Curs 6, 7, 8 Imunologia Transplantului

8/18/2019 Curs 6, 7, 8 Imunologia Transplantului

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• Prof. Ileana Constantinescu

Immunosuppression



Immunosuppression

Immunosuppressive protocols intransplantation include the targeting of

IL-2/IL-2R axis that are considered to bethe most important pathway for T–cellproliferation.



Immunosuppressantsclassifcation•Calcineurin inhibitors:

Cyclosporine, Tacrolimus•Antimetabolites:

Mycophenolat mofetil,

Aathioprine•Corticosteroids

•Prolieration inhibitors !mT"#inhibitors$mammalian target of rapamycin%&

'irolimus, (verolimus



The consideration of the various factors a)ecting transplant

outcome now turns to a discussion of a sub*ect of tremendousimportance not only to recipient selection but also to longtermtransplant recipient care and management, namely the issueof often associated immunosuppression.

'ince grat reection is provo+ed by an undesirable buthealthy immune response on the part of the host, it is

imperative for favorable transplant outcome that thetransplant recipient be in some way immunosuppressed. Immunosuppression of the transplant recipient falls into one

of two categories, either suppression targeted specicallytoward donor antigen or targeted nonspecically, resulting inbroader immunocompromise of the transplant recipient. Means

of achieving both antigen-nonspecic and specicimmunosuppression. Total lymphoid irradiation, while infreuently used today,

e)ectively eliminates the host immune response, resulting ingraft survival, albeit profound immunosuppression.

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More freuent approaches to cripple the transplantrecipient1s immune system have included the use of anti-lymphocyte globulins, such as $'(-)* directed against

T cell-mediated responses. C+) component of thehuman ( cell receptor, antimetabolite drugs* such asa,athioprine, inhibit nucleotide synthesis and result insuppressing the proliferative capacity of rapidly dividingcells, such as lymphocytes recently recruited to participatein an immune response.

'uch drugs are freuently used in combination withsteroids, such as prednisone* which is broadlyimmunosuppressive by inhibiting lymphocyte function, aswell as a drugs called Cyclosporine A or Tacrolimus

(FK506) which more specically inhibits T cell e2pressionof cyto+ine e)ector molecules. A triple regimen consistingof aathioprine, prednisone, and cyclosporine A iscommonly used post-transplant to manage heart and+idney transplant recipients.

3



'uch e)ective immunosuppressive measures, due to theirbroad impact on the host1s immune system, as well as freuentadverse side e)ects, have raised the issue of identifying meansof suppressing the transplant re*ection response in a more

antigen-specifc a.. It is hoped that such antigen-specicmeans of immunosuppression, though still in their infancy, willimpact less on the host1s immune system and result in fewerside e)ects associated with multiple drug use.

"ne strategy considered in antigen-specicimmunosuppression is to employ antibodies directed againstgrat antigens* such as !C alloantigens, which results in aprolongation of graft survival +nown as enhancement .

The mechanism by which anti-graft antibodies promotetransplant survival is currently under investigation. Anotherdonor antigen-specic approach to immunsuppression, still in

an e2perimental phase of study, is the use of anti-T cellreceptor (TC) antibodies to bloc+ host T cells specic forallogeneic M4C.



This +ind of therapy implies a detailed +nowledge notonly of which M4C alloantigens are e2pressed on eachgraft, but also which antigen epitopes are critical for

generating host T cell help during the alloimmuneresponse.

Antibody therapy, whether donor antigen-specic ornonspecic, due to its passive nature, usually reuireschronic administration. Associated with long-termantibody therapy is the adverse sensitiation of theindividual receiving these antibodies, which are usuallyraised in nonhuman species.

These antibodies, therefore, act as alloantigens due toforeign isotope seuences and as such have thepotential to provo+e anti-antibody responses in therecipient. Clearly, such a situation renders antibodytherapy of limited longterm value.

5



• In the face of these therapeutic di6culties, an appealing strategyaimed at inducing donor antigen specic immunosuppression is theconcept of tolerance! dened here as specic, acuired, longlasting immunological unresponsiveness. Tolerance to self antigens

occurs very early in life, during fetal and neonatal development.'elf-tolerance or central tolerance is principally acuired bynegative selection or elimination of potentially self-reactive T cellclones during thymic development. 7egative selection in thethymus is characteried by programmed cell death in a processreferred to as clonal deletion.

• (olerance to prospecti0e donor alloantigens, however, raisesthe issue of how to achieve tolerance in the adult transplantrecipient long after central or self-tolerance has been achieved.Issues surrounding how to establish peripheral 1nonth.mic

tolerance form the basis of many e2perimental studies in the eldsof transplantation and autoimmunity today. 8hile still at theirinception, these studies aim to elucidate how prior oral orintravenous administration of donor allo M4C antigens, in the caseof transplantation, sometimes achieves a tolerant state in thetransplant recipient.

9:



Also under investigation are the doses of antigen reuiredto induce tolerance, described as either lo" #one or high

#one, depending upon the relative doses of antigen needed

to achieve it. #oute of administration and antigen doseaside, e2perimental observations published to date haveindicated that tolerance to donor allo !C antigensma. be established b. a combination o acti0esuppression o the recipient immune response

and/or ailure to respond to oreign antigenmediated b. either ( cell clonal deletion or anergy.

Anergy may be dened as the absence of an immuneresponse due to loss of cell function or ;immune paralysis;

and may be reversible. <uture transplant therapy awaitsclarication of these issues.



Immunosupression

• Cyclosporin A& M(IA A2sym$T=2,

4P>C• Tacrolimus& M(IA IM2, 4P>C

• 'irolimus& M(IA IM2, 4P>C

• Methotre2at& M(IA T=2



Sadimmun. Concentrate for I.v. infusion

Immunosuppressive agent

Composition

Active component Sandimmun Neoral Sandimmun Neoral Sandimmun

1 soft gelatin capsule oral solution concentrate

for I.v.infusion

Ciclosporin 10 mg; 25 mg 100 mg/mL 50 mg/mL

50 mg; 100 mg

Sandimmun Neoral is a ne p!armaceutical form of t!e active ingredient ciclosporin "ased on t!e microemulsion principle#!ic! reduces t!e varia"ilit$ of p!armaco%inetic parameters# and provides dose linearit$ of ciclosporin e&posure it! a more

consistent a"sorption profile and less influence from concomitant food inta%e. '!e formulation is a microemulsion

preconcentrate !ic! in p!armaco%inetic and clinical studies !as demonstrated t!at t!e correlation "eteen troug!

concentration and e&posure to ciclosporin is muc! stronger !en ciclosporin is given as Sandimmun Neoral t!an !en it is

given as Sandimmun. '!e formation of t!e microemulsion itself ta%es place in t!e presence of ater# eit!er in t!e form of a

"everage or in t!e form of t!e gastric fluid.

'!erapeutic indications

'ransplantation indications

Solid organ transplantation

( )revention of graft re*ection folloing %idne$# liver# !eart# com"ined !eart+lung# lung# or pancreas allogeneic transplantations.

( 'reatment of transplant re*ection in patients previousl$ receiving ot!er immunosuppressive agents.

,one marro transplantatiom

( )revention of graft re*ection folloing "one marro transplantation.( )revention or treatment of graft+versus+!ost disease -



Challenges in Immunosuppression

Cyclosporin complex pharmacokinetics impact clinical outcomes

1

Neoral ® Absorption Profiling demonstrates CsA absorption monitoring can result in more effective

immunosuppression2

ptimising immunosuppression re!uires individualisation of Neoral ® doses"

C#2 monitoring is validated as the most effective and practical single sampling point for Neoral ®

monitoring$

Cyclosporin blood level monitoring is standard practice for Neoral ® management of the transplant

recipient"

1. Lindholm A, Kahan BD. Clin Pharmacol Ther . 1993;55:!5"1#. 2. $ahalati K et al. Transplantation.1999;%#:55"%.

$. &ohn'ton A et al. Transplant Proc . !!!;3(')ppl 3A*:53+"5%+. ". Kahan BD. N Engl J Med . 19#9;31:15"13#.



Improving Patient utcomes in %ransplantation

%he importance of the absorption phase in Neoral ® pharmacokinetics1

A&C'#" monitoring in renal transplantation2

C#2 monitoring in liver transplantation$

Application of C#2 monitoring to all transplant recipients"

1. &ohn'ton A et al. Transplant Proc . !!!;3(')ppl 3A*:53+"5%+. . $ahalati K et al. Transplantation. 1999;%#:55"%. 3. Le-y

et al. Transplantation. !!!;%9:+3#. /. Belit'0y et al. Transplant Proc . !!!;3(')ppl 3A*:/5+"5+.



Neoral ® C#2 (onitoring)*hy the Need+

Issue

2 C#' ,trough- monitoring .as introduced to minimise toxicity1

2 C#' monitoring does not optimise the clinical benefits of Neoral ®2#"

2 A&C monitoring is cumbersome and expensive as a routine

management tool/

1. chida K et al. Dev Toxicol Environ Sci . 19#%;1/:1%3"1%%. . $ahalati 4 et al. Transplantation.

1999;%#:55"%. 3. &ohn'ton A et al. Transplant Proc . !!!;3(')ppl 3A* 53+"5%+. /. $ahalti K et al.

Transplantation. !!!;%9:+11/. 5. Amante A& et al. Clin Chem. 199%;/:19/"195.



0reatest egree of Intra#subect 3ariabilityccurs 1 to 2 4ours Post#ose

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/

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' '5$$ '566 1 15/ 2 25/ $ " 6 7 12

4ours Post#ose

&ohn'ton A et al. Transplant Proc . !!!;3(')ppl 3A*:53+"5%+.

8table Cardiac %ransplant 9ecipients: 1; 12; /2 *eeks Intrasubect 3ariability

in CsA (ean Concentration 3alues



Interpatient ?ariability of CsA Absorption 7otCaptured by C-:

Adapted from @ohnston A et al. Transplant Proc. :::B&/'-/0'.

&xtent and rate o absorption are highl. 0ariable3Patient di4erences are highlighted in the absorption phase3

ours Post-+ose

5

255

655

755

855

9555

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p o r i n C o n c e n t r a t i o n

1 n g / m L 2

C-5 C-2

A"C5-6

A"C5-6



C#' oes Not Predict Acute 9eection: Cmax oes

/"5/<

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>2/' 2/'#$'' $'1#"'' ?"''

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rant D et al. Transplantation. 1999;%:1133"113.



C#2 Is a 8urrogate (arker of Cmax

Cmax re!uires multiple blood samples and subse!uent

extrapolation of cyclosporin concentration#time curve

A single sampling point is the ideal monitoring tool

C#2 has the best correlation .ith Cmax in livertransplant patients

rant D et al. Transplantation. 1999;%:1133"113.



Choice of C#2 for Neoral ® (onitoring

Pharmacokinetic evidence for C#2

2 %he region of highest pharmacokinetic variability1

2 %he single sampling point that defines CsA absorption2

Pharmacodynamic evidence for C#2

2 Correlates .ith the period of maximum calcineurin inhibition$

2 (ore extensive and consistent I#2 suppression compared .ith C#'"

15 &ohn'ton A et al. Transplant Proc . !!!;3(')ppl 3A*:53+"5%+. 25 Belit'0y et al. Transplant Proc .

!!!;3(')ppl 3A*:/5+"5+. $5 alloran 6 et al. Transplantation. 1999;%#:135%"13%1. "5 +indhi 4 et al.

Transplantation. !!!;%9:/3"/3%.



2

C-2

Adapted from 4alloran P et al.Transplantation.9555B0D&9/0-909.

%ampling Pointours Post-+ose

5

25

65

75

85

955

C a l c i n e u r i n

I n h i b i t i o n 1 : 2

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m p

h o c . t e

s

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e 1 :

C-5 C-25

C-5

9 6

Calcineurin Inhibition !aximal and IL-2%uppression !ost Consistent at 2 ours

Post-+ose

'indhi # et al. Transplantation. :::B05&E-E0.



