexclusion


Interpretation of resultsInterpretation of resultsRecipient D.F.Recipient D.F. Donor D.C.Donor D.C.

HLAHLA HLAHLAA 02-24A 02-24 A 02-24A 02-24

B 18-18B 18-18 B 18-18B 18-18

C 07-07C 07-07 C 07-07C 07-07

DRB1 11-13DRB1 11-13 DRB1 11-13DRB1 11-13

DQB1 03-05DQB1 03-05 DQB1 03-05DQB1 03-05

KIR – B4 genotypeKIR – B4 genotype KIR – B4 genotypeKIR – B4 genotype

KIR –2DL1, 2DL2, 2DL4, 2DL5B, 2DS2, KIR –2DL1, 2DL2, 2DL4, 2DL5B, 2DS2, 2DS3, 2DS42DS3, 2DS4004004, 3DL2, 3DL3, 3DS1, , 3DL2, 3DL3, 3DS1, 2DP1, 3DP12DP1, 3DP1

KIR –2DL1, 2DL2, 2DL4, 2DL5B, 2DS2, KIR –2DL1, 2DL2, 2DL4, 2DL5B, 2DS2, 2DS3, 2DS42DS3, 2DS4004004, 3DL2, 3DL3, 3DS1, , 3DL2, 3DL3, 3DS1, 2DP1, 3DP12DP1, 3DP1

Recipient A.C.Recipient A.C. Donor C.R.Donor C.R.

HLAHLA HLAHLA

A 03-24A 03-24 A 03-24A 03-24B 18-44B 18-44 B 18-44B 18-44C 05-12C 05-12 C 05-12C 05-12DRB1 16-16DRB1 16-16 DRB1 16-16DRB1 16-16DQB1 05-05DQB1 05-05 DQB1 05-05DQB1 05-05DPB1 02-05DPB1 02-05 DPB1 02-05DPB1 02-05KIR – B4 genotypeKIR – B4 genotype KIR – B4 genotypeKIR – B4 genotype

KIR –2DL1, 2DL2, 2DL4, 2DL5BKIR –2DL1, 2DL2, 2DL4, 2DL5B003-006003-006, , 2DS3, 2DS4, 2DL1, 3DL2, 3DL3, 2DP1, 2DS3, 2DS4, 2DL1, 3DL2, 3DL3, 2DP1, 3DP13DP1003003

KIR –2DL1, 2DL2, 2DL4, 2DL5BKIR –2DL1, 2DL2, 2DL4, 2DL5B003-006003-006, , 2DS3, 2DS4, 2DL1, 3DL2, 3DL3, 2DP1, 2DS3, 2DS4, 2DL1, 3DL2, 3DL3, 2DP1, 3DP13DP1003003

Interpretation of resultsInterpretation of results

Interpretation of resultsInterpretation of resultsRecipient F.C. Donor F.E.

HLA HLA

A 02-03 A 02-03

B 07-40 B 07-40

C 01-03 C 01-03

DRB1 04-10 DRB1 04-10

DQB1 03-07 DQB1 03-07

KIR – A genotype KIR – A genotype

KIR – 2DL1, 2DL3, 2DL4, 2DS1, 3DL1, 3DL2, 3D33, 2DP1, 3DP1003

KIR – 2DL1, 2DL3, 2DL4, 2DS4, 3DL1, 3DL2, 3DL3, 2DP1, 3DP1003

EligibilityEligibility Age < 65Age < 65

– Autologous, mini-alloAutologous, mini-allo Age < 55Age < 55

– Myeloablative allogeneicMyeloablative allogeneic ExclusionsExclusions

– CHF, uncontrolled diabetes mellitus, CHF, uncontrolled diabetes mellitus, active infections, renal insufficiencyactive infections, renal insufficiency

Indications Autologous Indications Autologous TransplantTransplant Multiple myelomaMultiple myeloma NHLNHL Hodgkin’s diseaseHodgkin’s disease AMLAML NeuroblastomaNeuroblastoma Ovarian cancerOvarian cancer Germ-cell tumorsGerm-cell tumors

Autoimmune Autoimmune disordersdisorders

AmyloidosisAmyloidosis


Indications for Indications for Allogeneic TransplantAllogeneic Transplant AMLAML ALLALL CMLCML MDSMDS MPDMPD NHLNHL Hodgkin’s DiseaseHodgkin’s Disease CLLCLL Multiple myelomaMultiple myeloma Juvenile CMLJuvenile CML

Aplastic anemiaAplastic anemia PNHPNH Fanconi’s anemiaFanconi’s anemia Blackfan-DiamondBlackfan-Diamond Thalessemia majorThalessemia major Sickle cell anemiaSickle cell anemia SCIDSCID Wiskott-AldrichWiskott-Aldrich Inborn errors of Inborn errors of

metabolismmetabolism


Preparative RegimensPreparative Regimens MyeloablativeMyeloablative

– High doses of chemotherapy +/- High doses of chemotherapy +/- radiationradiation

– 3 goals3 goals Eliminate malignancyEliminate malignancy Immunosuppression to allow Immunosuppression to allow

engraftmentengraftment Decrease graft versus host effectsDecrease graft versus host effects



Myeloablative Myeloablative RegimensRegimens Myeloablative RegimensMyeloablative Regimens

– Most common regimensMost common regimens Cyclophosphamide/TBICyclophosphamide/TBI Busulfan/CyclophosphamideBusulfan/Cyclophosphamide

Stem cells are essential to restore Stem cells are essential to restore marrow functionmarrow function



