GVHD(M.Abdullah)

8/8/2019 GVHD(M.Abdullah)

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Graft vs. Host

Disease

(GVHD)

Prepared by : Muhammad Abdullah3rd Year MBBS

Batch#15Roll#22



Transplantation:

To transfer (an organ, tissue, etc.) from one part of the

body to another (Auto graft) or from one person or animal

to another (Allograft).



Steps:

Histocompatibility of Donor

Suppression of host immune system

Replacement

Clinical supervision (e.g. to make sure the

accommodation of graft , to inhibit infections , etc)



Examples of Transplantation: K idney transplant

Corneal transplant

Bone marrow transplant

Coronary artery bypass

Liver transplantation

etc.



Graft:

A portion of living tissue sur gically tra ns pla nted fr om

one part of a n individual to a nother, or fr om one

individual to a nother, f or its adhesion a nd gr owth.

E.g.: Cor neal graft, Skin graft , etc



Use of Grafting:

Cosmetic use (e.g. skin grafting)

To inhibit a tissue Damage (e.g. coronary artery bypass)

To replace a damaged part (e.g. corneal grafting)

To treat malignant or non-malignant conditions (e.g. bone

marrow transplantation )



Graft vs. Host Disease(GVHD):

Graft-versus-host disease (GVHD) is a common

complication of allogenic bone marrow transplantation

in which functional immune cells in the transplanted

marrow recognize the recipient as "foreign" and mount

an immunologic attack.



Causes:1) Non-histocompatible transplantation

2) Over immuno-suppression of recipient



Pathogenesis:

T-cells of allograft take host as foreign

T-cells of graft attack the host tissues

Secrete excess of cytokines including TNF-, INF- & IL-2

CD4+ T cells are crucial for sustaining the secondary

expansion of CD8+ T cells



Interaction of factors involved in graft versus host disease (GVHD).Cytokines, such as interleukin-2, tumor necrosis factor-alpha, andgamma interferon, play an important role in the initiation andpropagation of GVHD.





SkinMost often involvedMaculopapular rashPalms and soles initially

LiverH yper-bilirubinemia and increased alkaline phosphatase

GIManifests as diarrhea

Upper GI symptoms - nausea, anorexiaSevere cases - ileus, cramping pain, bleeding

Upper GI tract / oral mucosaRenal (rarely)Eye



F orms of GVHD:

1- H yper Acute Graft vs. Host Disease (haGVHD)2- AcuteGraft vs. Host Disease (aGVHD)

3- Chronic Graft vs. Host Disease (cGVHD)



Hyper Acute GVHD:

Takes place just after the transplantation within minutes

Can be appreciated by the surgeon within some minutesafter the transplantation

Can last up to 24 hours

Can even cause death of the organ



Causes of Hyper Acute GVHD:Preformed antidonor antibodies

In multiparous women, anti-HLA antibodies against paternal

Prior blood transfusion can also lead presensitization

*H yper Acute GVHD is no more significant clinical problem



Acute (aGVHD):

Normally observed within the first 100 days post-transplant

After the hyper acute phaseMajor challenge to transplants owing to associated

morbidity and mortality.

Selective damage to the liver, skin and mucosa ,GIT &

hematopoietic system (e.g. bone marrow and thymus)

Cellular and humoral response



Predictors of acute GVHD:HLA disparitiesIncreasing age (>40)

Gender mismatch / parity of donorMinor histo-compatibility antigensCD34 doseT-cell depletion in host Advanced disease status



Skin rash

Diarrhea

Abnormal liver function

Increased susceptibility to infection

Symptoms usually begin within 2 months after

transplantation





Skin biopsy in acute GVHD:



Acute graf t versus host disease. Tissue stained w ithhematoxylin and eosin show s dy sk eratosis of indi v idualk eratinocy tes and patchy vacuolization of the basement membrane. A moderate superf icial dermal and peri vascularlymphocy tic inf iltrate is also seen.



Skin Biopsy in Acute GVHD



R ectal biops y:



Acute graft versus host disease involvingdesquamating skin lesions in a patient whounderwent allogeneic bone marrowtransplantation for myelodysplasia.



Boy who developed stage 3 skin involvement with acute

graft versus host disease (GVHD).The donor was a sistermatched for human leukocyte antigen.



Chronic (cGVHD):

Normally occurs after 100 days

Along with liver, skin, GIT, hematopoietic system, also

causes damage to the connective tissue and exocrine glands.



Skin rash

Dermatitis

Hair loss

Liver damage

Dry eyes and dry mouth

Increased susceptibility to infections

Possibly lung and gastrointestinal disorders

Chronic symptoms start more than 3 months after

transplant.



Prior acute GVHD

Older donor/recipient age

HLA mismatch V iral infection (e.g., cytomegalovirus)

Splenectomy





Scleroderma causingnail dystrophy.

cGVHD



Oral mucosal changes in a patient with chronic

graft versus host disease (GVHD). Note the skindiscoloration (vitiligo), which can result from

GVHD.



Boy in whom graft versus host disease (GVHD), which progressed to stage

4. High-dose cyclosporine A and methylprednisolone had beenadministered intravenously. The patient later died from chronicpulmonary disease resulting from chronic GVHD.



Primary Treatment: Disrupt the triad Non-specific Immunosuppressive

methylpred 2mg/kg/day Steroid + calcineurin inhibitor (CSA, tacro)

~40% of sib transplants and 24% of MUDs willrespond to steroids R esponse is worse w ith li ver in volvement and w ith

higher grade



Secondary Therapy

Target the IL-2 receptors

No secondary therapy to date provides notable resultsFocus remains on prevention and prediction



Conclusion:

GVHD is the major barrier to successful allogenic stem cell

transplantationThis may be avoided by:More precise matchingOptimum immunosupressing



A costless medicinehaving effects independent of

receptors, therapeutic index,clinical sign & symptoms andhaving no side-effects at all«

So,

Use it!!



*for not sleeping ;-)

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GVHD(M.Abdullah)