C#2: A 8ensitive Indicator of 9isk for 8ubclinical9eection

152 15'

(ean C#2 in Patients

*ith No 8c9

(ean C#2 in Patients

*ith 8c9

'57'

'57/

15''

15'/

151'

151/

152'

152/

P 7.!/

Barama A et al. Transplantation. !!!;%9:+5.

C # 2 A e v e l

, g @ m A -

D '5'"

D '5'$

(ean C#2 in Patients *ithout 8ubclinical 9eection ,No 8c9- or *ith 8ubclinical

9eection ,8c9- at Eiopsy 6 to 7 (onths Post#%ransplant



3idne$ 'ransplantC$closporinemia -ng/ml

CC00

=etermination at 9 hours after administration&

Month 1 250-350 ng/ml (preferably min 300 ng/ml)

Month 2 – Month 3 250-300 ng/ml

Month 4 – Month 12 250 ng/ml

After 1 year 200-250 ng/ml

CC22

=etermination at hours after administration&

Month 1 1600-1800 ng/ml

Month 2 1400-1600 ng/ml

Month 3 1200-1400 ng/ml

After 1 year 00-800 ng/ml



• =ay 9 - =ay 3• =ay D – =ay :

• =ay 9 – =ay 0:

• =ay 09 – =ay 5:• After 5: =ays

• SIROLIMUS& 0 – 3 ng$ml

• 9/ - : ng$ml• 9: – : ng$ml

• / – 9: ng$ml

• / - 9: ng$ml• / ng$ml

(ACR$L&!IA1ng/ml

Ad0erse reactions in



• 8hen immunosuppressant drugs wea+en the immune system, the body becomesless resistant to infection. Any infections that develop will be more di6cult totreat because of this. These drugs also increase the li+elihood of uncontrolledbleeding due to in*ury or infection.

• People ta+ing immunosuppressant drugs should be careful to avoid catching aninfection. Precautions include&

• freuent hand washing

• avoiding sports in which in*uries occur

• e2tra care when using sharp ob*ects such as +nives or raors

• avoiding close contact with people who have infections or colds

A ph.sician should be notifed immediatel. hen the olloing s.mptomsoccur:

• fever or chills

• pain in the lower bac+, on the sides

• pain or di6culty urinating

• unusual bruising or bleeding

• blood in your urine

• stools that are bloody or blac+

Ad0erse reactions inimmunosuppressant drugs



Immunosuppressant drugs can cause adverse reactions and birth defects.

Ph.sicians should be made aare o the olloing conditions beoreimmunosuppressant drugs are prescribed:

• allergies

• pregnancy

• lactation• shingles or chic+enpo2

• +idney or liver disease

• intestinal problems

• The most signicant side e)ect of immunosuppressant drugs is an increased ris+ ofinfection. The drugs can also put you at a higher ris+ for cancer because the immunesystem also protects you from this disease.

• "ther, less serious side e)ects can include loss of appetite, nausea, vomiting,increased hair growth, and hand trembling. These e)ects typically subside as thebody ad*usts to the immunosuppressant drugs.

(he olloing side e4ects indicate the need or immediate attention:

• a feeling of being unusually tired or wea+

• fever or chills

• freuent urination• Immunosuppressant drugs can interact with many other medications. This can cause

dangerous e)ects in which the immunosuppressants may lose or even increase theire)ect. The primary caregiver should be made aware of any prescription or over-the-counter medications their patients are ta+ing while on immunosuppressant therapy.

l i



• Transplantation immunology is comple2.

• "ur Immunogenetic Centre provide e2pandedimmunological monitoring together with virologicaland drug monitoring of the transplanted patients.

• "ur goal is to o)er complete integrated monitoringdata and to full (<I 'tandards.

• 8e are open for collaborative wor+ and research

pro*ects within (<I.

• Clinical and laboratory scientists should wor+together as a team in order to have a complete

overview of the transplanted patients.

Conclusions



Posttransplantmanagement in solidorgan transplantation

1%$(

Pro3 IleanaConstantinescu

?hat means post transplant management o



?hat means post transplant management othe patient

• Management of s+in cancer in solid organ transplant recipients

• #enal function and nonrenal solid organ transplantation

• Treatment and prevention of post-transplant lymphoproliferative disorders

• >ong-term management of adult liver transplant recipients

• Clinical manifestations, diagnosis, and treatment of cytomegalovirus infection in lung transplant recipients

• Prevention of cytomegalovirus infection in lung transplant recipients

• =evelopment of malignancy following solid organ transplantation

• Infection in the solid organ transplant recipient

• "steoporosis after solid organ or stem cell transplantation

• 'ystemic treatment of advanced cutaneous suamous and basal cell carcinomas

• "verview of care of the adult +idney transplant recipient

• 'olid organ transplantation in 4I?-infected individuals

• !anagement o the hematopoietic cell transplant recipient in the immediate posttransplant period

• Treatment and prognosis of cutaneous suamous cell carcinoma

• &%$( - http://3esot3org

!anagement o s@in cancer in solid organ tran

http://www.uptodate.com/contents/management-of-skin-cancer-in-solid-organ-transplant-recipients?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=1%7E150

http://www.uptodate.com/contents/renal-function-and-nonrenal-solid-organ-transplantation?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=2%7E150

http://www.uptodate.com/contents/treatment-and-prevention-of-post-transplant-lymphoproliferative-disorders?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=3%7E150


http://www.uptodate.com/contents/long-term-management-of-adult-liver-transplant-recipients?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=4%7E150

http://www.uptodate.com/contents/clinical-manifestations-diagnosis-and-treatment-of-cytomegalovirus-infection-in-lung-transplant-recipients?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=6%7E150


http://www.uptodate.com/contents/prevention-of-cytomegalovirus-infection-in-lung-transplant-recipients?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=7%7E150

http://www.uptodate.com/contents/development-of-malignancy-following-solid-organ-transplantation?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=9%7E150

http://www.uptodate.com/contents/infection-in-the-solid-organ-transplant-recipient?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=11%7E150

http://www.uptodate.com/contents/osteoporosis-after-solid-organ-or-stem-cell-transplantation?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=13%7E150

http://www.uptodate.com/contents/systemic-treatment-of-advanced-cutaneous-squamous-and-basal-cell-carcinomas?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=15%7E150


http://www.uptodate.com/contents/overview-of-care-of-the-adult-kidney-transplant-recipient?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=19%7E150

http://www.uptodate.com/contents/solid-organ-transplantation-in-hiv-infected-individuals?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=28%7E150

http://www.uptodate.com/contents/management-of-the-hematopoietic-cell-transplant-recipient-in-the-immediate-posttransplant-period?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=32%7E150


http://www.uptodate.com/contents/treatment-and-prognosis-of-cutaneous-squamous-cell-carcinoma?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=42%7E150

http://www.uptodate.com/contents/treatment-and-prognosis-of-cutaneous-squamous-cell-carcinoma?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=42%7E150



http://www.uptodate.com/contents/solid-organ-transplantation-in-hiv-infected-individuals?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=28%7E150

http://www.uptodate.com/contents/overview-of-care-of-the-adult-kidney-transplant-recipient?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=19%7E150



http://www.uptodate.com/contents/osteoporosis-after-solid-organ-or-stem-cell-transplantation?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=13%7E150

http://www.uptodate.com/contents/infection-in-the-solid-organ-transplant-recipient?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=11%7E150

http://www.uptodate.com/contents/development-of-malignancy-following-solid-organ-transplantation?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=9%7E150

http://www.uptodate.com/contents/prevention-of-cytomegalovirus-infection-in-lung-transplant-recipients?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=7%7E150



http://www.uptodate.com/contents/long-term-management-of-adult-liver-transplant-recipients?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=4%7E150



http://www.uptodate.com/contents/renal-function-and-nonrenal-solid-organ-transplantation?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=2%7E150

http://www.uptodate.com/contents/management-of-skin-cancer-in-solid-organ-transplant-recipients?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=1%7E150

http://www.uptodate.com/contents/management-of-skin-cancer-in-solid-organ-transplant-recipients?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=1~150




!anagement o s@in cancer in solid organ transplant recipientsI#(R$+"C(I$#

• 'olid organ transplant recipients are at increased ris+ for cutaneous malignancies, anding related to the long-term use of immunosuppression. Gecause some s+in cancersdemonstrate aggressive biologic behavior in the setting of immunosuppression, care

must be ta+en to identify and treat early lesions appropriately. In addition to treatmentsthat directly target cutaneous malignancies, modulation of immunosuppression andpreventive measures often play an important role in the management of these patients."rgan transplant recipients with a history of s+in cancer should be followed closely forthe development of new lesions, locally recurrent lesions, and metastatic disease.

• The management of s+in cancers in organ transplant recipients will be reviewed here. The epidemiology and ris+ factors for s+in cancers in organ transplant recipients, as wellas a summary of other malignancies that develop with increased freuency after solidorgan transplantation, are discussed separately.

%"A!$"% C&LL CARCI#$!A

• 'uamous cell is carcinoma !'CC% is the most common cutaneous malignancy in solidorgan transplant recipients . As in the immunocompetent population, cutaneous 'CC ismost li+ely to occur in patients with fair s+in.

• In comparison to 'CC in immunocompetent patients, 'CC in organ transplant recipientsis more li+ely to manifest as aggressive disease . The prognosis is poor for the / to D

percent of patients who develop metastasesB in a retrospective study that included /Dorgan transplant recipients with distant or systemic metastases of cutaneous 'CC, thethree-year disease-specic survival rate was 5 percent . Thus, once detected, prompt,appropriate management of early 'CC is essential.

Patient e0aluation H All lesions that are suspicious for 'CC should be pathologicallye2amined to conrm the diagnosis and to evaluate for features associated withaggressive disease. Giopsies of papular or nodular lesions should e2tend at least into the

deep reticular dermis.

Renal unction and nonrenal solid organ trans





http://www.uptodate.com/contents/renal-function-and-nonrenal-solid-organ-transplantation?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=2~150




Renal unction and nonrenal solid organ transplantationI#(R$+"C(I$#

• As outcomes following nonrenal solid organ transplantation have improved, chronic +idney

disease !C=% has become an increasingly prevalent complication in this population . C=occurs despite advancements in immunosuppression and perioperative management, as wellas attention to cardiovascular ris+ factors and infectious complications .

• The development of C= is associated with enhanced morbidity and mortality .

PR&$P&RA(IB& &BAL"A(I$# $ 'I+#&D "#C(I$#

• As a general rule, the preoperative evaluation of +idney function in nonrenal solid organtransplantation candidates should focus upon establishing the li+elihood of being left withadeuate +idney function posttransplant and the chance of progression to end-stage renaldisease !('#=%. Patients who are li+ely to have stage E or stage / chronic +idney disease!C=% after the early posttransplant period and$or those with established primary renal diseasethat is li+ely to progress at a rapid pace !thereby reuiring chronic +idney replacement therapy

shortly after transplant% should be listed for combined organ transplant. It should be notedthat, in an era of ever-increasing organ shortage, in which waiting times for +idneys arelengthening, combined nonrenal and renal organ transplantation should be considered very *udiciously.

• The vast ma*ority of patients with normal or mild impairment in +idney function should receivea nonrenal solid organ transplant alone. 4owever, normal or near-normal serum creatininelevels do not necessarily reJect normal +idney function, especially in states of heart failure orliver disease, where a)ected patients freuently have poor nutritional status, low muscle

mass, weight loss, and edema.

(reatment and pre0ention o post-transplant l.mph





http://www.uptodate.com/contents/treatment-and-prevention-of-post-transplant-lymphoproliferative-disorders?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=3~150




(reatment and pre0ention o post transplant l.mphprolierati0e disorders

1P(L+I#(R$+"C(I$#

• Post-transplant lymphoproliferative disorders 1P(L+ are lymphoid and$or plasmacyticproliferations that occur in the setting of solid organ or allogeneic hematopoietic cell

transplantation as a result of immunosuppression. They are among the most seriousand potentially fatal complications of transplantation. 8hile the ma*ority appears to berelated to the presence of (pstein-Garr virus !(G?%, (G?-negative disease does occur.