Myeloablative Myeloablative RegimensRegimens Therapy is based on diseaseTherapy is based on disease Other drugsOther drugs

– Etoposide, BCNU, cytarabine, Etoposide, BCNU, cytarabine, melphalanmelphalan

Graft versus leukemia effects in Graft versus leukemia effects in allogeneic donorsallogeneic donors



Umbilical Cord BloodUmbilical Cord Blood 11stst UCB transplant 16 years ago UCB transplant 16 years ago

– Child with Fanconi’s anemiaChild with Fanconi’s anemia Cell dose is given per recipient weightCell dose is given per recipient weight

– Lower patient weights the high the cell Lower patient weights the high the cell dosedose

– 2 x 102 x 1077 nucleated cells/kg nucleated cells/kg– 1.7 x 101.7 x 1077 CD 34+ cells/kg CD 34+ cells/kg

4/6 match UCB with sufficient cells has 4/6 match UCB with sufficient cells has a similar outcome to a matched or one a similar outcome to a matched or one antigen mismatched MUDantigen mismatched MUD

Chao NJ, Emerson SG, Weinberg KI. Stem cell transplantation (Cord Blood Transplants). Am Soc Hematol Ed Book. 2004:354-371.

Umbilical Cord BloodUmbilical Cord Blood Umbilical Cord BloodUmbilical Cord Blood

– CryopreservedCryopreserved– Small number of stem cellsSmall number of stem cells– Higher incidence of engraftment Higher incidence of engraftment

failurefailure Using more than one unit in adultsUsing more than one unit in adults

– Lower risk of GVHDLower risk of GVHD– Degree of matching not as stringentDegree of matching not as stringent


Umbilical Cord BloodUmbilical Cord Blood Lower GVHDLower GVHD TRM not different than MUDTRM not different than MUD Can be used with myeloablative Can be used with myeloablative

or nonmyeloablative conditioning or nonmyeloablative conditioning (on a clinical trial)(on a clinical trial)


ComplicationsComplications EarlyEarly

– MucositisMucositis– Sinusoidal obstructive syndrome Sinusoidal obstructive syndrome

(VOD)(VOD) Fluid retention, jaundice, hepatomegalyFluid retention, jaundice, hepatomegaly

– Transplant related infectionsTransplant related infections Damage to mouth, gut and skinDamage to mouth, gut and skin Prolonged neutropeniaProlonged neutropenia



– PancytopeniaPancytopenia PRBC and platelet transfusionsPRBC and platelet transfusions Broad spectrum antimicrobialsBroad spectrum antimicrobials Antifungals if prolonged fevers 3-5 daysAntifungals if prolonged fevers 3-5 days



– Graft Versus Host DiseaseGraft Versus Host Disease Acute GVHD to day 100Acute GVHD to day 100

– Skin, GI tract, liverSkin, GI tract, liver



GVHDGVHD In GVH diseases donor-derived immuno-competent lymphocytes react In GVH diseases donor-derived immuno-competent lymphocytes react

with HLA incompatible recipient cells and induce inflammatory with HLA incompatible recipient cells and induce inflammatory responses in host tissues such as the skin and gastrointestinal tract. responses in host tissues such as the skin and gastrointestinal tract.

GVH disease seems more likely in cases whereby the donor is well GVH disease seems more likely in cases whereby the donor is well matched for the patient.matched for the patient.

Direct and indirect HLA allorecognition mediate GVH reactions if Direct and indirect HLA allorecognition mediate GVH reactions if immunocompetent donor cells recognize recipient incompatibilities.immunocompetent donor cells recognize recipient incompatibilities.

During infection, microbial antigens are processed by APC and During infection, microbial antigens are processed by APC and presented via HLA molecules to T-cells that elicit cytotoxic and DTH-presented via HLA molecules to T-cells that elicit cytotoxic and DTH-like inflammatory reactions in the allograft.like inflammatory reactions in the allograft.


– Graft RejectionGraft Rejection Host versus graftHost versus graft Drug injury to marrowDrug injury to marrow Viral infections: CMV, HHV-6 & 8Viral infections: CMV, HHV-6 & 8

– Interstitial PneumonitisInterstitial Pneumonitis Diffuse alveolar hemorrhageDiffuse alveolar hemorrhage Too few donor stem cellsToo few donor stem cells ARDS often caused by CMVARDS often caused by CMV


ComplicationsComplications DelayedDelayed

– Chronic GVHDChronic GVHD Scleroderma or Sjogrens syndromeScleroderma or Sjogrens syndrome BronchiolitisBronchiolitis KeratoconjunctivitisKeratoconjunctivitis MalabsorptionMalabsorption CholestasisCholestasis Esophageal strictureEsophageal stricture


Late ComplicationsLate Complications Secondary TumorsSecondary Tumors

– Acute leukemias, solid tumors, MDSAcute leukemias, solid tumors, MDS– Months to years after transplantMonths to years after transplant– Increased incidence with TBIIncreased incidence with TBI

Late InfectionsLate Infections– Bacterial, viral fungalBacterial, viral fungal– Months after transplantMonths after transplant– Associated with GVHDAssociated with GVHD– Need repeat vaccinationsNeed repeat vaccinations

Pneumovax, Hep B, Hemophilus influenza b, Pneumovax, Hep B, Hemophilus influenza b, poliovirus, diphtheria/tetanus, flupoliovirus, diphtheria/tetanus, flu


Human herpesvirus 6 infection in hematopoietic Human herpesvirus 6 infection in hematopoietic cell transplant recipientscell transplant recipients

