Organ Transplantation Dr. Nelson L. Rhodus Director of Oral Medicine University of Minnesota

Organ TransplantationOrgan Transplantation

Dr. Nelson L. RhodusDr. Nelson L. Rhodus

Director of Oral MedicineDirector of Oral Medicine

University of MinnesotaUniversity of Minnesota


Bone Marrow ( stem cell)Bone Marrow ( stem cell) Solid organsSolid organs

– HeartHeart

– LungLung

– LiverLiver

– KidneyKidney

– PancreasPancreas

– Small intestineSmall intestine


Heart transplantsHeart transplants First performed in 1967; first year only First performed in 1967; first year only

1:5 survived1:5 survived 2000= 3500 performed2000= 3500 performed Total= 53,000Total= 53,000 Present survival rate >70%Present survival rate >70%


KidneyKidney First solid organ transplant ( 1954) First solid organ transplant ( 1954)

performedperformed Since then >490,000 kidney transplantsSince then >490,000 kidney transplants Presently 581 centers perform >10,000 Presently 581 centers perform >10,000

kidney transplants per year: 1-year kidney transplants per year: 1-year survival rate >90%( cadaver~80%) survival rate >90%( cadaver~80%)

( 5 yr. ~70%)


Liver transplantsLiver transplants First liver transplant in 1967First liver transplant in 1967 >90,000 liver transplants>90,000 liver transplants > 8,000 liver transplants per year> 8,000 liver transplants per year 1-1-

year survival rate >90% year survival rate >90% ( 5 yr. ~70%)


Pancreas transplantsPancreas transplants first pancreas transplant was performed in

1966, by Kelly and Lillehei at the University of Minnesota

2000 >3500 transplants performed >2000 at the U of M ! 1 year survival rate >85% ( 5 yr. ~70%) survival rate w/o pancreas transplant = about

the same ! ( JAMA- Dec. ‘03)


Heart - lung transplantsHeart - lung transplants ~ 800 performed as of 2000~ 800 performed as of 2000 1 year survival ~ 60 %1 year survival ~ 60 %


Small intestine transplantsSmall intestine transplants less than 50 performed (some

combined with liver transplants) four transplant centers (Cambridge;

London, Ontario; Pittsburgh, and Omaha).

current 1-year survival rate at 70%.1

Bone marrow transplantationBone marrow transplantation

First performed in 1958First performed in 1958 Early = very poor prognosisEarly = very poor prognosis Immunosuppression, GVHD, rejectionImmunosuppression, GVHD, rejection 2000 > 100,0002000 > 100,000 Today = successful ( 50-80% survival Today = successful ( 50-80% survival

rate-1 year)rate-1 year)


HEART TRANSPLANTSHEART TRANSPLANTS Reasons; cardiomyopathy, congenital Reasons; cardiomyopathy, congenital

heart disease, atherosclerotic coronary heart disease, atherosclerotic coronary artery diseaseartery disease

Terminal heart disease (6-12 months)Terminal heart disease (6-12 months) Age <50-55 yearsAge <50-55 years


HEART TRANSPLANTSHEART TRANSPLANTS Good renal and hepatic functionGood renal and hepatic function No infectionsNo infections No diabetesNo diabetes Family supportFamily support


HEART TRANSPLANTSHEART TRANSPLANTS Causes of death:Causes of death: InfectionInfection 40%40% Acute graft rejectionAcute graft rejection 25%25% Chronic graft rejectionChronic graft rejection 10 %10 % Cardiac diseaseCardiac disease 25%25%


HEART TRANSPLANTSHEART TRANSPLANTS Endocarditis preventionEndocarditis prevention Pacemakers-arrhythmiasPacemakers-arrhythmias Medications- drugsMedications- drugs Avoid epinephrineAvoid epinephrine AnticoagulationAnticoagulation


HEART TRANSPLANTSHEART TRANSPLANTS ImmunosuppressionImmunosuppression Adrenal suppressionAdrenal suppression BleedingBleeding Infection (IE)Infection (IE)


HEART TRANSPLANTSHEART TRANSPLANTS ACCELERATED GRAFT ACCELERATED GRAFT

ATHEROSCLEROSIS(AGAS)ATHEROSCLEROSIS(AGAS) ~ 50 % of post-transplant patients have~ 50 % of post-transplant patients have

AGASAGAS( same degree as pre-( same degree as pre-

transplant)transplant)


HEART TRANSPLANTSHEART TRANSPLANTS Transplanted heart has no nerve supplyTransplanted heart has no nerve supply Therefore with AGAS there is NO Therefore with AGAS there is NO

ANGINA. MI will cause sudden death.ANGINA. MI will cause sudden death.