Three general types of PT>= have been described in transplant recipients&

• K&arl. lesion !plasmacytic hyperplasia and infectious mononucleosis-li+e PT>=% – Thispresents as an infectious mononucleosis-type acute illness characteried by polyclonal

G cell proliferation with no evidence to suggest malignant transformation.• KPol.morphic P(L+ – Polymorphic PT>= are polyclonal or monoclonal lymphoid

inltrates that demonstrate evidence of malignant transformation but do not meet allof the criteria for one of the G cell or T$7 cell lymphomas recognied inimmunocompetent patients.

• K!onomorphic P(L+ – Monomorphic PT>= are monoclonal lymphoid proliferationsthat meet the criteria for one of the G cell or T$7 cell lymphomas recognied in

immunocompetent patients.• These conditions lie along a continuum of disease and are categoried by the ::D

84" classication system as PT>= 3 $ importance* small > cell l.mphoidneoplasms 1eg* ollicular l.mphomas* small l.mphoc.tic l.mphoma andmarginal ,one 1!AL( l.mphomas arising in the post-transplant settingare not considered P(L+3







Clinical maniestations* diagnosis* and treatment o c.tomegalo0irus inection in lung transplant recipientsI#(R$+"C(I$#

• Cytomegalovirus !CM?%, a member of the betaherpesvirus group, remains an important cause of

morbidity and mortality in lung transplant recipients. It is the second most common infection among lungtransplant recipients, after bacterial pneumonia.

• 8hile the development and availability of potent antiviral agents has decreased CM?-related mortality,there is a growing body of evidence that the indirect e)ects of CM? may be eually important or evenmore important than its direct e)ects of tissue in*ury and infection . CM?-induced immunosuppressionmay lead to infection with other opportunistic organisms. In addition, CM? infection and disease havebeen associated with acute and chronic re*ection !bronchiolitis obliterans syndrome% in some, but not allstudies.

• The approach to the diagnosis and treatment of CM? infections in lung transplant recipients continues to

evolve as transplant specialists gain e2perience using molecular diagnostic techniues and the potentoral antiviral agent, valganciclovir. The epidemiology, clinical features, diagnosis, and treatment of CM?infection in lung transplant recipients will be discussed here. Prevention of CM? infection in lungtransplant recipients, as well as infectious complications due to pathogens other than CM?, are discussedelsewhere.

&PI+&!I$L$FD

• Primary cytomegalovirus !CM?% infection is acuired through close physical contact involving directinoculation with infected cells or body Juids. <ollowing primary infection, CM? infection persists for life.

Population studies document a gradual increase in CM? seropositivity through young adulthood.Although there is considerable variability, more than one-half of adults in the Lnited 'tates haveserologic evidence of previous infection.

• CM? infection following transplantation can be acuired in one of several ways

Pre0ention o c.tomegalo0irus inection in lun

http://www.uptodate.com/contents/clinical-manifestations-diagnosis-and-treatment-of-cytomegalovirus-infection-in-lung-transplant-recipients?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=6~150







http://www.uptodate.com/contents/prevention-of-cytomegalovirus-infection-in-lung-transplant-recipients?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=7~150




Pre0ention o c.tomegalo0irus inection in lung transplant recipientsI#(R$+"C(I$#

• Cytomegalovirus !CM?%, a member of the betaherpesvirus group, remains an importantcause of infection, resulting in substantial morbidity and increased mortality in lung

transplant recipients. It is the second most common infection among lung transplantrecipients after bacterial pneumonia.

• 8hile the development and availability of potent antiviral agents has decreased CM?-related mortality, there is a growing body of evidence that the indirect e)ects of CM?may be eually important or even more important than its direct e)ects of tissue in*uryand infection . CM?-induced immunosuppression may lead to infection with otheropportunistic organisms. In addition, CM? infection and disease have been associated

with acute and chronic re*ection !bronchiolitis obliterans syndrome% in some but not allstudies.

• The approach to prevention of CM? infections in lung transplant recipients continues toevolve as transplant specialists gain e2perience using molecular diagnostic techniuesand the potent oral antiviral agent valganciclovir. The prevention of CM? infection inlung transplant recipients will be discussed here. The clinical manifestations, diagnosis,and treatment of CM? infection in lung transplant recipients and infectious

complications due to agents other than CM? are discussed elsewhere.&PI+&!I$L$FD

• Primary CM? infection is acuired through close physical contact involving directinoculation with infected cells or body Juids. <ollowing primary infection, CM? infectionpersists for life. Population studies document a gradual increase in CM? seropositivitythrough young adulthood. Although there is considerable variability, more than one-halfof adults in the Lnited 'tates have serologic evidence of previous infection.

• CM? infection following transplantation can be acuired in one of several ways

+e0elopment o malignanc. olloing solid organ t





http://www.uptodate.com/contents/development-of-malignancy-following-solid-organ-transplantation?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=9~150




+e0elopment o malignanc. olloing solid organ transplantation

I#(R$+"C(I$# A#+ $B&RBI&?

• The chronic use of immunosuppressive agents to prevent allograft re*ection increases

the long-term ris+ of malignancy, compared with that of the general population. Thistopic will review the general issue of malignancy following solid organ transplantation. The problems of second malignancies following bone marrow transplantation and thedevelopment of lymphoproliferative disorders following solid organ transplantation arediscussed separately.

F&#&RAL &PI+&!I$L$FD

• There is an increased ris+ of a wide range of cancers associated with solid organtransplantation. The most e2tensive data come from a cohort study that analyed thefreuency of malignancy in over 93/,::: solid organ transplant recipients during theperiod 95D3 to ::D . The most common organs transplanted included +idney, liver,heart, and lung !in /D, , 9:, and E percent of cases, respectively%.

• "verall, malignancy was identied in over 9:,0/0 cases, which correlated with astandardied incidence ratio !'I#% of .9: !5/ CI .:0-.9E%, compared with the generalpopulation, and an e2cess absolute ris+ !(A#% of 395 cases per 9::,::: person-years.

• A signicantly increased ris+ of malignancy was associated with more than : di)erentprimary sites. The tumor sites with a vefold or greater increase, compared with thegeneral population, included the following&

• aposi sarcoma !'B 'I# 09 and (A# 9/%

Inection in the solid organ transplant recipien





http://www.uptodate.com/contents/infection-in-the-solid-organ-transplant-recipient?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=11~150




Inection in the solid organ transplant recipientI#(R$+"C(I$#

• 'olid organ transplantation has increased worldwide since the rst successful human +idneytransplant was performed in 95/E. As immunosuppressive agents and graft survival haveimproved, infection and malignancy have become the main barriers to disease-free survival

after organ transplantation. As a result of the growing population of immunosuppressed patientswith prolonged survival, an increased incidence and spectrum of opportunistic infections isobserved . Nuidelines for the diagnosis and treatment of infection in transplant recipients havebeen developed .

• The ris+s of infection and an overview of specic infections in the solid organ transplantrecipient will be reviewed here. The pretransplant evaluation for solid organ and hematopoieticcell transplant !4CT% recipients, prophyla2is of infections in solid organ transplant and 4CTrecipients, and an overview of infections following 4CT are discussed separately.

F&#&RAL PRI#CIPL&%

• ?hen inection occurs* earl. and specifc diagnosis and rapid and aggressi0etreatment are essential to good clinical outcomes3

• KPotential etiologies of infection in these patients are diverse, including common, community-acuired bacterial and viral diseases and uncommon opportunistic infections of clinicalsignicance only in immunocompromised hosts . Pulmonary processes can progress rapidly and

may constitute medical emergencies . These include infections due to $neumocystis %iro&ecii 1ormerl. $. carinii * 'ocardia asteroides* Aspergillusspp* Cryptococcusneoormans* c.tomegalo0irus 1C!B* 0aricella-,oster 0irus 1BGB* inHuen,a*respirator. s.nc.tial 0irus 1R%B* hodococcus eui * and *egionella spp3

• KInJammatory responses associated with microbial invasion are impaired byimmunosuppressive therapy, which results in diminished symptoms and muted clinical andradiologic ndings. As a result, infections are often advanced !disseminated% at the time ofclinical presentation.

$steoporosis ater solid organ or stem cell tr





http://www.uptodate.com/contents/osteoporosis-after-solid-organ-or-stem-cell-transplantation?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=13~150




$steoporosis ater solid organ or stem cell transplantationI#(R$+"C(I$#

• Transplantation has become an established therapy for end-stage +idney, heart, lung,and liver diseases, as well as for several hematologic disorders. Improved survival of

transplant recipients has raised awareness of post-transplant complications, such asosteoporosis. Post-transplant osteoporosis and fracture occur in a substantialproportion of patients.

• The pathogenesis, clinical manifestations, and management of bone loss after solidorgan !with the e2ception of renal transplant% or stem cell transplantation will bereviewed here. Management of bone loss after renal transplantation is discussedelsewhere.

PA($F&#&%I%

• Transplant-related osteoporosis and fracture are due to both pretransplant and post-transplant factors

Pretransplant bone status H Many patients undergoing transplantation already havelo bone mineral densit. 1>!+3

(he mechanism appears to 0ar. ith the underl.ing disease:

• KIn patients with severe heart failure !7ew Oor+ 4eart Association 7O4AQ classes IIIand I?% who are candidates for cardiac transplantation, chronic +idney disease,0itamin + defcienc.* secondar. h.perparath.roidism* h.pogonadism*

chronic use o heparin and/or loop diuretics* and reduced ph.sical acti0it.ma. contribute to lo >!+3

% t i t t t d d t





http://www.uptodate.com/contents/systemic-treatment-of-advanced-cutaneous-squamous-and-basal-cell-carcinomas?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=15~150




%.stemic treatment o ad0anced cutaneous suamous and basal cell carcinomas

I#(R$+"C(I$#

• Gasal cell carcinoma and suamous cell carcinoma of the s+in, together referred to

as nonmelanoma s+in cancer !7M'C%, are the most commonly diagnosed malignantneoplasms in the Caucasian population of the Lnited 'tates. Gecause manypatients are treated as outpatients in an o6ce setting, reliable statistics are di6cultto obtain. 7onetheless, the 7ational Cancer Institute estimates that appro2imatelytwo million new cases occurred in :9 .

• The vast ma*ority of patients can be successfully managed with a variety of simpleprocedures, such as cryotherapy, curettage and electrodesiccation, topical

treatments !/-Juorouracil, imiuimod%, or simple surgical e2cision. 8hen lesions aremore advanced, Mohs micrographic surgery, more e2tensive surgical resection, orradiation therapy generally are generally su6cient to control locoregional disease.

• =espite their high prevalence, these nonmelanoma s+in cancers are rarely fatal. Itis estimated that in :9, appro2imately 9::: patients died of the disease.'uamous cell carcinomas are biologically more aggressive, and neglected lesionscan be life threatening due to local e2tension or metastasis. In contrast, basal cell

carcinoma is only very rarely life threatening.• The use of systemic therapy is limited to patients with distant metastases or locally

advanced disease that cannot be adeuately managed with surgical orradiotherapeutic techniues.

• 'ystemic chemotherapy for basal cell and suamous cancers of the s+in could be asolution. The treatment of localied basal cell and suamous cell carcinomas is anissue to be discussed.

$0er0ie o care o the adult @idne. transplan





http://www.uptodate.com/contents/overview-of-care-of-the-adult-kidney-transplant-recipient?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=19~150




$ e e o ca e o e adu d e. a sp at recipient

I#(R$+"C(I$#

• idney transplantation is the treatment of choice for end-stage renal disease . Asuccessful +idney transplant improves the uality of life and reduces the mortality

ris+ for most patients when compared with maintenance dialysis. 4owever,patients reuire close follow-up after transplantation since they are on comple2immunosuppressive regimens that render them susceptible to infection,malignancy, and cardio0ascular disease 1CB+3 In addition, patients often havemultiple comorbidities due to, or as a cause of, their underlying end-stage renaldisease.