Human herpesvirus 6 (HHV-6) is a member of the Roseolovirus genus of the beta-herpesvirus Human herpesvirus 6 (HHV-6) is a member of the Roseolovirus genus of the beta-herpesvirus subfamily of human herpesviruses. There are two HHV-6 variants, HHV-6A and HHV-6B. Based subfamily of human herpesviruses. There are two HHV-6 variants, HHV-6A and HHV-6B. Based on their distinctive biological properties and genome sequences, the Herpesvirales Study on their distinctive biological properties and genome sequences, the Herpesvirales Study Group of the International Committee on Taxonomy of Viruses has classified HHV-6A and Group of the International Committee on Taxonomy of Viruses has classified HHV-6A and HHV-6B as two distinct herpesvirus species.HHV-6B as two distinct herpesvirus species.

The vast majority of documented primary infections and reactivation events are due to HHV-The vast majority of documented primary infections and reactivation events are due to HHV-6B. HHV-6B infects most children within the first three years of life and, like other 6B. HHV-6B infects most children within the first three years of life and, like other herpesviruses, it establishes latency after primary infection. HHV-6B may reactivate in herpesviruses, it establishes latency after primary infection. HHV-6B may reactivate in immunocompromised hosts, especially following allogeneic hematopoietic cell transplantation immunocompromised hosts, especially following allogeneic hematopoietic cell transplantation (HCT). Encephalitis is the most clearly established clinical manifestation of HHV-6 reactivation (HCT). Encephalitis is the most clearly established clinical manifestation of HHV-6 reactivation in allogeneic HCT recipients, and may result in substantial morbidity. Little is known about the in allogeneic HCT recipients, and may result in substantial morbidity. Little is known about the epidemiology or clinical implications of HHV-6A.epidemiology or clinical implications of HHV-6A.

The epidemiology, clinical manifestations, diagnosis, and treatment of HHV-6 infections in The epidemiology, clinical manifestations, diagnosis, and treatment of HHV-6 infections in HCT recipients will be discussed here. HHV-6 infections in patients who are not HCT recipients HCT recipients will be discussed here. HHV-6 infections in patients who are not HCT recipients are presented separately. are presented separately.

EPIDEMIOLOGYEPIDEMIOLOGY Human herpesvirus 6 (HHV-6) reactivation occurs in 30 to 70 percent of patients undergoing Human herpesvirus 6 (HHV-6) reactivation occurs in 30 to 70 percent of patients undergoing

allogeneic hematopoietic cell transplantation (HCT) , with encephalitis occurring in only a allogeneic hematopoietic cell transplantation (HCT) , with encephalitis occurring in only a small subset of these patients. HHV-6 reactivation often manifests as HHV-6 viremia, and small subset of these patients. HHV-6 reactivation often manifests as HHV-6 viremia, and typically occurs between two and four weeks after transplantation. HHV-6B accounts for most typically occurs between two and four weeks after transplantation. HHV-6B accounts for most reactivations, with HHV-6A accounting for fewer than 3 percent of cases.reactivations, with HHV-6A accounting for fewer than 3 percent of cases.

Risk factorsRisk factors — Both demographic and clinical factors may influence the risk of HHV-6 — Both demographic and clinical factors may influence the risk of HHV-6 reactivation. As an example, recipients of allogeneic HCT are at higher risk of HHV-6 reactivation. As an example, recipients of allogeneic HCT are at higher risk of HHV-6 reactivation than recipients of autologous HCT; among allogeneic HCT recipients, those who reactivation than recipients of autologous HCT; among allogeneic HCT recipients, those who receive transplants from unrelated or HLA-mismatched donors are at particularly increased receive transplants from unrelated or HLA-mismatched donors are at particularly increased risk .risk .

Romanian BMR Romanian BMR Started in 2003Started in 2003 EFI Accredited in 2006EFI Accredited in 2006 Holds details of stem cell donors and cord Holds details of stem cell donors and cord

donations from Moldavia, Transilvania, donations from Moldavia, Transilvania, Banat, Black Sea Coast, Walachia.Banat, Black Sea Coast, Walachia.

We need to contiue to recruit more We need to contiue to recruit more donors, particularly from ethnic donors, particularly from ethnic communitiescommunities

HLA DNA 2 digits typed for HLA A, B, C, HLA DNA 2 digits typed for HLA A, B, C, DRB1 and DQB1DRB1 and DQB1

Lung transplantation, hand, Lung transplantation, hand, skin and corneal skin and corneal transplantationtransplantation

Prof. Ileana ConstantinescuProf. Ileana Constantinescu

Lung transplantationLung transplantation The influence of HLA in lung The influence of HLA in lung

transplantation is open to debate.transplantation is open to debate. Donated lungs are allocated on the whole Donated lungs are allocated on the whole

without consideration of HLA without consideration of HLA compatibility.compatibility.

Only when a potential recipient has been Only when a potential recipient has been found to be sensitized to predefined HLA found to be sensitized to predefined HLA specificities, is the donor HLA type used specificities, is the donor HLA type used to determine suitability.to determine suitability.

Requirements for potential donorsRequirements for potential donorsThere are certain requirements for potential lung donors, due to the needs of the potential recipient. In There are certain requirements for potential lung donors, due to the needs of the potential recipient. In

the case of living donors, this is also in consideration of how the surgery will affect the donor:the case of living donors, this is also in consideration of how the surgery will affect the donor: healthy;healthy; size match; the donated lung or lungs must be large enough to adequately oxygenate the patient, size match; the donated lung or lungs must be large enough to adequately oxygenate the patient,

but small enough to fit within the recipient's chest cavity;but small enough to fit within the recipient's chest cavity; age;age; blood type.blood type.