LIVER TRANSPLANTATIONLIVER TRANSPLANTATION Indications:Indications: Chronic active hepatitisChronic active hepatitis Extrahepatic biliary atresiaExtrahepatic biliary atresia Primary biliary cirrhosisPrimary biliary cirrhosis Budd-Chiari syndromeBudd-Chiari syndrome(hepatic vein thrombosis)(hepatic vein thrombosis)

Sclerosing cholangitisSclerosing cholangitis Hepatocellular carcinomaHepatocellular carcinoma


LIVER TRANSPLANTATIONLIVER TRANSPLANTATION Primary organ disease problemsPrimary organ disease problems Excessive bleedingExcessive bleeding InfectionInfection Altered drug metabolismAltered drug metabolism

HypertensionHypertension


RENAL TRANSPLANTATIONRENAL TRANSPLANTATION ESRD managementESRD management Endocarditis, endarteritisEndocarditis, endarteritis Same as other organ transplantsSame as other organ transplants Aggessive prevention-treatment of Aggessive prevention-treatment of

infectionsinfections Viral infections( CMV, HBV,HCV, HIV)Viral infections( CMV, HBV,HCV, HIV)


RENAL TRANSPLANTATIONRENAL TRANSPLANTATION Avoid certain drugsAvoid certain drugs( acetaminophen, ( acetaminophen,

phenacetin, tetracycline, phenacetin, tetracycline, aminoglycosides, ASA, K+, PCN, aminoglycosides, ASA, K+, PCN, Magnesium-antacids, etc.)Magnesium-antacids, etc.)

Laboratory tests: urinalysis( BUN, Laboratory tests: urinalysis( BUN, creatinine, protein, electrolytes)creatinine, protein, electrolytes)


conditioncondition success ratesuccess rate ALLALL 20-25%20-25% AMLAML 40-60%40-60% CMLCML 60%60% Aplastic anemiaAplastic anemia 20-25%20-25% LymphomaLymphoma 25-40%25-40% NeuroblastomaNeuroblastoma 20-30%20-30%


HISTOCOMPATABILITYHISTOCOMPATABILITY AutologousAutologous selfself 30-50%30-50% AllogeneicAllogeneic siblingsibling 15-25%15-25% SyngeneicSyngeneic ident. twinident. twin < 5%< 5% HaploidenticalHaploidentical parentparent < 5%< 5% UnrelatedUnrelated any donorany donor 25-30%25-30%


Stages:Stages: Medical evaluationMedical evaluation 1 week1 week Histocompatibility matchingHistocompatibility matching 1 day1 day BM procurement (iliac crest)BM procurement (iliac crest) 1-2 weeks1-2 weeks Immunosuppressive Tx (TBI)1-2 weeksImmunosuppressive Tx (TBI)1-2 weeks Pancytopenic phasePancytopenic phase 4-6 weeks4-6 weeks Immune recovery phaseImmune recovery phase 1 year1 year Long-term recoveryLong-term recovery 1-4 years1-4 years


Three phases of immunosuppressive TxThree phases of immunosuppressive Tx 1.) pre-transplant1.) pre-transplant Cyclophosphimide or methotrexateCyclophosphimide or methotrexate

± TBI ( single or fractionated)± TBI ( single or fractionated) 2.) transplant( pancytopenic phase)2.) transplant( pancytopenic phase) 3.) cyclosporine, methotrexate, IFN-a3.) cyclosporine, methotrexate, IFN-a

to prevent GVHD to prevent GVHD


Phases 2-3 pancytopenic phasePhases 2-3 pancytopenic phase ANC<500: severe susceptibility to ANC<500: severe susceptibility to

infection : 4-6 weeks post-transplantinfection : 4-6 weeks post-transplant Immunosuppression ( long-term)Immunosuppression ( long-term) Recurrence of leukemiaRecurrence of leukemia

GVHDGVHD encephalitisencephalitis


ORAL COMPLICATIONSORAL COMPLICATIONS Peak 2-3 weeks post BMTPeak 2-3 weeks post BMT ( pancytopenic phase: ANC<500)( pancytopenic phase: ANC<500) Mucositis, xerostomia, GVHD, viral Mucositis, xerostomia, GVHD, viral

infectionsinfections(HSV,HIV),(HSV,HIV), ELP-like, ELP-like,

erythema, erythema, CandidiasisCandidiasis

Dental management of the Dental management of the Organ Transplant patientOrgan Transplant patient

Dr. Nelson L. RhodusDr. Nelson L. Rhodus

Director of Oral MedicineDirector of Oral Medicine

University of MinnesotaUniversity of Minnesota


Before transplantBefore transplant MEDICAL CONSULTATIONMEDICAL CONSULTATION Establish patient statusEstablish patient status primary organ failure-complicationsprimary organ failure-complications Current treatment-drugs, etc.Current treatment-drugs, etc. Antibiotic prophylaxisAntibiotic prophylaxis


LABORATORY TESTSLABORATORY TESTS CBCCBC differential white countdifferential white count plateletsplatelets PT, PTT, BTPT, PTT, BT