• 8hereas patients are generally followed by a transplant specialist for the rstthree to si2 months following transplant, thereafter they may be seen primarily bya general nephrologist or internist, who is often able to address e2istingcomorbidities. 8hether a patient is followed by a transplant nephrologist, generalnephrologist, or internist often depends upon the availability of services inpro2imity to the patient. 8hile many believe that transplant nephrologists shouldbe directly involved in care of transplant recipients for the life of the graft, this isoften not practical. Communication between the internist or community-basednephrologist and the transplant center is important for optimal care of the patient,however.

• This topic reviews the general medical care of the +idney transplant recipientincluding recommendations for monitoring allograft function and minimi,ing the

ris@ o inections* malignancies* bone disease* CB+, and diabetes. These arecommon medical problems encountered after transplantation are also discussed.

%olid organ transplantation in IB-inected ind





http://www.uptodate.com/contents/solid-organ-transplantation-in-hiv-infected-individuals?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=28~150




g pi0iduals

I#(R$+"C(I$#

• >iver, +idney, and heart transplantation are the current treatments of choice foradvanced organ failure. 4owever, human immunodeciency virus !4I?% infection was

traditionally considered an absolute contraindication for transplantation . "ne of theprincipal concerns was that immunosuppression would accelerate 4I?$acuired immunedeciency syndrome !AI='%, resulting in increased mortality and a ;waste; of organs.

• 'ince highly active antiretroviral therapy !4AA#T% became widely available in 9550, theprognosis of 4I? infection has dramatically improved. There have been signicantdecreases in morbidity and mortality, and, for many individuals with well-controlled viralreplication, 4I?$AI=' is now a chronic, manageable disease.

• Previously, 4I?-infected individuals with very advanced disease freuently died fromopportunistic infections !"Is%. Among such individuals, the presence of chronic diseases,such as renal insu6ciency, coronary artery disease, diabetes mellitus, or liver failure!associated with hepatitis G 4G?Q or C virus 4C?Q coinfection%, were not signicantcauses of mortality. The situation is currently uite di)erent as these comorbidities, aswell as others, are real medical problems for many individuals with well-controlled 4I?replication.

• 'uch improvements in the long-term prognosis of those with 4I? infection have

prompted many transplant programs to reevaluate their policies regarding the e2clusionof patients with 4I? infection. A review of the issues surrounding solid organtransplantation in 4I?-infected patients is presented here.

$"(C$!&% >&$R& IFLD AC(IB& A#(IR&(R$BIRAL (&RAPD 1AAR(

• Prior to the availability of a reliable diagnostic test for 4I? infection, some individualsun+nowingly infected with 4I? underwent solid organ transplantation . "thers acuired

4I? infection by receiving an organ from a 4I?-positive individual.

!anagement o the hematopoietic cell transpla





http://www.uptodate.com/contents/management-of-the-hematopoietic-cell-transplant-recipient-in-the-immediate-posttransplant-period?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=32~150




!anagement o the hematopoietic cell transplant recipient in the immediate posttransplant periodI#(R$+"C(I$#

• Among patients undergoing hematopoietic cell transplantation !4CT%, advances inhematopoietic supportB improvements in antibiotics, antifungal agents, and antiviral drugsBand better medications to control side e)ects of treatment such as nausea, vomiting, diarrheaand pain have all had a ma*or impact on the clinical course.

• In terms of decreased morbidity and mortality after autologous transplantation, probably thesingle most important advance has been the introduction of mobilied peripheral bloodprogenitor cells !PGPCs% as the source of hematopoietic stem cells. This approach results inmore rapid recovery, which has signicantly reduced the duration of antibiotic therapy, thedegree of mucositis, the length of hospitaliation, and the ris+ of the transplant procedureitself. These positive developments have resulted in a mar+ed decline in the discomfort thatpatients e2perience in the transplant setting.

• The term ;hematopoietic cell transplantation; !4CT% will be used throughout this review as ageneral term to cover transplantation of progenitor cells from any source !eg, bone marrow,peripheral blood, umbilical cord blood%. "therwise, the source of such cells will be specied!eg, autologous PGPC transplantation%.

• Neneral supportive care measures for patients following 4CT and long term complications of4CT will be reviewed here . 4ematopoietic support after 4CT and the prevention andtreatment of acute and chronic graft versus host disease are discussed separately.

• The diagnosis and treatment of pulmonary, renal, and infectious complications following 4CTare also presented separately.

(reatment and prognosis o cutaneous suamous ce








http://www.uptodate.com/contents/treatment-and-prognosis-of-cutaneous-squamous-cell-carcinoma?source=search_result&search=post+solid+organ+transplantation+management&selectedTitle=42~150




p g ll carcinoma

I#(R$+"C(I$#

• Cutaneous suamous cell carcinoma !'CC% is a common cancer arising from malignantproliferation of the +eratinocytes of the epidermis. Treatment of cutaneous 'CC is indicatedsince progression of the tumor may lead to local tissue destruction or metastasis resulting in

signicant morbidity or death. (arly treatment provides the best opportunity to cure cutaneous'CC.

• In contrast to basal cell carcinoma !GCC%, which rarely metastasies, around to / percent ofcutaneous 'CCs metastasie to regional lymph nodes or more distant sites. The approach totreatment is dependent upon the presence or absence of tumor features and patientcharacteristics that portend an increased ris+ for aggressive tumor behavior. Cutaneous 'CCsthat do not have high-ris+ features have low freuencies of recurrence and metastasis.

• The treatment of cutaneous 'CCs ithout features associated with aggressive behavior !low-ris+ cutaneous 'CC% and the prognosis of cutaneous 'CC will be reviewed here. Themanagement of high-ris+ and metastatic cutaneous 'CCs, the treatment of +eratoacanthomas,and the ris+ factors, clinical features, and diagnosis of cutaneous 'CC are reviewed separately.

APPR$AC ($ (R&A(!&#(

• The ris+ of locoregional recurrence and regional or distant metastasis is the most importantfactor for determining the approach to the treatment for cutaneous suamous cell carcinoma!'CC%. (2amples of characteristics that impact the ris+ for recurrence and metastasis include

the site, sie, and histologic features of a tumor, as well as patient comorbidities . ;4igh-ris+;'CCs are tumors that e2hibit characteristics that are associated with an elevated ris+ foraggressive tumor behavior.

• A consensus on the specic characteristics that dene high-ris+ 'CC has not been establishedand ma*or entities such as the 7ational Comprehensive Cancer 7etwor+ !7CC7% and theAmerican @oint Committee on Cancer !A@CC% have described dissimilar ;high-ris+; criteria . 8efollow the 7CC7 criteria when categoriing tumors as high-ris+ or low-ris+ for determining the

approach to treatment . The features of high-ris+ cutaneous 'CC are reviewed in greater detailseparately.







$rgan donation(ransplant coordination

Pro3 Ileana

Constantinescu



Autograt



Autograt• Autograts are the transplant o tissue to the same person. 'ometimes this is done with

surplus tissue, tissue that can regenerate, or tissues more desperately needed elsewhere!e2amples include s+in grafts, vein e2traction for CAGN, etc.%. 'ometimes an autograft is done toremove the tissue and then treat it or the person before returning it !e2amples includestem cell autograft and storing blood in ad0ance o surger.%. In a rotationplasty, a distal *oint

is used to replace a more pro2imal oneB typically a foot or an+le *oint is used to replace a +nee *oint. The person1s foot is severed and reversed, the +nee removed, and the tibia *oined with thefemur.

Allograt and allotransplantation

• An allograt is a transplant o an organ or tissue beteen to geneticall. non-identicalmembers o the same species. Most human tissue and organ transplants are allograts3 =ueto the genetic di)erence between the organ and the recipient, the recipient1s immune s.stem will identify the organ as foreign and attempt to destroy it, causing transplant re*ection. The ris+

of transplant re*ection can be estimated by measuring the Panel reactive antibody 1PRA level.Isograt

• A subset o allograts in hich organs or tissues are transplanted rom a donor to ageneticall. identical recipient 1such as an identical tin3 Isografts are di)erentiated fromother types of transplants because while the. are anatomicall. identical to allograts* the.do not trigger an immune response3

Jenograt and xenotransplantation

• A transplant o organs or tissue rom one species to another. An e2ample is porcine heartvalve transplant, which is uite common and successful. Another e2ample is attempted piscine-primate !sh to non-human primate% transplant of islet !i.e. pancreatic or insular tissue% tissue. Thelatter research study was intended to pave the way for potential human use if successful.4owever, 2enotransplantion is often an e2tremely dangerous type of transplant because of theincreased ris+ of non-compatibility, re*ection, and disease carried in the tissue.

%plit transplants

http://en.wikipedia.org/w/index.php?title=Vein_extraction&action=edit&redlink=1

http://en.wikipedia.org/wiki/CABG

http://en.wikipedia.org/wiki/Hematopoietic_stem_cell_transplantation

http://en.wikipedia.org/wiki/Rotationplasty

http://en.wikipedia.org/wiki/Interphalangeal_articulations_of_foot

http://en.wikipedia.org/wiki/Tibia

http://en.wikipedia.org/wiki/Femur

http://en.wikipedia.org/wiki/Species

http://en.wikipedia.org/wiki/Immune_system

http://en.wikipedia.org/wiki/Panel_reactive_antibody

http://en.wikipedia.org/wiki/Immunology

http://en.wikipedia.org/wiki/Fish

http://en.wikipedia.org/wiki/Primate



http://en.wikipedia.org/wiki/Primate


http://en.wikipedia.org/wiki/Immunology

http://en.wikipedia.org/wiki/Panel_reactive_antibody

http://en.wikipedia.org/wiki/Immune_system

http://en.wikipedia.org/wiki/Species

http://en.wikipedia.org/wiki/Femur

http://en.wikipedia.org/wiki/Tibia

http://en.wikipedia.org/wiki/Interphalangeal_articulations_of_foot

http://en.wikipedia.org/wiki/Rotationplasty

http://en.wikipedia.org/wiki/Hematopoietic_stem_cell_transplantation

http://en.wikipedia.org/wiki/CABG

http://en.wikipedia.org/w/index.php?title=Vein_extraction&action=edit&redlink=1



%plit transplants• 'ometimes a deceased-donor organ, usually a liver, may be divided between two recipients,

especially an adult and a child. This is not usually a preferred option because the transplantation of awhole organ is more successful.

• +omino transplants

• In people with cystic brosis, where both lungs need to be replaced, it is a technically easieroperation with a higher rate of success to replace both the heart and lungs of the recipient withthose of the donor. As the recipient1s original heart is usually healthy, it can then be transplantedinto a second recipient in need of a heart transplant. Another e2ample of this situation occurs with aspecial form of liver transplant in which the recipient su)ers fromfamilial amyloidotic polyneuropathy , a disease where the liver slowly produces a protein thatdamages other organs. The recipient1s liver can then be transplanted into an older person for whomthe e)ects of the disease will not necessarily contribute signicantly to mortality.

• This term also refers to a series of living donor transplants in which one donor donates to the highestrecipient on the waiting list and the transplant center utilies that donation to facilitate multipletransplants. These other transplants are otherwise impossible due to blood type or antibody barriersto transplantation. The ;Nood 'amaritan; +idney is transplanted into one of the other recipients,whose donor in turn donates his or her +idney to an unrelated recipient. =epending on the person onthe waiting list, this has sometimes been repeated for up to si2 pairs, with the nal donor donatingto the person at the top of the list. This method allows all organ recipients to get a transplant even iftheir living donor is not a match to them. This further benets people below any of these recipientson waiting lists, as they move closer to the top of the list for a deceased-donor organ.

@ohns 4op+ins Medical Center in Galtimore and 7orthwestern Lniversity 1s7orthwestern Memorial 4ospital have received signicant attention for pioneering transplants of this+ind.