Requirements for potential recipientsRequirements for potential recipientsWhile a transplant center is free to set its own criteria for transplant candidates, certain requirements While a transplant center is free to set its own criteria for transplant candidates, certain requirements

are generally agreed upon:are generally agreed upon: end-stage lung disease;end-stage lung disease; has exhausted other available therapies without success;has exhausted other available therapies without success; no other chronic medical conditions (e.g. heart, kidney, liver);no other chronic medical conditions (e.g. heart, kidney, liver); no current infections or recent cancer. There are certain cases where pre-existing infection is no current infections or recent cancer. There are certain cases where pre-existing infection is

unavoidable, as with many patients with cystic fibrosis. In such cases, transplant centers, at their unavoidable, as with many patients with cystic fibrosis. In such cases, transplant centers, at their own discretion, may accept or reject patients with current infections of own discretion, may accept or reject patients with current infections of B virusB virus

no HIV or hepatitisno HIV or hepatitis no alcohol, smoking, or drug abuse;no alcohol, smoking, or drug abuse; within an acceptable weight range (marked undernourishment or obesity are both associated with within an acceptable weight range (marked undernourishment or obesity are both associated with

increased mortality);increased mortality); age age acceptable psychological profile;acceptable psychological profile; has social support system;has social support system; financially able to pay for expenses (where medical care is paid for directly by the patient);financially able to pay for expenses (where medical care is paid for directly by the patient); able to comply with post-transplant regimen. A lung transplant is a major operation, and following able to comply with post-transplant regimen. A lung transplant is a major operation, and following

the transplant, the patient must be willing to adhere to a lifetime regimen of medications as well as the transplant, the patient must be willing to adhere to a lifetime regimen of medications as well as continuing medical care.continuing medical care.

RisksRisks As with any surgical procedure, there are risks of bleeding and infection. The newly transplanted lung itself may fail to As with any surgical procedure, there are risks of bleeding and infection. The newly transplanted lung itself may fail to

properly heal and function. Because a large portion of the patient's body has been exposed to the outside air, sepsis is properly heal and function. Because a large portion of the patient's body has been exposed to the outside air, sepsis is a possibility, so antibiotics will be given to try to prevent that. Other complications include Post-transplant a possibility, so antibiotics will be given to try to prevent that. Other complications include Post-transplant lymphoproliferative disorder, a form of lymphoma due to the immune suppressants, and gastrointestinal inflammation lymphoproliferative disorder, a form of lymphoma due to the immune suppressants, and gastrointestinal inflammation and ulceration of the stomach and esophagus.and ulceration of the stomach and esophagus.

Transplant rejection is a primary concern, both immediately after the surgery and continuing throughout the patient's Transplant rejection is a primary concern, both immediately after the surgery and continuing throughout the patient's life. Because the transplanted lung or lungs come from another person, the recipient's immune system will "see" it as life. Because the transplanted lung or lungs come from another person, the recipient's immune system will "see" it as an invader and attempt to neutralize it. Transplant rejection is a serious condition and must be treated as soon as an invader and attempt to neutralize it. Transplant rejection is a serious condition and must be treated as soon as possible.possible.

Signs of rejection:Signs of rejection: fever;fever; flu-like symptoms, including chills, dizziness, nausea, general feeling of illness, night sweats;flu-like symptoms, including chills, dizziness, nausea, general feeling of illness, night sweats; increased difficulty in breathing;increased difficulty in breathing; worsening pulmonary test results;worsening pulmonary test results; increased chest pain or tenderness;increased chest pain or tenderness; increase or decrease in body weight of more than two kilograms in a 24-hour period.increase or decrease in body weight of more than two kilograms in a 24-hour period. In order to prevent transplant rejection and subsequent damage to the new lung or lungs, patients must take a regimen In order to prevent transplant rejection and subsequent damage to the new lung or lungs, patients must take a regimen

of immunosuppressive drugs. Patients will normally have to take a combination of these medicines in order to combat of immunosuppressive drugs. Patients will normally have to take a combination of these medicines in order to combat the risk of rejection. the risk of rejection.

This is a lifelong commitment, and must be strictly adhered to. The immunosuppressive regimen is begun just before or This is a lifelong commitment, and must be strictly adhered to. The immunosuppressive regimen is begun just before or after surgery. Usually the regimen includes cyclosporine, azathioprine and corticosteroids, but as episodes of rejection after surgery. Usually the regimen includes cyclosporine, azathioprine and corticosteroids, but as episodes of rejection may reoccur throughout a patient's life, the exact choices and dosages of immunosuppressants may have to be may reoccur throughout a patient's life, the exact choices and dosages of immunosuppressants may have to be modified over time. Sometimes tacrolimus is given instead of cyclosporine and mycophenolate mofetil instead of modified over time. Sometimes tacrolimus is given instead of cyclosporine and mycophenolate mofetil instead of azathioprine.azathioprine.