COMPLICATIONSCOMPLICATIONS Over-immunosuppressionOver-immunosuppression Side-effects of drugsSide-effects of drugs Rejection of transplantRejection of transplant

– AcuteAcute– ChronicChronic


DENTAL EVALUATIONDENTAL EVALUATION Aggressive treatment prior to Aggressive treatment prior to

immunosuppressionimmunosuppression Extract teeth with poor prognosisExtract teeth with poor prognosis Advanced perio, endo, questionableAdvanced perio, endo, questionable Aggressive oral hygiene: maintenanceAggressive oral hygiene: maintenance


IMMUNOSUPPRESSIONIMMUNOSUPPRESSION PrednisonePrednisone Aziothioprine(Immuran)Aziothioprine(Immuran) 33%*33%* CyclosporineCyclosporine 72%*72%* Antilymphocyte globulin (ALG)Antilymphocyte globulin (ALG)84%*84%*

* 1 year survival rate* 1 year survival rate


IMMUNOSUPPRESSIONIMMUNOSUPPRESSION InfectionInfection Delayed wound healingDelayed wound healing BleedingBleeding HypertensionHypertension Heart failureHeart failure Diabetes mellitusDiabetes mellitus


IMMUNOSUPPRESSIONIMMUNOSUPPRESSION Tumors ( lip cancer, lymphoma)Tumors ( lip cancer, lymphoma) Adrenal crisisAdrenal crisis AnemiaAnemia OsteoporosisOsteoporosis GI problemsGI problems


DENTAL MANAGEMENTDENTAL MANAGEMENT MEDICAL CONSULTATIONMEDICAL CONSULTATION Minimize stress, short appointmentsMinimize stress, short appointments Monitor vitals ( HTN)Monitor vitals ( HTN) Infections( endocarditis, endarteritis)Infections( endocarditis, endarteritis) Pneumonia, encephalitisPneumonia, encephalitis Aggessive prevention & Tx of infectionAggessive prevention & Tx of infection


DENTAL MANAGEMENTDENTAL MANAGEMENT BleedingBleeding GI problemsGI problems IMMUNOSUPPRESSIONIMMUNOSUPPRESSION Consider steroid supplementationConsider steroid supplementation Personal Oral hygienePersonal Oral hygiene

TransplantationTransplantation

ORAL COMPLICATIONSORAL COMPLICATIONS Bleeding, infections, poor wound Bleeding, infections, poor wound

healinghealing PainPain Mucositis, ulcers, xerostomia, Mucositis, ulcers, xerostomia,

dysguesia, dysphagiadysguesia, dysphagia


Tumors Tumors Lip carcinomaLip carcinoma 8-10%8-10% Kaposi’sKaposi’s 6-7 %6-7 % LymphomaLymphoma 20 %20 % Kidney CaKidney Ca 5 % 5 %


IMMUNOSUPPRESSIONIMMUNOSUPPRESSION Minor complicationsMinor complications Gingival hyperplasiaGingival hyperplasia HirsutismHirsutism GynecomastiaGynecomastia DepressionDepression


Graft rejectionGraft rejection Heart- death, retransplant( unlikely)Heart- death, retransplant( unlikely) Kidney- death, Kidney- death, HemodialysisHemodialysis, re-Tx, re-Tx Pancreas- death, insulin, re-TxPancreas- death, insulin, re-Tx


IMMEDIATE POST-TRANSPLANTIMMEDIATE POST-TRANSPLANT No routine dental treatment ~ 6 mos.No routine dental treatment ~ 6 mos. POHPOH Emergency( conservative) treatmentEmergency( conservative) treatment MEDICAL CONSULTATIONMEDICAL CONSULTATION


Stable graft period ( >6 months)Stable graft period ( >6 months) Most dental treatment can be performed Most dental treatment can be performed

with adequate managementwith adequate management OVER-IMMUNOSUPPRESSIONOVER-IMMUNOSUPPRESSION GVHDGVHD HTN, BLEEDING, DRUGS, etc.HTN, BLEEDING, DRUGS, etc. OTHER INFECTIONSOTHER INFECTIONS


CHRONIC REJECTION PERIODCHRONIC REJECTION PERIOD No routine dental treatment No routine dental treatment POHPOH Emergency( conservative) treatmentEmergency( conservative) treatment MEDICAL CONSULTATIONMEDICAL CONSULTATION


Salivary gland dysfunctionSalivary gland dysfunction Very aggressive oral hygiene programVery aggressive oral hygiene program POH: plaque control : toothbrushing, POH: plaque control : toothbrushing,

flossing, fluoridesflossing, fluorides Dietary counselingDietary counseling Perio treatmentPerio treatment Chlorohexidine gluconateChlorohexidine gluconate

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Organ Transplantation Dr. Nelson L. Rhodus Director of Oral Medicine University of Minnesota