• In <ebruary :9, the last lin+ in a record 0:-person domino chain of : +idney transplants wascompleted.

A>$ i tibl t l t

http://en.wikipedia.org/wiki/Cystic_fibrosis

http://en.wikipedia.org/wiki/Transthyretin-related_hereditary_amyloidosis

http://en.wikipedia.org/wiki/Protein

http://en.wikipedia.org/wiki/Blood_type

http://en.wikipedia.org/wiki/Good_Samaritan

http://en.wikipedia.org/wiki/Johns_Hopkins_Medical_Center

http://en.wikipedia.org/wiki/Northwestern_University

http://en.wikipedia.org/wiki/Northwestern_Memorial_Hospital

http://en.wikipedia.org/wiki/Northwestern_Memorial_Hospital

http://en.wikipedia.org/wiki/Northwestern_University

http://en.wikipedia.org/wiki/Johns_Hopkins_Medical_Center

http://en.wikipedia.org/wiki/Good_Samaritan

http://en.wikipedia.org/wiki/Blood_type

http://en.wikipedia.org/wiki/Protein

http://en.wikipedia.org/wiki/Transthyretin-related_hereditary_amyloidosis

http://en.wikipedia.org/wiki/Cystic_fibrosis



A>$-incompatible transplants• Gecause very young children !generally under 9 months, but often as old as E months% do

not have a well-developed immune system, it is possible for them to receive organs fromotherwise incompatible donors. This is +nown as AG"-incompatible !AG"i% transplantation.Nraft survival and peoples mortality is appro2imately the same between AG"i and AG"-compatible !AG"c% recipients. 8hile focus has been on infant heart transplants, the principles

generally apply to other forms of solid organ transplantation.

• The most important factors are that the recipient not have produced isohemagglutinins, andthat they have low levels of T cell-independent antigens. Lnited 7etwor+ for "rgan 'haring !L7"'%regulations allow for AG"i transplantation in children under two years of age ifisohemagglutinin titers are 9&E or below, and if there is no matching AG"c recipient. 'tudieshave shown that the period under which a recipient may undergo AG"i transplantation maybe prolonged by e2posure to nonself A and G antigens. <urthermore, should the recipient !for

e2ample, type G-positive with a type AG-positive graft% reuire eventual retransplantation, therecipient may receive a new organ of either blood type.

• >imited success has been achieved in AG"-incompatible heart transplants in adults, thoughthis reuires that the adult recipients have low levels of anti-A or anti-G antibodies. idneytransplantation is more successful, with similar long-term graft survival rates to AG"ctransplants.

(ransplantation in obese indi0iduals• Lntil recently, people labeled as obese were not considered appropriate candidates for renal

transplantation. In ::5, the physicians at the Lniversity of Illinois Medical Center performedthe rst robotic +idney transplantation in an obese recipient and have continued to transplantpeople with Gody Mass Inde2 !GMI%Ss over / using robotic surgery. As of @anuary :9E, over9:: people that would otherwise be turned down because of their weight have successfullybeen transplanted.

http://en.wikipedia.org/wiki/Isohemagglutinin

http://en.wikipedia.org/wiki/Antigen

http://en.wikipedia.org/wiki/United_Network_for_Organ_Sharing


http://en.wikipedia.org/wiki/Obese

http://en.wikipedia.org/wiki/University_of_Illinois_Medical_Center

http://en.wikipedia.org/wiki/Body_Mass_Index

http://en.wikipedia.org/wiki/Robotic_surgery

http://en.wikipedia.org/wiki/Robotic_surgery

http://en.wikipedia.org/wiki/Body_Mass_Index


http://en.wikipedia.org/wiki/Obese



http://en.wikipedia.org/wiki/Antigen


http://en.wikipedia.org/wiki/Organ_transplantation



anted

• Chest

• Abdomen

• Tissues, cells and Juids












Types of donor

• >iving donor

•=eceased donor

• "rgan donors may be living or may have died of brain death or circulatory death Most









• "rgan donors may be living or may have died of brain death or circulatory death. Mostdeceased donors are those who have been pronounced brain dead. Grain dead meansthe cessation of brain function, typically after receiving an in*ury !either traumatic orpathological% to the brain, or otherwise cutting o) blood circulation to the brain !drowning, su)ocation, etc.%. Greathing is maintained via articial sources, which, in turn,maintains heartbeat. "nce brain death has been declared the person can be considered

for organ donation. Criteria for brain death vary. Gecause less than of all deaths inthe L.'. are the result of brain death, the overwhelming ma*ority of deaths are ineligiblefor organ donation, resulting in severe shortages.

• "rgan donation is possible after cardiac death in some situations, primarily when theperson is severely brain in*ured and not e2pected to survive without articial breathingand mechanical support. Independent of any decision to donate, a person1s ne2t-of-+in

may decide to end articial support. If the person is e2pected to e2pire within a shortperiod of time after support is withdrawn, arrangements can be made to withdraw thatsupport in an operating room to allow uic+ recovery of the organs after circulatory deathhas occurred.

• Tissue may be recovered from donors who die of either brain or circulatory death. Ingeneral, tissues may be recovered from donors up to E hours past the cessation of

heartbeat. In contrast to organs, most tissues !with the e2ception of corneas% can bepreserved and stored for up to ve years, meaning they can be ;ban+ed.; Also, morethan 0: grafts may be obtained from a single tissue donor. Gecause of these three factorsHthe ability to recover from a non-heart beating donor, the ability to ban+ tissue, andthe number of grafts available from each donorHtissue transplants are much morecommon than organ transplants. The American Association of Tissue Gan+s estimatesthat more than one million tissue transplants ta+e place in the Lnited 'tates each year.

http://en.wikipedia.org/wiki/Drowning

http://en.wikipedia.org/wiki/Suffocation

http://en.wikipedia.org/wiki/Life_Support

http://en.wikipedia.org/wiki/American_Association_of_Tissue_Banks

http://en.wikipedia.org/wiki/American_Association_of_Tissue_Banks

http://en.wikipedia.org/wiki/Life_Support

http://en.wikipedia.org/wiki/Suffocation

http://en.wikipedia.org/wiki/Drowning



• Li0ing donor• In living donors, the donor remains alive and donates a renewable tissue, cell, or Juid

!e.g., blood, s+in%, or donates an organ or part of an organ in which the remainingorgan can regenerate or ta+e on the wor+load of the rest of the organ !primarilysingle +idney donation, partial donation of liver, lung lobe, small bowel%.#egenerative medicine may one day allow for laboratory-grown organs, usingperson1s own cells via stem cells, or healthy cells e2tracted from the failing organs.

+eceased donor• =eceased donors !formerly cadaveric% are people who have been declared brain-dead

and whose organs are +ept viable by ventilators or other mechanical mechanismsuntil they can be e2cised for transplantation. Apart from brain-stem dead donors, whohave formed the ma*ority of deceased donors for the last : years, there is increasinguse of donation-after-circulatory-death-donors !formerly non-heart-beating donors% toincrease the potential pool of donors as demand for transplants continues to grow.

Prior to the recognition of brain death in the 95D:s, all deceased organ donors haddied of circulatory death. These organs have inferior outcomes to organs from abrain-dead donorB however, given the scarcity of suitable organs and the number ofpeople who die waiting, any potentially suitable organ must be considered.

Allocation of organs

http://en.wikipedia.org/wiki/Medical_ventilator

http://en.wikipedia.org/wiki/Medical_ventilator





Allocation of organs• In most countries there is a shortage of suitable organs for transplantation. Countries often have formal

systems in place to manage the process of determining who is an organ donor and in what order organrecipients receive available organs.

• The overwhelming ma*ority of deceased-donor organs in the Lnited 'tates are allocated by federalcontract to the "rgan Procurement and Transplantation 7etwor+ !"PT7%, held since it was created by the

"rgan Transplant Act of 95DE by the Lnited 7etwor+ for "rgan 'haring or L7"'. !L7"' does not handledonor cornea tissueB corneal donor tissue is usually handled by various eye ban+s.% Individual regionalorgan procurement organiations !"P"s%, all members of the "PT7, are responsible for the identicationof suitable donors and collection of the donated organs. L7"' then allocates organs based on themethod considered most fair by the scientic leadership in the eld. The allocation methodology variessomewhat by organ, and changes periodically. <or e2ample, liver allocation is based partially on M(>=score !Model of (nd-'tage >iver =isease%, an empirical score based on lab values indicative of thesic+ness of the person from liver disease. In 95DE, the 7ational "rgan Transplant Act !7"TA% was passedwhich gave way to the "rgan Procurement and Transplantation 7etwor+ that maintains the organ

registry and ensures euitable allocation of organs. The 'cientic #egistry of Transplant #ecipients wasalso established to conduct ongoing studies into the evaluation and clinical status of organ transplants.In ::: the ChildrenSs 4ealth Act passed and reuired 7"TA to consider special issues around pediatricpatients and organ allocation !'ervices%.

• (2periencing somewhat increased popularity, but still very rare, is directed or targeted donation, inwhich the family of a deceased donor !often honoring the wishes of the deceased% reuests an organ begiven to a specic person. If medically suitable, the allocation system is subverted, and the organ isgiven to that person. In the Lnited 'tates, there are various lengths of waiting times due to the di)erent

availabilities of organs in di)erent L7"' regions. In other countries such as the L , only medical factorsand the position on the waiting list can a)ect who receives the organ.

• "ne of the more publicied cases of this type was the 955E Chester and Patti 'uber transplant. This wasthe rst time that a parent had received a heart donated by one of their own children. Although thedecision to accept the heart from his recently +illed child was not an easy decision, the 'uber familyagreed that giving Patti1s heart to her father would have been something that she would have wanted.Access to organ transplantation is one reason for the growth of medical tourism.


http://en.wikipedia.org/wiki/Organ_Procurement_and_Transplantation_Network

http://en.wikipedia.org/wiki/Organ_Transplant_Act_of_1984


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http://en.wikipedia.org/wiki/UK

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http://en.wikipedia.org/wiki/Organ_Transplant_Act_of_1984

http://en.wikipedia.org/wiki/Organ_Procurement_and_Transplantation_Network




#easons for donation and ethic

al issues• >iving related donors

• Nood 'amaritan

• <inancial compensation• <orced donation

Li0ing related donors• >iving related donors donate to family members or friends in whom they have an emotional investment The ris+ of surgery is















• >iving related donors donate to family members or friends in whom they have an emotional investment. The ris+ of surgery iso)set by the psychological benet of not losing someone related to them, or not seeing them su)er the ill e)ects of waiting on alist.

Paired exchange• =iagram of an e2change between otherwise incompatible pairs

• A ;paired-e2change; is a techniue of matching willing living donors to compatible recipients using serotyping. <or e2ample aspouse may be willing to donate a +idney to their partner but cannot since there is not a biological match. The willing spouse1s

+idney is donated to a matching recipient who also has an incompatible but willing spouse. The second donor must match therst recipient to complete the pair e2change. Typically the surgeries are scheduled simultaneously in case one of the donorsdecides to bac+ out and the couples are +ept anonymous from each other until after the transplant.

• Paired e2change programs were popularied in the 7ew (ngland @ournal of Medicine article ;(thics of a paired-+idney-e2changeprogram; in 9553 by >.<. #oss. It was also proposed by <eli2 T. #apport in 95D0 as part of his initial proposals for live-donortransplants ;The case for a living emotionally related international +idney donor e2change registry; in Transplant Proceedings. Apaired e2change is the simplest case of a much larger e2change registry program where willing donors are matched with anynumber of compatible recipients. Transplant e2change programs have been suggested as early as 953:& ;A cooperative +idneytyping and e2change program.