The immunosuppressants that are needed to prevent organ rejection also introduce some risks. By lowering the body's The immunosuppressants that are needed to prevent organ rejection also introduce some risks. By lowering the body's ability to mount an immune reaction, these medicines also increase the chances of infection. Antibiotics may be ability to mount an immune reaction, these medicines also increase the chances of infection. Antibiotics may be prescribed in order to treat or prevent such infections. In turn, infection may increase the risk of rejection, and prescribed in order to treat or prevent such infections. In turn, infection may increase the risk of rejection, and generally an interaction may prevail between both risks. Certain medications may also have nephrotoxic or other generally an interaction may prevail between both risks. Certain medications may also have nephrotoxic or other potentially harmful side-effects. Other medications may also be prescribed in order to help alleviate these side effects. potentially harmful side-effects. Other medications may also be prescribed in order to help alleviate these side effects. There is also the risk that a patient may have an allergic reaction to the medications. Close follow-up care is required in There is also the risk that a patient may have an allergic reaction to the medications. Close follow-up care is required in order to balance the benefits of these drugs versus their potential risks.order to balance the benefits of these drugs versus their potential risks.

Chronic rejection, meaning repeated bouts of rejection symptoms beyond the first year after the transplant surgery, Chronic rejection, meaning repeated bouts of rejection symptoms beyond the first year after the transplant surgery, occurs in approximately 50% of patients. Such chronic rejection presents itself as bronchiolitis obliterans, or less occurs in approximately 50% of patients. Such chronic rejection presents itself as bronchiolitis obliterans, or less frequently, atherosclerosis.frequently, atherosclerosis.

• The poorer outcome of lung transplants The poorer outcome of lung transplants compared to hearts is indicative of compared to hearts is indicative of additional risk factors that help to mask additional risk factors that help to mask other influences such as HLA.other influences such as HLA.

• There are cases with no HLA mismatch, There are cases with no HLA mismatch, but with time, more cases where few HLA but with time, more cases where few HLA mismatches exist are gradually added.mismatches exist are gradually added.

• HLA mismatches HLA mismatches have an influence on have an influence on acute rejection as well as on the acute rejection as well as on the development of bronchiolitis obliterans development of bronchiolitis obliterans syndrome.syndrome.

• HLA-DR mismatch HLA-DR mismatch is commonly is commonly recognized as having the greatest recognized as having the greatest influence.influence.

Tissue typingTissue typing ABO matchABO match Complete viral screeningComplete viral screening HLA A, HLA B and HLA DRB1HLA A, HLA B and HLA DRB1 PRA, crossmatchPRA, crossmatch TSH, T3, T4TSH, T3, T4 PTH, calcitonine osteocalcin, vit.D, PTH, calcitonine osteocalcin, vit.D,

biochemistry, tumor markers: CEA, CA biochemistry, tumor markers: CEA, CA 19-9, CA 125, AFP, 19-9, CA 125, AFP, ββ-HCG, -HCG, αα1-1-globulinaglobulina

PrognosisPrognosis1 year survival

5 years survival

10 years survival

Lung transplant

83.6% 53.4% 28.4%

Heart-lung transplant

73.8% 46.5% 28.3%

Skin transplantationSkin transplantation

Skin Skin transplantationtransplantation

The principles of managing patients with The principles of managing patients with severe burns involve the maitenance of severe burns involve the maitenance of body homeostasisbody homeostasis, , nitrogen balancenitrogen balance, , immunocompetenceimmunocompetence and the and the exclusion of exclusion of microorganism microorganism until nonviable tissue is until nonviable tissue is removed and the wound safely closed.removed and the wound safely closed.

If the function of skin is not restored in a If the function of skin is not restored in a few weeks, the patient will die as a result few weeks, the patient will die as a result of complex sequence of of complex sequence of metabolic metabolic abnormalities abnormalities and and septic complications.septic complications.

Skin transplantationSkin transplantation• In the absence of autologous skin, In the absence of autologous skin,

allograft skin (fresh human cadaveric allograft skin (fresh human cadaveric skin)skin) is the best biological membrane for is the best biological membrane for burn wound coverage.burn wound coverage.

• XenograftXenograft (porcine skin) – strong (porcine skin) – strong antigenity that leads to rapid rejection antigenity that leads to rapid rejection xenograft has to be removed on the xenograft has to be removed on the third day after application.third day after application.

• Human placental membranes Human placental membranes – accelerate – accelerate the healing process by exerting an the healing process by exerting an angiogenic effect and increasing capillary angiogenic effect and increasing capillary density of the underlying wound bed.density of the underlying wound bed.

Allograft skinAllograft skin• Used for temporary coverage of burn Used for temporary coverage of burn

wounds.wounds.• Rejection of the grafts inevitably occurs after Rejection of the grafts inevitably occurs after

2 weeks, 2 weeks, despite of depressed immunity.despite of depressed immunity.• Prolongation of the allograft skin survival to Prolongation of the allograft skin survival to

about about 6 weeks 6 weeks could be achieved by pre-could be achieved by pre-treating with treating with steroidssteroids and and UV light.UV light.

• The best match between donor and recipient The best match between donor and recipient is is identity for HLA-A, B and DRB1identity for HLA-A, B and DRB1. .

• The use of cyclosporine prolongs the skin The use of cyclosporine prolongs the skin graft survival, but the rejection occurs within graft survival, but the rejection occurs within 2 weeks after treatment is stopped.2 weeks after treatment is stopped.

Hand transplantationHand transplantation(composite tissue (composite tissue allotransplatation)allotransplatation)

Hand transplantationHand transplantation(composite tissue (composite tissue allotransplatation)allotransplatation)

A hand transplant, unlike a solid organ A hand transplant, unlike a solid organ transplant, involves transplant, involves multiple tissues multiple tissues (skin, (skin, muscle, tendon, bone, cartilage, fat, muscle, tendon, bone, cartilage, fat, nerves and blood vessels) and can be nerves and blood vessels) and can be considered the “gold standard” in CTA.considered the “gold standard” in CTA.

