Transcript Neoplasm (melanoma) risk in transplant patients

The role of immunosuppression
and sunlight exposure in cancer
formation with post-renal
transplant patients
By: Amanda Stevens
Advisor: Dr. Boissonneault
Overview
• Why is this important to me?
• Why should this be important to you?
• Many people in our communities are
immune compromised.
• Immune suppression does not
discriminate.
Why and How to Immunosuppress?
• One way of becoming immune compromised
is by receiving a transplant and then being
treated with immunosuppressant drugs to
prevent allograft rejection.
• These drugs can give you one of three
outcomes:
– Therapeutic effect
– Undesired consequences of
immunodeficiency
– Nonimmune toxicity to other tissues
Undesired consequences of
immunodeficiency
• All of the immunosuppressant drugs
interfere with body’s ability to survey and
destroy tumor cells.
• This leads to an unchecked balance in the
body which can produce tumors and
cancers.
• One specific cancer that kidney transplant
recipients encounter frequently are skin
cancers.
27% of deaths occurring
at least 4 years post
transplantation were
caused by skin cancer!
At 20 years post transplantation, cancer
incidence is estimated to be 70% for
renal transplant recipients!
This is your natural immune system
Types of immunosuppressant
drugs given to RTRs
• Grouped according to their MOA
• Cyclosporine and Tacrolimus
– Calcineurin inhibitors
– A little over 20 years old
• Mycophenolate Mofetil [MMF] (CellCept®)
– Since 1995
– Reversible inhibitor of the enzyme inosine
monophosphate dehydrogenase (IMPDH)
Types of immunosuppressant
drugs given to RTRs
• Sirolimus and Everolimus
– “TOR” Inhibitors
– Blocks proliferation
• Azathioprine
– Use started more than 30 years ago
– Incorporates itself into DNA
– Broad myelocyte suppressant
Types of immunosuppressant
drugs given to RTRs
• Corticosteroids
– Introduced to the transplant community in the
1960’s
– Inhibits the expression cytokines such as:
IL-1, IL-2, IL-3, IL-6, TNF-ά, and γ-interferon.
• Monoclonal and Polyclonal Antibodies
– OKT3 (Monoclonal) – IgG
– Humanized anti-CD25 Monoclonal Ab (Basiliximab
and Daclizumab)
– Atgam (Polyclonal) replaced by Thymoglobulin
preparations.
• New drugs on the way!!!!
• Studies have tried to prove….
This is your immune system on
drugs…immunosuppressants that is
To sum up the drugs…
• Berg and Otley did a study and the paper
it produced said:
– First, agents used during transplantation
themselves may be carcinogenic
– Second, by having chronic
immunesuppression this creates a state in
which natural surveillance and eradication of
precancerous transformations are hindered!
Types of cancers found in RTR
• Some do not occur at an elevated
rate: breast, colon, lung, and
prostate.
• Some ARE elevated including:
esophagus, skin, liver, cervix,
bladder, thyroid, and renal cells.
• Focusing now on skin!
Types of cancers found in RTR
General Population
Renal Transplant
Recipients
Breast, colon, lung, and
prostate
Esophagus, skin, liver,
cervix, bladder, thyroid,
and renal cells
Basal Cell Carcinoma
BCC>SCC at 2-4:1
Squamous Cell Carcinoma
SCC>BCC at 3:2
Melanoma, Kaposi’s
sarcoma, Merkel cell
carcinoma
Locations of cancer
• SCC and BCC are normally found on
constantly sun exposed areas:
–Temples, forhead, lips, auricles,
neck, and upper extremities.
Things can look benign….
A squamous cell
carcinoma in an
RTR.
http://www.captaincutaneum.com/science/squamous/images/squamous_01.jpg
…or really bad…
http://www.lib.uiowa.edu/hardin/md/pictures22/
dermnet/21_basal_cell_carcinoma_cancer_imi
quimod0822057.jpg (top right)
http://www.imr.gov.my/org/CRC/slide57f.jpg
(bottom right)
http://www.aad.org/education/students/_i
mg/ActinicKerNoMelCancer13.jpg (left)
Risk factors for cancer
• No single factor can be pinpointed.
• Having multiple risk factors will increase the
incidence of skin cancers.
• Risk factors include:
– Being an older pt
– Duration of immunosuppression
– Male
– Earlier age of transplantation
– Higher dose of immunosuppresion
– Genetic predispositions
– Having skin types I, II, or II on Fitzpatrick scale
– Significant exposure to UV radiation
– HPV infection
– Lower CD4+ cell counts naturally
Quick Stats
• Only 54% of renal transplant patients even
remember getting advice on staying out of the
sun.
• Of those 54%, only 30% knew why it was
important.
• 27% of deaths occurring at least 4 years post
transplantation were caused by skin cancer!
• The average post-transplant neoplasm appears
on average at approximately 5 years.
• Only 5.6% of RTRs used sunscreen on a
consistent basis prior to transplantation.
• That number only increased to 36.7% after
transplantation.
What we can do to help!
• Education
–
–
–
–
Avoid sun exposure
Use sunscreens
Cover up
Avoid “peak hours” (10a-4p)
• Team approach
• Primary prevention
– Screenings (tumor markers, Immunoknow Assay,
sCD30)
• Early intervention
In conclusion!
• Educate ourselves!
• Educate our pts!
Thanks for your attention!
Thanks Dr. B!
References
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Berg D, Otley CC. Skin cancer in organ transplant recipients: epidemiology, pathogenesis, and
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