• The rst pair e2change transplant in the L.'. was in ::9 at @ohns 4op+ins 4ospital. The rst comple2 multihospital +idney

e2change involving 9 person was performed in <ebruary ::5 by The @ohns 4op+ins 4ospital, Garnes-@ewish 4ospital in 't. >ouis and Integris Gaptist Medical Center in "+lahoma City. Another 9-person multihospital +idney e2change was performed fourwee+s later by 'aint Garnabas Medical Center in >ivingston, 7ew @ersey , 7ewar+ Geth Israel Medical Center and7ew Oor+-Presbyterian 4ospital . 'urgical teams led by @ohns 4op+ins continue to pioneer in this eld by having more comple2chain of e2change such as eight-way multihospital +idney e2change. In =ecember ::5, a 9 organ 9 recipient matched +idneye2change too+ place, coordinated through Neorgetown Lniversity 4ospital and 8ashington 4ospital Center, 8ashington =C.

• Paired-donor e2change, led by wor+ in the 7ew (ngland Program for idney (2change as well as at @ohns 4op+ins Lniversity andthe "hio "P"s may more e6ciently allocate organs and lead to more transplants.

http://en.wikipedia.org/wiki/Serotype

http://en.wikipedia.org/wiki/New_England_Journal_of_Medicine

http://en.wikipedia.org/wiki/Johns_Hopkins_Hospital

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http://en.wikipedia.org/wiki/New_England_Journal_of_Medicine

http://en.wikipedia.org/wiki/Serotype



Food %amaritan

• Nood 'amaritan or KaltruisticK donation is giving a donation to someone not well +nown to the donor 'ome people



• Nood 'amaritan or KaltruisticK donation is giving a donation to someone not well-+nown to the donor. 'ome peoplechoose to do this out of a need to donate. 'ome donate to the ne2t person on the listB others use some method ofchoosing a recipient based on criteria important to them. 8eb sites are being developed that facilitate such donation. Ithas been featured in recent television *ournalism that over half of the members of the @esus Christians, an Australian religious group, have donated +idneys in such a fashion.

orced donation

• There have been concerns that certain authorities are harvesting organs from people deem undesirable, such as prison

populations. The 8orld Medical Association stated that prisoners and other individuals in custody are not in a position togive consent freely, and therefore their organs must not be used for transplantation.

• According to the Chinese =eputy Minister of 4ealth, 4uang @iefu, appro2imately 5/ of all organs used for transplantationare from e2ecuted prisoners. The lac+ of public organ donation program in China is used as a *ustication for this practice.

• In @uly ::0, the ilgour-Matas report stated, ;the source of E9,/:: transplants for the si2 year period ::: to ::/ isune2plained; and ;we believe that there has been and continues today to be large scale organ seiures from unwilling<alun Nong practitioners;. Investigative *ournalist (than Nutmann estimates 0/,::: <alun Nong practitioners were +illedfor their organs from ::: to ::D.

• In =ecember ::0, after not getting assurances from the Chinese government about allegations relating to Chineseprisoners, the two ma*or organ transplant hospitals in Uueensland, Australia stopped transplant training for Chinese

surgeons and banned *oint research programs into organ transplantation with China.• In May ::D, two Lnited 7ations 'pecial #apporteurs reiterated their reuests for ;the Chinese government to fully

e2plain the allegation of ta+ing vital organs from <alun Nong practitioners and the source of organs for the suddenincrease in organ transplants that has been going on in China since the year :::;.

• People in other parts of the world are responding to this availability of organs, and a number of individuals !including L.'.and @apanese citiens% have elected to travel to China or India asmedical tourists to receive organ transplants which mayhave been sourced in what might be considered elsewhere to be unethical manner.

Lsage

http://en.wikipedia.org/wiki/Jesus_Christians

http://en.wikipedia.org/wiki/Australia

http://en.wikipedia.org/wiki/Kilgour-Matas_report

http://en.wikipedia.org/wiki/Falun_Gong

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http://en.wikipedia.org/wiki/Ethan_Gutmann

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http://en.wikipedia.org/wiki/Kilgour-Matas_report


http://en.wikipedia.org/wiki/Jesus_Christians

http://en.wikipedia.org/wiki/Organ_transplantation#Usage




Lsage• According to the Council of (urope, 'pain through the 'panish Transplant "rganiation shows

the highest worldwide rate of /.9 donors per million population in ::/ and .D in ::0. In:99, it was /..

• In addition to the citiens waiting for organ transplants in the L.'. and other developednations, there are long waiting lists in the rest of the world. More than million people needorgan transplants in China, /:,::: waiting in >atin America !5: of which are waiting for+idneys%, as well as thousands more in the less documented continent of Africa. =onor basesvary in developing nations.

• Traditionally, Muslims believe body desecration in life or death to be forbidden, and thus manyre*ect organ transplant. 4owever most Muslim authorities nowadays accept the practice ifanother life will be saved.

• In >atin America the donor rate is E:–9:: per million per year, similar to that of developedcountries. 4owever, in Lruguay, Cuba, and Chile, 5: of organ transplants came fromcadaveric donors. Cadaveric donors represent / of donors in 'audi Arabia. There is

continuous e)ort to increase the utiliation of cadaveric donors in Asia, however the popularityof living, single +idney donors in India yields India a cadaveric donor prevalence of less than 9pmp.

• "rgan transplantation in China has ta+en place since the 950:s and China has one of


http://en.wikipedia.org/wiki/Council_of_Europe

http://en.wikipedia.org/wiki/Spain

http://en.wikipedia.org/wiki/Spanish_Transplant_Organization

http://en.wikipedia.org/wiki/Africa

http://en.wikipedia.org/wiki/Africa

http://en.wikipedia.org/wiki/Spanish_Transplant_Organization


http://en.wikipedia.org/wiki/Council_of_Europe


http://en.wikipedia.org/wiki/Organ_transplantation_in_China




• "rgan transplantation in China has ta+en place since the 950:s, and China has one ofthe largest transplant programmes in the world, pea+ing at over 9,::: transplants ayear by ::E. "rgan donation, however, is against Chinese tradition and culture, andinvoluntary organ donation is illegal under Chinese law. China1s transplant programmeattracted the attention of international news media in the 955:s due to ethicalconcerns about the organs and tissue removed from the corpses of e2ecuted criminals

being commercially traded for transplants.

• In ::0 it became clear that about E9,/:: organs had been sourced from <alun Nongpractitioners in China since :::. 8ith regard to organ transplantation in Israel, thereis a severe organ shortage due to religious ob*ections by some rabbis who oppose allorgan donations and others who advocate that a rabbi participate in all decisionma+ing regarding a particular donor. "ne third of all heart transplants performed on

Israelis are done in the Peoples1 #epublic of ChinaB others are done in (urope. =r. @acob>avee, head of the heart-transplant unit, 'heba Medical Center, Tel Aviv, believes that;transplant tourism; is unethical and Israeli insurers should not pay for it. Theorganiation 4"=' !4alachic "rgan =onor 'ociety% is wor+ing to increase +nowledgeand participation in organ donation among @ews throughout the world.

• Transplantation rates also di)er based on race, se2, and income. A study done with

people beginning long term dialysis showed that the sociodemographic barriers torenal transplantation present themselves even before patients are on the transplantlist. <or e2ample, di)erent groups e2press denite interest and complete pretransplantwor+up at di)erent rates. Previous e)orts to create fair transplantation policies hadfocused on people currently on the transplantation waiting list.

( l t ti i di4 t i


http://en.wikipedia.org/wiki/People's_Republic_of_China

http://en.wikipedia.org/wiki/News_media

http://en.wikipedia.org/wiki/Organ_(anatomy)

http://en.wikipedia.org/wiki/Tissue_(biology)

http://en.wikipedia.org/wiki/Organ_transplant

http://en.wikipedia.org/wiki/Organ_transplantation_in_Israel

http://en.wikipedia.org/wiki/Organ_transplantation_in_Israel

http://en.wikipedia.org/wiki/Organ_transplant

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http://en.wikipedia.org/wiki/Organ_(anatomy)

http://en.wikipedia.org/wiki/News_media

http://en.wikipedia.org/wiki/People's_Republic_of_China




(ransplantation o organs in di4erent regions

'idne.1pmp

Li0er1pmp

eart1pmp

L'A / 95 D

(uropa 3 9: E

Africa 99 ./ 9

Asia :. :.:

>atin America 9 9.0 :./

VAll numbers per millionpopulation

+ome e'timate' of the n)m8er of tran'plant' performed in -ario)' region' of the 9orldha-e 8een deri-ed from the .lo8al B)rden of Di'ea'e +t)dy

http://en.wikipedia.org/wiki/Global_Burden_of_Disease_Study




ha-e 8een deri-ed from the .lo8al B)rden of Di'ea'e +t)dy

4istory







4istory• 'uccessful human allotransplants have a relatively long history of operative s+ills that

were present long before the necessities for post-operative survival were discovered.#e*ection and the side e)ects of preventing re*ection !especially infection and

nephropathy% were, are, and may always be the +ey problem.• 'everal apocryphal accounts of transplants e2ist well prior to the scientic

understanding and advancements that would be necessary for them to have actuallyoccurred. The Chinesephysician Pien Chi1ao reportedly e2changed hearts between aman of strong spirit but wea+ will with one of a man of wea+ spirit but strong will in anattempt to achieve balance in each man.#oman Catholic accounts report the rd-century saints =amian and Cosmas as replacing the gangrenous or cancerous leg of the

#oman deacon @ustinian with the leg of a recently deceased(thiopian.D3QDDQ Mostaccounts have the saints performing the transplant in the Eth century, many decadesafter their deathsB some accounts have them only instructing living surgeons whoperformed the procedure.

• The more li+ely accounts of early transplants deal with s+in transplantation. The rstreasonable account is of the Indian surgeon 'ushruta in the nd century GC, who usedautografted s+in transplantation in nose reconstruction, a rhinoplasty. 'uccess or failure

of these procedures is not well documented. Centuries later, the Italian surgeonNasparo Tagliacoi performed successful s+in autograftsB he also failed consistentlywith allografts, o)ering the rst suggestion of re*ection centuries before that mechanismcould possibly be understood. 4e attributed it to the ;force and power of individuality; inhis 9/50 wor+ De Curtorum Chirurgia per Insitionem.

• Ale2is Carrel& 9591s 7obel Prie for his wor+ on organ transplantation.

• The rst successful corneal allograft transplant was performed in 9D3 in a gaelle modelB the rstf l h l t l t + t l ti ti f d b (d d i t


http://en.wikipedia.org/wiki/Allotransplantation

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http://en.wikipedia.org/wiki/Nephropathy

http://en.wikipedia.org/wiki/Transplant_rejection

http://en.wikipedia.org/wiki/Allotransplantation


http://en.wikipedia.org/wiki/Gazelle

http://en.wikipedia.org/wiki/Cornea_transplant

http://en.wikipedia.org/wiki/Eduard_Zirm



http://en.wikipedia.org/wiki/Gazelle



successful human corneal transplant, a +eratoplastic operation, was performed by (duard irm at"lomouc (ye Clinic , now Cech #epublic , in 95:/. The rst transplant in the modern sense – theimplantation of organ tissue in order to replace an organ function – was a thyroid transplant in 9DD. Itwas performed by the 'wiss surgeon and later 7obel laureate Theodor ocher . In the precedingdecades ocher had perfected the removal of e2cess thyroid tissue in cases of goiter to an e2tent thathe was able to remove the whole organ without the person dying from the operation. ocher carried

out the total removal of the organ in some cases as a measure to prevent recurrent goiter. Gy 9DD,the surgeon noticed that the complete removal of the organ leads to a comple2 of particular symptomsthat we today have learned to associate with a lac+ of thyroid hormone. ocher reversed thesesymptoms by implanting thyroid tissue to these perople and thus performed the rst organ transplant.In the following years ocher and other surgeons used thyroid transplantation also to treat thyroiddeciency that appeared spontaneously, without a preceding organ removal. Thyroid transplantationbecame the model for a whole new therapeutic strategy& organ transplantation. After the e2ample ofthe thyroid, other organs were transplanted in the decades around 95::. 'ome of these transplantswere done in animals for purposes of research, where organ removal and transplantation became a

successful strategy of investigating the function of organs. ocher was awarded his 7obel Prie in 95:5for the discovery of the function of the thyroid gland. At the same time, organs were also transplantedfor treating diseases in humans. The thyroid gland became the model for transplants of adrenal andparathyroid glands , pancreas, ovary, testicles and +idney. Gy 95::, the idea that one can successfullytreat internal diseases by replacing a failed organ through transplantation had been generallyaccepted. Pioneering wor+ in the surgical techniue of transplantation was made in the early 95::s bythe <rench surgeonAle2is Carrel , with Charles Nuthrie , with the transplantation of arteries or veins.