The world experience in human hand The world experience in human hand transplantation to date includes transplantation to date includes 50 50 transplants performed in 36 recipientstransplants performed in 36 recipients.. (www.handregistry.com)(www.handregistry.com)

Hand transplantationHand transplantation• The procedure is The procedure is for individuals who have for individuals who have

experienced the difficult loss of a hand or forearm experienced the difficult loss of a hand or forearm due to: (1) due to: (1) traumatrauma; (2) ; (2) life saving interventionslife saving interventions that that caused permanent injury to the hand or forearmcaused permanent injury to the hand or forearm..

• HHand transplant procedure and transplant procedure is is notnot being considered being considered forfor::

congenital anomaliescongenital anomalies loss of a limb due to cancerloss of a limb due to cancer leg amputations leg amputations individuals whose injury is limited to fingersindividuals whose injury is limited to fingers

Donated limbs would come from brain dead living Donated limbs would come from brain dead living donorsdonors..

Hand transplantationHand transplantation• TThe majority of patients demonstrated at least he majority of patients demonstrated at least

one episode of acute rejection in the first year, one episode of acute rejection in the first year, and thand thee skin was the primary target of the skin was the primary target of the immune responseimmune response..

• The high antigenicity of the skin can, in part, be The high antigenicity of the skin can, in part, be related to the high proportion of potent related to the high proportion of potent antigen-antigen-presenting cells (Langerhans cells)presenting cells (Langerhans cells) and and keratinocyteskeratinocytes that express major that express major histocompatibility complex (MHC) I histocompatibility complex (MHC) I constitutively, and MHC II, intercellular constitutively, and MHC II, intercellular adhesion molecule 1 (ICAM)-I and adhesion molecule 1 (ICAM)-I and proinflammatory cytokines upon stimulation. proinflammatory cytokines upon stimulation.

• VViral infections, in particular cytomegalovirus iral infections, in particular cytomegalovirus (CMV), have been postulated to trigger the (CMV), have been postulated to trigger the episodes of acute rejection episodes of acute rejection

Hand transplantationHand transplantation is a surgical procedure to transplant a hand from one human is a surgical procedure to transplant a hand from one human to another. The "donor" hand usually comes from a brain-dead donor and is transplanted to another. The "donor" hand usually comes from a brain-dead donor and is transplanted to a recipient who has lost one or both hands/arms. Most hand transplants to date have to a recipient who has lost one or both hands/arms. Most hand transplants to date have been performed on below elbow amputees, although above elbow transplants are gaining been performed on below elbow amputees, although above elbow transplants are gaining popularity. Hand transplants were the first of a new category of transplants where popularity. Hand transplants were the first of a new category of transplants where multiple organs are transplanted as a single functional unit, now termed "Vascularized multiple organs are transplanted as a single functional unit, now termed "Vascularized Composite Allotransplantation" or VCA.Composite Allotransplantation" or VCA.

The operation is quite extensive and typically lasts from 8–12 hours. By comparison, a The operation is quite extensive and typically lasts from 8–12 hours. By comparison, a typical head transplantoperation lasts 6 to 8 hours. Surgeons usually connect the bones typical head transplantoperation lasts 6 to 8 hours. Surgeons usually connect the bones first, followed by tendons, arteries, nerves, veins, and skin.first, followed by tendons, arteries, nerves, veins, and skin.

The recipient of a hand transplant needs to take immunosuppressive drugs similar to The recipient of a hand transplant needs to take immunosuppressive drugs similar to other transplants such as kidneys or livers, as the body's natural immune system will try other transplants such as kidneys or livers, as the body's natural immune system will try to reject, or destroy, the hand. These drugs cause the recipient to have a weaker immune to reject, or destroy, the hand. These drugs cause the recipient to have a weaker immune system which may lead to an increased risk of infections and some cancers. There have system which may lead to an increased risk of infections and some cancers. There have been many advances in solid organ transplantation over the years that have made these been many advances in solid organ transplantation over the years that have made these medications quite tolerable.medications quite tolerable.

After the transplant, there is a period of extensive hand therapy/rehabilitation which After the transplant, there is a period of extensive hand therapy/rehabilitation which helps the recipients regain function of the transplanted hand. Those patients who are helps the recipients regain function of the transplanted hand. Those patients who are dedicated to taking the medications and performing the physical therapy following a dedicated to taking the medications and performing the physical therapy following a hand transplant have had remarkable success in regaining function of the new hand transplant have had remarkable success in regaining function of the new hands/arms.hands/arms.

Corneal Corneal transplantationtransplantation

Types of Cornea Types of Cornea TransplantsTransplants

The cornea contains five layers. Cornea transplants don't always The cornea contains five layers. Cornea transplants don't always transfer all the layers.transfer all the layers.

Types of cornea transplants include:Types of cornea transplants include: Penetrating (full thickness) cornea transplant.Penetrating (full thickness) cornea transplant. This involves This involves

transplanting all the layers of the cornea from the donor.transplanting all the layers of the cornea from the donor. Lamellar cornea transplantLamellar cornea transplant. . During this procedure, the surgeon only During this procedure, the surgeon only

replaces some of the layers of the cornea with the transplant.replaces some of the layers of the cornea with the transplant. In a lamellar cornea transplant, selected layers are transplanted, which In a lamellar cornea transplant, selected layers are transplanted, which

can include the deepest layer, called the endothelium (posterior can include the deepest layer, called the endothelium (posterior lamellar cornea transplant). Commonly performed versions of this lamellar cornea transplant). Commonly performed versions of this procedure include Descemet's Stripping Automated Endothelial procedure include Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK) or Descemet's Membrane Endothelial Keratoplasty (DSAEK) or Descemet's Membrane Endothelial Keratoplasty (DMEK).Keratoplasty (DMEK).

Or it can include layers closer to the surface (anterior lamellar cornea Or it can include layers closer to the surface (anterior lamellar cornea transplant).transplant).

Lamellar transplants may be more appropriate than full penetrating Lamellar transplants may be more appropriate than full penetrating transplants when the disease process is limited to only a portion of the transplants when the disease process is limited to only a portion of the cornea.cornea.

Corneal transplantationCorneal transplantation It is estimated that 10.000.000 people It is estimated that 10.000.000 people

are affected by various disorders that are affected by various disorders that would benefit from corneal would benefit from corneal transplantation.transplantation.

100.000 procedures are performed 100.000 procedures are performed worldwide each year.worldwide each year.

–UK: >2300 grafts/yrUK: >2300 grafts/yr–Australia: 1500 grafts/yrAustralia: 1500 grafts/yr–USA: > 40.000 people are USA: > 40.000 people are corneal transplantedcorneal transplanted

Corneal transplantationCorneal transplantationIndications:Indications: Bullous keratopathyBullous keratopathy Corneal degenerationCorneal degeneration Corneal perforationCorneal perforation Keratoglobus and dystrophyKeratoglobus and dystrophy Scarring due to keratitis and traumaScarring due to keratitis and trauma Inflamed corneal tissue unresponsive Inflamed corneal tissue unresponsive

to antibiotics or anti-viral treatmentto antibiotics or anti-viral treatment

IndicationsIndicationsIndications for include the following:Indications for include the following: Optical: Optical: To improve visual acuity by replacing the opaque or distorted host tissue by clear To improve visual acuity by replacing the opaque or distorted host tissue by clear

healthy donor tissue. The most common indication in this category is pseudophakic bullous healthy donor tissue. The most common indication in this category is pseudophakic bullous keratopathy, followed by keratoconus, corneal degeneration, keratoglobus and dystrophy, as keratopathy, followed by keratoconus, corneal degeneration, keratoglobus and dystrophy, as well as scarring due to keratitis and trauma.well as scarring due to keratitis and trauma.

Tectonic/reconstructive: Tectonic/reconstructive: To preserve corneal anatomy and integrity in patients with stromal To preserve corneal anatomy and integrity in patients with stromal thinning and descemetoceles, or to reconstruct the anatomy of the eye, e.g. after corneal thinning and descemetoceles, or to reconstruct the anatomy of the eye, e.g. after corneal perforation.perforation.

Therapeutic: Therapeutic: To remove inflamed corneal tissue unresponsive to treatment by antibiotics or To remove inflamed corneal tissue unresponsive to treatment by antibiotics or anti-virals.anti-virals.

Cosmetic: Cosmetic: To improve the appearance of patients with corneal scars that have given a whitish To improve the appearance of patients with corneal scars that have given a whitish or opaque hue to the cornea.or opaque hue to the cornea.

Pre-operative examinationPre-operative examination In most instances, the patient will meet with their ophthalmologist for an examination in the In most instances, the patient will meet with their ophthalmologist for an examination in the

weeks or months preceding the surgery. During the exam, the ophthalmologist will examine weeks or months preceding the surgery. During the exam, the ophthalmologist will examine the eye and diagnose the condition. The doctor will then discuss the condition with the the eye and diagnose the condition. The doctor will then discuss the condition with the patient, including the different treatment options available. The doctor will also discuss the patient, including the different treatment options available. The doctor will also discuss the risks and benefits of the various options. If the patient elects to proceed with the surgery, the risks and benefits of the various options. If the patient elects to proceed with the surgery, the doctor will have the patient sign an informed consent form. The doctor might also perform a doctor will have the patient sign an informed consent form. The doctor might also perform a physical examination and order lab tests, such as blood work, X-rays, or an EKG.physical examination and order lab tests, such as blood work, X-rays, or an EKG.

The surgery date and time will also be set, and the patient will be told where the surgery will The surgery date and time will also be set, and the patient will be told where the surgery will take place. Within the United States, the supply of corneas is sufficient to meet the demand take place. Within the United States, the supply of corneas is sufficient to meet the demand for surgery and research purposes. Therefore, unlike other tissues for transplantation, delays for surgery and research purposes. Therefore, unlike other tissues for transplantation, delays and shortages are not an issue.and shortages are not an issue.

Corneal transplantationCorneal transplantation• HLA-A and HLA-B HLA-A and HLA-B antigens have been antigens have been

identified on identified on corneal epithelium, stromal corneal epithelium, stromal cells, corneal endothelial cellscells, corneal endothelial cells and are and are targets for CD8+ cytotoxic T cells.targets for CD8+ cytotoxic T cells.

• HLA-A and HLA-B matching HLA-A and HLA-B matching was associated was associated with with improved outcome of corneal graft improved outcome of corneal graft survival survival in high risk recipients.in high risk recipients.

• HLA-DRHLA-DR antigens are carried on antigens are carried on Langerhans Langerhans cellscells..

• The role of HLA-DR matching in corneal The role of HLA-DR matching in corneal transplantation remains controversial.transplantation remains controversial.