Their s+illful anastomosis operations and the new suturing techniues laid the groundwor+ for later

transplantsurgery and won Carrel the 959 7obel Prie in Physiology or Medicine . <rom 95:, Carrelperformed transplant e2periments on dogs. 'urgically successful in moving +idneys, hearts, andspleens, he was one of the rst to identify the problem of re*ection, which remained insurmountable fordecades. The discovery of transplant immunity by the Nerman surgeon Neorg 'chWne , variousstrategies of matching donor and recipient, and the use of di)erent agents for immune suppression didnot result in substantial improvement so that organ transplantation was largely abandoned after 88I.

• Ma*or steps in s+in transplantation occurred during the <irst 8orld 8ar, notably in the wor+ of4arold Nillies at Aldershot Among his advances was the tubed pedicle graft which maintained a



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http://en.wikipedia.org/w/index.php?title=Georg_Sch%C3%B6ne&action=edit&redlink=1

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http://en.wikipedia.org/wiki/Germany

http://en.wikipedia.org/wiki/Transplant_Rejection

http://en.wikipedia.org/wiki/Spleen


http://en.wikipedia.org/wiki/Kidney

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http://en.wikipedia.org/wiki/Vein

http://en.wikipedia.org/wiki/Artery

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http://en.wikipedia.org/wiki/Testicle

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http://en.wikipedia.org/wiki/Parathyroid_gland

http://en.wikipedia.org/wiki/Adrenal_gland

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http://en.wikipedia.org/wiki/Goiter

http://en.wikipedia.org/wiki/Theodor_Kocher

http://en.wikipedia.org/wiki/Nobel_laureate

http://en.wikipedia.org/wiki/Switzerland

http://en.wikipedia.org/wiki/Thyroid


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http://en.wikipedia.org/wiki/Skin_transplant

http://en.wikipedia.org/wiki/Harold_Gillies

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http://en.wikipedia.org/wiki/Skin_transplant



4arold Nillies at Aldershot. Among his advances was the tubed pedicle graft, which maintained aJesh connection from the donor site until the graft established its own blood Jow. Nillies1assistant, Archibald McIndoe , carried on the wor+ into the 'econd 8orld 8ar asreconstructive surgery . In 950, the rst successful replantation surgery was performed – re-attaching a severed limb and restoring !limited% function and feeling.

• Transplant of a single gonad !testis% from a living donor was carried out in early @uly 950 in

a*eXar, 'erbia, by a #ussian emigrY surgeon =r. Peter ?asil1eviX olesni+ov. The donor was aconvicted murderer, one Ili*a ra*an, whose death sentence was commuted to : yearsimprisonment, and he was led to believe that it was done because he had donated his testis to anelderly medical doctor. Goth the donor and the receiver survived, but charges were brought in acourt of law by the public prosecutor against =r. olesni+ov, not for performing the operation, butfor lying to the donor.5:Q

• The rst attempted human deceased-donor transplant was performed by the L+rainian surgeon Ouri ?oronoy in the 95:sB59Q5Q re*ection resulted in failure. @oseph Murray and @. 4artwell 4arrison performed the rst successful transplant, a +idney transplant between identical twins, in 95/E,because no immunosuppression was necessary for genetically identical individuals.

• In the late 95E:s Peter Medawar , wor+ing for the 7ational Institute for Medical #esearch ,improved the understanding of re*ection. Identifying the immune reactions in 95/9, Medawarsuggested that immunosuppressive drugs could be used. Cortisone had been recently discoveredand the more e)ective aathioprine was identied in 95/5, but it was not until the discovery ofcyclosporine in 953: that transplant surgery found a su6ciently powerful immunosuppressive.

• @oseph Murray1s success with the +idney led to attempts with other organs. There was asuccessful deceased-donor lung transplant into a lung cancer su)erer in @une 950 by @ames 4ardyin @ac+son, Mississippi . The person survived for eighteen days before dying of+idney failure. Thomas 'tarl of =enver attempted a liver transplant in the same year, but he wasnot successful until 9503.



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http://en.wikipedia.org/wiki/Ciclosporin

http://en.wikipedia.org/wiki/Lung

http://en.wikipedia.org/wiki/Lung_cancer

http://en.wikipedia.org/wiki/James_Hardy_(surgeon)

http://en.wikipedia.org/wiki/Jackson,_Mississippi

http://en.wikipedia.org/wiki/Kidney_failure

http://en.wikipedia.org/wiki/Thomas_Starzl

http://en.wikipedia.org/wiki/Denver

http://en.wikipedia.org/wiki/Denver


http://en.wikipedia.org/wiki/Kidney_failure

http://en.wikipedia.org/wiki/Jackson,_Mississippi

http://en.wikipedia.org/wiki/James_Hardy_(surgeon)

http://en.wikipedia.org/wiki/Lung_cancer

http://en.wikipedia.org/wiki/Lung

http://en.wikipedia.org/wiki/Ciclosporin

http://en.wikipedia.org/wiki/Azathioprine

http://en.wikipedia.org/wiki/Cortisone

http://en.wikipedia.org/wiki/Immunosuppressive_drug

http://en.wikipedia.org/wiki/National_Institute_for_Medical_Research

http://en.wikipedia.org/wiki/Peter_Medawar

http://en.wikipedia.org/wiki/Immunosuppression

http://en.wikipedia.org/wiki/Twin

http://en.wikipedia.org/wiki/J._Hartwell_Harrison

http://en.wikipedia.org/wiki/Joseph_Murray


http://en.wikipedia.org/w/index.php?title=Yuri_Voronoy&action=edit&redlink=1

http://en.wikipedia.org/wiki/Ukraine


http://en.wikipedia.org/wiki/Emigr%C3%A9

http://en.wikipedia.org/wiki/Russians

http://en.wikipedia.org/wiki/Serbia

http://en.wikipedia.org/wiki/Zaje%C4%8Dar

http://en.wikipedia.org/wiki/Gonad

http://en.wikipedia.org/wiki/Reconstructive_surgery

http://en.wikipedia.org/wiki/World_War_II

http://en.wikipedia.org/wiki/Archibald_McIndoe

http://en.wikipedia.org/wiki/Blood





(imeline o successul transplants• 9D& <irst s+in autograft-transplantation of s+in tissue from one location on an individual1s body to another location !Nermany% In 9D Carl



pg p y ! y%Gunger, a Nerman surgeon documents the rst modern successful s+in graft on a person. Gunger was repairing a person with a nose alsodestroyed by syphilis . 4e grafted a small chun+ of full thic+ness Jesh from the inner thigh to the nose successfully, in a method veryreminiscent of 'ushruthaSs.

• 95:/& <irst successful cornea transplant by (duard irm !Cech #epublic %

• 95:D& <irst s+in allograft-transplantation of s+in from a donor to a recipient !'witerland%

• 95& <irst successful cadaveric AG-: incompatible +idney transplant !donor was G!III% and the recipient has :!I%% by Ouriu Ou. ?oronoy !L''#%

• 95/:& <irst successful +idney transplant by =r. #ichard 4. >awler !Chicago, L.'.A.%

•95/E& <irst living related +idney transplant !identical twins % !L.'.A.%• 95//& <irst heart valve allograft into descending aorta !Canada%

• 950& <irst +idney transplant from a deceased donor !L.'.A.%

• 950/& Australia 1s rst successful !living% +idney transplant !Uueen (liabeth 4ospital , 'A, Australia%

• 9500& <irst successful pancreas transplant by #ichard >illehei and 8illiam elly !Minnesota, L.'.A.%

• 9503& <irst successful liver transplant by Thomas 'tarl !=enver, L.'.A.%

• 9503& <irst successful heart transplant by Christian Garnard !Cape Town, 'outh Africa%

• 95D9& <irst successful heart$lung transplant by Gruce #eit !'tanford, L.'.A.%

• 95D& <irst successful lung lobe transplant by @oel Cooper at the Toronto Neneral 4ospital ! Toronto, Canada%

• 95DE& <irst successful double organ transplant by Thomas 'tarl and 4enry T. Gahnson !Pittsburgh, L.'.A.%

• 95D0& <irst successful double-lung transplant !Ann 4arrison% by @oel Cooper at the Toronto Neneral 4ospital !Toronto, Canada%

• 955/& <irst successful laparoscopic live-donor nephrectomy by >loyd #atner and >ouis avoussi !Galtimore, L.'.A.%

• 9553& <irst successful allogeneic vascularied transplantation of a fresh and perfused human +nee *oint by Nunther ". 4ofmann

• 9553& Illinois1 rst living donor +idney-pancreas transplant and rst robotic living donor pancreatectomy in the L.'.A.Lniversity of Illinois Medical Center

• 955D& <irst successful live-donor partial pancreas transplant by =avid 'utherland !Minnesota, L.'.A.%

• 955D& <irst successful hand transplant by =r. @ean-Michel =ubernard !>yon, <rance%

• 955D& Lnited 'tates1 rst adult-to-adult living donor liver transplant Lniversity of Illinois Medical Center

• 9555& <irst successful tissue engineered bladder transplanted by Anthony Atala !Goston Children1s 4ospital , L.'.A.%

• :::& <irst robotic donor nephrectomy for a living-donor +idney transplant in the world Lniversity of Illinois Medical Center

• ::E& <irst liver and small bowel transplants from same living donor into same recipient in the world Lniversity of Illinois Medical Center

• ::/& <irst successful ovarian transplant by =r. P. 7. Mhatre !8adia 4ospital, Mumbai, India%

• ::/& <irst successful partial face transplant !<rance%

http://en.wikipedia.org/wiki/Skin_graft

http://en.wikipedia.org/wiki/Syphilis

http://en.wikipedia.org/wiki/Sushrutha



http://en.wikipedia.org/wiki/Chicago

http://en.wikipedia.org/wiki/Identical_twins

http://en.wikipedia.org/wiki/Heart_valve

http://en.wikipedia.org/wiki/Aorta

http://en.wikipedia.org/wiki/Canada


http://en.wikipedia.org/wiki/Queen_Elizabeth_Hospital,_Adelaide

http://en.wikipedia.org/wiki/South_Australia

http://en.wikipedia.org/wiki/Minnesota


http://en.wikipedia.org/wiki/Christian_Barnard

http://en.wikipedia.org/wiki/Bruce_Reitz

http://en.wikipedia.org/wiki/Joel_D._Cooper

http://en.wikipedia.org/wiki/Toronto_General_Hospital

http://en.wikipedia.org/wiki/Toronto


http://en.wikipedia.org/wiki/Pittsburgh

http://en.wikipedia.org/wiki/Ann_Harrison_(lung_transplant_recipient)



http://en.wikipedia.org/wiki/Laparoscopic_surgery

http://en.wikipedia.org/wiki/Baltimore

http://en.wikipedia.org/wiki/Knee

http://en.wikipedia.org/wiki/Gunther_O._Hofmann


http://en.wikipedia.org/wiki/Pancreas_transplant

http://en.wikipedia.org/wiki/Jean-Michel_Dubernard

http://en.wikipedia.org/wiki/Lyon


http://en.wikipedia.org/wiki/Bladder

http://en.wikipedia.org/wiki/Anthony_Atala

http://en.wikipedia.org/wiki/Boston_Children's_Hospital





http://en.wikipedia.org/wiki/Boston_Children's_Hospital

http://en.wikipedia.org/wiki/Anthony_Atala

http://en.wikipedia.org/wiki/Bladder


http://en.wikipedia.org/wiki/Lyon

http://en.wikipedia.org/wiki/Jean-Michel_Dubernard

http://en.wikipedia.org/wiki/Pancreas_transplant


http://en.wikipedia.org/wiki/Gunther_O._Hofmann

http://en.wikipedia.org/wiki/Knee

http://en.wikipedia.org/wiki/Baltimore

http://en.wikipedia.org/wiki/Laparoscopic_surgery



http://en.wikipedia.org/wiki/Ann_Harrison_(lung_transplant_recipient)

http://en.wikipedia.org/wiki/Pittsburgh


http://en.wikipedia.org/wiki/Toronto



http://en.wikipedia.org/wiki/Bruce_Reitz

http://en.wikipedia.org/wiki/Christian_Barnard


http://en.wikipedia.org/wiki/Minnesota

http://en.wikipedia.org/wiki/South_Australia

http://en.wikipedia.org/wiki/Queen_Elizabeth_Hospital,_Adelaide


http://en.wikipedia.org/wiki/Canada

http://en.wikipedia.org/wiki/Aorta

http://en.wikipedia.org/wiki/Heart_valve

http://en.wikipedia.org/wiki/Identical_twins

http://en.wikipedia.org/wiki/Chicago



http://en.wikipedia.org/wiki/Sushrutha

http://en.wikipedia.org/wiki/Syphilis

http://en.wikipedia.org/wiki/Skin_graft

http://en.wikipedia.org/wiki/Mumbai


http://en.wikipedia.org/wiki/Face_transplant





http://en.wikipedia.org/wiki/Mumbai



::/& <irst successful partial face transplant !<rance%

• ::/& <irst robotic hepatectomy in the Lnited 'tates Lniversity of Illinois Medical Center