• ABO incompatibility would lead to late ABO incompatibility would lead to late corneal cloudingcorneal clouding

Corneal transplantationCorneal transplantationRisks:Risks: InfectionInfection – the cornea has no blood vessels – the cornea has no blood vessels

and it heals much more slowly.and it heals much more slowly. Graft failure Graft failure – can occur at any time, even – can occur at any time, even

years or decades later.years or decades later.

The role of HLA matching in reducing The role of HLA matching in reducing corneal graft failure could not be corneal graft failure could not be confirmed by all studies.confirmed by all studies.

< 10% of primary grafts undergo immune < 10% of primary grafts undergo immune rejection despite no routine HLA matching.rejection despite no routine HLA matching.

RisksRisks The risks are similar to other intraocular procedures, detachment or The risks are similar to other intraocular procedures, detachment or

displacement of lamellar transplants.displacement of lamellar transplants. There is also a risk of infection. Since the cornea has no blood vessels (it There is also a risk of infection. Since the cornea has no blood vessels (it

takes its nutrients from the aqueous humor) it heals much more slowly takes its nutrients from the aqueous humor) it heals much more slowly than a cut on the skin. While the wound is healing, it is possible that it than a cut on the skin. While the wound is healing, it is possible that it might become infected by various microorganisms.This risk is minimized might become infected by various microorganisms.This risk is minimized by antibiotic prophylaxis (using antibiotic eyedrops, even when no infection by antibiotic prophylaxis (using antibiotic eyedrops, even when no infection exists).exists).

There is a risk of cornea rejection, which occurs in about 20% of cases.There is a risk of cornea rejection, which occurs in about 20% of cases.

PrognosisPrognosis The prognosis for visual restoration and maintenance of ocular health with The prognosis for visual restoration and maintenance of ocular health with

corneal transplants is generally very good. Risks for failure or guarded corneal transplants is generally very good. Risks for failure or guarded prognoses are multifactorial. The type of transplant, the disease state prognoses are multifactorial. The type of transplant, the disease state requiring the procedure, the health of the other parts of the recipient eye requiring the procedure, the health of the other parts of the recipient eye and even the health of the donor tissue may all confer a more or less and even the health of the donor tissue may all confer a more or less favorable prognosis.favorable prognosis.

The majority of corneal transplants result in significant improvement in The majority of corneal transplants result in significant improvement in visual function for many years or a lifetime. In cases of rejection or visual function for many years or a lifetime. In cases of rejection or transplant failure, the surgery generally can be repeated.transplant failure, the surgery generally can be repeated.

Recovery From a Cornea TransplantRecovery From a Cornea Transplant The risks of complications vary depending on how many layers of the cornea are The risks of complications vary depending on how many layers of the cornea are transplanted. The cornea is “immunologically privileged” so that no matching of donor to transplanted. The cornea is “immunologically privileged” so that no matching of donor to recipient is required. Additionally, steroid eye drops afford protection against rejection so recipient is required. Additionally, steroid eye drops afford protection against rejection so that pills and systemic medications are not required to prevent rejection. Y our body is that pills and systemic medications are not required to prevent rejection. Y our body is even less likely to reject the transplant if only the outer layers are used, compared to using even less likely to reject the transplant if only the outer layers are used, compared to using all the layers or the deepest layer. Rejection happens in less than 20% of cases overall.all the layers or the deepest layer. Rejection happens in less than 20% of cases overall.

Other problems can include:Other problems can include: Bleeding (rare)Bleeding (rare) ScarringScarring Cataract formation, retinal detachment, and damage to other parts of the eyeCataract formation, retinal detachment, and damage to other parts of the eye Leakage of fluid from the transplant incisionLeakage of fluid from the transplant incision Infection (rare)Infection (rare) Vision problems. Full thickness transplants can heal with large amounts of astigmatism, Vision problems. Full thickness transplants can heal with large amounts of astigmatism,

nearsightedness and farsightedness, requiring thick lenses on eyeglasses or contact nearsightedness and farsightedness, requiring thick lenses on eyeglasses or contact lenses.lenses.

In addition, some ailments that damage people's original cornea can also harm the new In addition, some ailments that damage people's original cornea can also harm the new cornea. For example, there is the possibility of recurrence of herpes simplex infection in cornea. For example, there is the possibility of recurrence of herpes simplex infection in the transplant.the transplant.

Rejection may even occur years after the surgery. If you notice any of these signs that last Rejection may even occur years after the surgery. If you notice any of these signs that last for more than six hours, call your eye doctor promptly. The doctor can give you medicine for more than six hours, call your eye doctor promptly. The doctor can give you medicine that can help prevent as well as treat rejection.that can help prevent as well as treat rejection.

Success Rates of Cornea Success Rates of Cornea TransplantsTransplants

Experts know more about the long-term success rates of Experts know more about the long-term success rates of penetrating cornea transplants, which use all the layers of the penetrating cornea transplants, which use all the layers of the cornea.cornea.

Success rates are also affected by the problem that needed to be Success rates are also affected by the problem that needed to be fixed with the transplant.fixed with the transplant.

For example, research has found that the new cornea lasts for at For example, research has found that the new cornea lasts for at least 10 years in:least 10 years in:

89% of people with keratoconus89% of people with keratoconus 73% of people with Fuchs' dystrophy73% of people with Fuchs' dystrophy 60% to 70% of people with corneal scarring60% to 70% of people with corneal scarring

curs 3,4, 5 imunologia transplantului

Documents