• ::0& Illinois1 rst paired donation for AG" incompatible +idney transplant Lniversity of Illinois Medical Center

• ::0& <irst *aw transplant to combine donor *aw with bone marrow from the patient, by (ric M. Nenden !Mount 'inai 4ospital, 7ew Oor+ City, L.'.A.%

• ::0& <irst successful human penis transplant !later reversed after 9/ days due to EE-year-old recipient1s wife1s

psychological re*ection% !Nuanghou, China%• ::D& <irst successful complete full double arm transplant by (dgar Giemer, Christoph 4Whn+e and Manfred

'tangl ! Technical Lniversity of Munich, Nermany%

• ::D& <irst baby born from transplanted ovary. The transplant was carried out by =r 'herman 'ilber at theInfertility Centre of 't >ouis in Missouri. The donor is her twin sister.

• ::D& <irst transplant of a human windpipe using a patient1s own stem cells, by Paolo Macchiarini !Garcelona,'pain%

• ::D& <irst successful transplantation of near total area !D:% of face, !including palate, nose, chee+s, and eyelid%by Maria 'iemionow !Cleveland Clinic, L.'.A.%

• ::5& 8orlds1 rst robotic +idney transplant in an obese patient Lniversity of Illinois Medical Center

• :9:& <irst full facial transplant by =r. @oan Pere Garret and team !4ospital Lniversitari ?all d14ebron on 0 @uly:9:, in Garcelona, 'pain%

• :99& <irst double leg transplant by =r. Cavadas and team !?alencia1s 4ospital, >a <e, 'pain%

• :9& <irst #obotic Alloparathyroid transplant. Lniversity of Illinois Chicago

• :9& <irst successful entire face transplantation as an urgent life-saving surgery atMaria '+Zodows+a-Curie Institute of "ncology branch in Nliwice, Poland.

• :9E& <irst successful uterine transplant resulting in live birth !'weden%

• :9E& <irst successful penis transplant. !'outh Africa%• :9E& <irst neonatal organ transplant. !L..%

'ociety and culture





http://en.wikipedia.org/wiki/Jaw


http://en.wikipedia.org/wiki/Bone_marrow

http://en.wikipedia.org/wiki/Eric_M._Genden

http://en.wikipedia.org/wiki/Mount_Sinai_Hospital,_New_York

http://en.wikipedia.org/wiki/New_York_City

http://en.wikipedia.org/wiki/Penis

http://en.wikipedia.org/wiki/Guangzhou


http://en.wikipedia.org/wiki/Arm

http://en.wikipedia.org/wiki/Technical_University_of_Munich

http://en.wikipedia.org/wiki/Vertebrate_trachea

http://en.wikipedia.org/wiki/Paolo_Macchiarini

http://en.wikipedia.org/wiki/Barcelona



http://en.wikipedia.org/wiki/Palate

http://en.wikipedia.org/wiki/Nose

http://en.wikipedia.org/wiki/Cheeks

http://en.wikipedia.org/wiki/Eyelid

http://en.wikipedia.org/wiki/Maria_Siemionow

http://en.wikipedia.org/wiki/Cleveland_Clinic




http://en.wikipedia.org/wiki/Curie_Institute,_Warsaw

http://en.wikipedia.org/wiki/Gliwice

http://en.wikipedia.org/wiki/Poland

http://en.wikipedia.org/wiki/Poland

http://en.wikipedia.org/wiki/Gliwice

http://en.wikipedia.org/wiki/Curie_Institute,_Warsaw




http://en.wikipedia.org/wiki/Cleveland_Clinic

http://en.wikipedia.org/wiki/Maria_Siemionow

http://en.wikipedia.org/wiki/Eyelid

http://en.wikipedia.org/wiki/Cheeks

http://en.wikipedia.org/wiki/Nose

http://en.wikipedia.org/wiki/Palate




http://en.wikipedia.org/wiki/Paolo_Macchiarini

http://en.wikipedia.org/wiki/Vertebrate_trachea

http://en.wikipedia.org/wiki/Technical_University_of_Munich

http://en.wikipedia.org/wiki/Arm


http://en.wikipedia.org/wiki/Guangzhou

http://en.wikipedia.org/wiki/Penis

http://en.wikipedia.org/wiki/New_York_City

http://en.wikipedia.org/wiki/Mount_Sinai_Hospital,_New_York

http://en.wikipedia.org/wiki/Eric_M._Genden

http://en.wikipedia.org/wiki/Bone_marrow











'ociety and culture

• Comparative costs

• 'afety

• Transplant laws

• (thical concerns

• Articial organ transplantation















(ransplant las• Goth developing and developed countries have forged various policies to try to increase the safety and



• Goth developing and developed countries have forged various policies to try to increase the safety andavailability of organ transplants to their citiens. Austria, Grail, <rance, Italy, Polandand 'pain haveruled all adults potential donors with the ;opting out; policy, unless they attain cards specifying not tobe. 4owever, whilst potential recipients in developing countries may mirror their more developedcounterparts in desperation, potential donors in developing countries do not. The Indian government has had di6culty trac+ing the Jourishing organ blac+ mar+et in their country, but in recent times it has

amended its organ transplant law to ma+e punishment more stringent for commercial dealings inorgans. It has also included new clauses in the law to support deceased organ donation, such as ma+ingit mandatory to reuest for organ donation in case of brain death. "ther countries victimied by illegalorgan trade have also implemented legislative reactions. Moldova has made internationaladoption illegal in fear of organ tra6c+ers. China has made selling of organs illegal as of @uly ::0 andclaims that all prisoner organ donors have led consent. 4owever, doctors in other countries, such asthe Lnited ingdom, have accused China of abusing its high capital punishment rate. =espite thesee)orts, illegal organ tra6c+ing continues to thrive and can be attributed to corruption in healthcaresystems, which has been traced as high up as the doctors themselves in China and L+raine, and theblind eye economically strained governments and health care programs must sometimes turn to organtra6c+ing. 'ome organs are also shipped to Lganda and the 7etherlands. This was a main product inthe triangular trade in 95E.

• 'tarting on 9 May ::3, doctors involved in commercial trade of organs will face nes and suspensionsin China. "nly a few certied hospitals will be allowed to perform organ transplants in order to curbillegal transplants. 4arvesting organs without donor1s consent was also deemed a crime.

• "n 3 @une ::D, Indonesian, 'ulaiman =amani+, 0, pleaded guilty in 'ingapore court for sale of his+idney to C Tang1s e2ecutive chair, Tang 8ee 'ung, //, for 9/: million rupiah!'[,::%. The

Transplant (thics Committee must approve living donor +idney transplants. "rgan trading is banned in'ingapore and in many other countries to prevent the e2ploitation of ;poor and socially disadvantageddonors who are unable to ma+e informed choices and su)er potential medical ris+s.; Toni, 3, the otheraccused, donated a +idney to an Indonesian patient in March, alleging he was the patient1s adoptedson, and was paid 9D0 million rupiah !:,::L'=%. Lpon sentence, both would su)er each, 9 monthsin *ail or 9:,::: 'ingapore dollars!3,0:: L'=% ne.

• In an article appearing in the April ::E issue of (con @ournal 8atch, economist Ale2Tabarro+ e2amined the impact of direct consent laws on transplant organ availability Tabarro+

http://en.wikipedia.org/wiki/Austria

http://en.wikipedia.org/wiki/Health_in_Brazil

http://en.wikipedia.org/wiki/Health_in_France

http://en.wikipedia.org/wiki/Health_in_Italy

http://en.wikipedia.org/wiki/Health_in_Poland

http://en.wikipedia.org/wiki/Health_in_Spain

http://en.wikipedia.org/wiki/Indian_government

http://en.wikipedia.org/w/index.php?title=Adoption_in_Moldova&action=edit&redlink=1

http://en.wikipedia.org/w/index.php?title=Adoption_in_Moldova&action=edit&redlink=1

http://en.wikipedia.org/wiki/Indian_government

http://en.wikipedia.org/wiki/Health_in_Spain

http://en.wikipedia.org/wiki/Health_in_Poland

http://en.wikipedia.org/wiki/Health_in_Italy

http://en.wikipedia.org/wiki/Health_in_France

http://en.wikipedia.org/wiki/Health_in_Brazil

http://en.wikipedia.org/wiki/Austria



Tabarro+ e2amined the impact of direct consent laws on transplant organ availability. Tabarro+found that social pressures resisting the use of transplant organs decreased over time as theopportunity of individual decisions increased. Tabarro+ concluded his study suggesting thatgradual elimination of organ donation restrictions and move to a free mar+et in organ sales willincrease supply of organs and encourage broader social acceptance of organ donation as apractice.

&thical concerns• The e2istence and distribution of organ transplantation procedures in developing countries, while

almost always benecial to those receiving them, raise many ethical concerns. Goth the sourceand method of obtaining the organ to transplant are ma*or ethical issues to consider, as well asthe notion of distributive *ustice. The 8orld 4ealth "rganiation argues that transplantationspromote health, but the notion of ;transplantation tourism; has the potential to violate humanrights or e2ploit the poor, to have unintended health conseuences, and to provide uneual

access to services, all of which ultimately may cause harm. #egardless of the ;gift of life;, in theconte2t of developing countries, this might be coercive. The practice of coercion could beconsidered e2ploitative of the poor population, violating basic human rights according to Articles and E of the Lniversal =eclaration of 4uman #ights. There is also a powerful opposing view,that trade in organs, if properly and e)ectively regulated to ensure that the seller is fully informedof all the conseuences of donation, is a mutually benecial transaction between two consentingadults, and that prohibiting it would itself be a violation of Articles and 5 of the Lniversal=eclaration of 4uman #ights.

• (ven within developed countries there is concern that enthusiasm for increasing the supply oforgans may trample on respect for the right to life. The uestion is made even more complicatedby the fact that the ;irreversibility; criterion for legal death cannot be adeuately dened and caneasily change with changing technology.

Artifcial organ transplantation• 'urgeons in 'weden performed the rst implantation of a synthetic trachea in @uly :99, for a 0-

year old patient who was su)ering from cancer 'tem cells ta+en from the patient1s hip were

Curs 6, 7, 8 Imunologia Transplantului

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Transcript of Curs 6, 7, 8 Imunologia Transplantului