The document discusses post-transplant malignancies in solid organ transplant recipients. It notes that recipients have a 3-5 fold higher risk of cancer than the general population due to prolonged immunosuppression. The most common post-transplant malignancies are non-melanoma skin cancer, post-transplant lymphoproliferative disorder (PTLD), and Kaposi's sarcoma. PTLD is often associated with Epstein-Barr virus infection and occurs more frequently after transplants of certain organs. Treatment involves reducing immunosuppression when possible and additional therapies depending on the malignancy type and individual case.

1. POST TRANSPLANT MALIGNANCY – A
BRIEF REVIEW

2. Review Article
INTRODUCTION
Solid organs transplant is the only life saving modality
for end stage disease of various organs. In past few decades
great advances have been made in the field of organ
transplant.Availabilityofexcellentinfrastructureinleading
hospitals, advancement of surgical techniques, growing
research and development of various safe options for
immunosuppression have lead to improvement in graft
survival, increased life expectancy and morbidity free post
transplant life in recipients. This has resulted in notable
increase in number of solid organ transplants. Currently
survival rate of renal transplant recipients is 95% at 1 year
and about 90% at 5 years [1].
Recipients of solid organ transplant are exposed to
prolonged immunosuppression which increases potential
risk of post transplant malignancies (PTM). In addition,
relatively older individuals are being considered for
transplants who carry inherent risk of malignancies. Thus
PTM is now a major challenge in patients successfully
treated by organ transplantation. Compared to general
population, several types of malignancies occur more
commonly in transplant recipients and are often more
aggressive with far worse prognosis [2].
In 1968, Starzl and Penn described the first case of Post
Transplant Lymphoproliferative Disorder (PTLD). Penn
established a voluntary Transplant Tumor Registry in 1969,
which was posthumously renamed as Israel Penn
InternationalTransplantTumorregistry(IPITTR)inhonour
of his life’s commitment to the study of transplant
malignancies [3].
INCIDENCE
Immunosuppressed allograft organ recipients have 3 to
5 fold increase in cancer risk as compared to age matched
general population [4]. The most common malignancies
encounteredinposttransplantrecipientsarenonmelanotic
skin cancers (NMSC - upto 82 %), PTLD (upto 11%) and
Kaposi’s sarcoma (KS) (about 6%) [5-7]. Besides these
malignancies, other tumors showing higher frequency are
renal cell carcinoma, in-situ carcinoma of uterine cervix,
hepatobiliary carcinoma, anogential cancer and
gastrointestinal tumors [8]. US Renal Data System
(USRDS) database showed that incidence of common
cancerssuchascolon,lung,prostateand breastistwotimes
higher in post transplant recipients as compared to age
matchedpopulation,whiletheincreaseinincidenceranges
from 3 fold for bladder and testicular malignancies, 15 fold
for kidney malignancies and 20 fold for lymphomas and
NMSC [9].
Netherland study showed that skin malignancy
developedin53%ofpatientsafterrenaltransplantand48%
of this subsequently developed second malignancy. PTLD
developedin11%ofpatients,ofwhich65%presentedwith
lymphoma. Skin malignancies usually have good
prognosis, PTLD has variable prognosis and GIT
malignancies have poor prognosis[6].
Post transplant malignancies are a problem for
recipients of all types of organ transplants. The risk of
PTLD being more after small bowel, heart and lung
transplant than renal and liver transplants [10]. Reported
incidence of cancer in renal transplant recipients is 2.3-
169 Apollo Medicine, Vol. 7, No. 3, September 2010
POST TRANSPLANT MALIGNANCY – ABRIEF REVIEW
Veena Malhotra, Sumaid Kaul and Deep Shikha Arora
Senior Consultants, Department of Histopathology, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi 110 076, India.
Correspondence to: Dr Veena Malhotra, Senior Consultant, Department of Pathology, Indraprastha Apollo Hospitals,
Sarita Vihar, New Delhi 110 076, India
E-mail: veena_m@appollohospitals.com
Immunosuppressed allograft recipients have three to five folds increase in cancer risk as compared to age
matched general population. The most common malignancies encountered are Non Melanotic Skin Cancer,
Post Transplant Lymphoproliferative Disorder and Kaposi’s Sarcoma. Duration of immunosuppressive
therapy and/or type of immunosuppressive agents are important controllable factors which have an impact in
the development of tumors. Oncogenic viruses have an important role in the development of these
malignancies.
Key words: Post transplant malignancy, Immunosuppressive agents.

3. Apollo Medicine, Vol. 7, No. 3, September 2010 170
Review Article
31 % in published series [11]. Data from registry of
International Heart and Lung Transplantation (ISHLT)
shows that amongst the heart transplant recipients, 3.1% of
survivingpatientsdevelopsomeformofmalignancyafter1
year, which increased to 16.1% in 5 years survivors and
26.2% in 8 years survivors. Data from lung transplant
recipients showed the same trend [12]. USRDS data
showed that in renal transplant recipients cumulative
incidence of cancer excluding NMSC is 3.3% at 1 year and
7.5% at 3 years [13].
Pathogenesis
All human beings are continuously being exposed to
carcinogensormutagens.Thesemutationsaredealtwithby
immune surveillance mechanism. Immunosuppressive
therapy resulting in lack of adequate immune surveillance
plays a key role in development of post transplant
malignancies. This is coupled with conventional
predisposing factors for development of tumors. Common
riskfactorsareincreasingageofpatient,cigarettesmoking,
exposure to ultraviolet light, total sun burden, latent
oncogenic viruses, previous exposure to carcinogens and
analgesic abuse [14]. Geographical factors such as
predispositiontocertainmalignanciesinsomecountriesi.e.
liver tumors in South East Asia and GI malignancies in
Japan, also play a role. Genetic predisposition for certain
malignancies also contributes [15]. The duration of
immunosuppressive therapy, and/or type of
immunosuppressive agents are the important controllable
factors which have an impact on the development of PTM.
In development of post transplant malignancies
potentially oncogenic viruses play a major role. Human
Herpes Virus-8 (HHV8) is associated with Kaposi’s
sarcoma,HumanPapillomaVirus(HPV)8and19withskin
cancer, HPV58 with Bowen disease, Epstein Barr Virus
(EBV) with PTLD, Hepatitis B and C virus with
hepatocelullar carcinoma [16] . PTLD in particular is
related to EBV with 98% of cases related with latent EBV
infection [17].
It has been suggested that duration and type of
immunosuppressive agent used can affect cancer risk.
Number of studies demonstrate that incidence of PTM
increase after the introduction of the calcineurin inhibitor
(cyclosporin), whereas a few studies report no increase in
the risk of cancer [17-19]. An induction regimen that
contains lymphocyte depleting antibodies such as OKT3
andantithymocyteglobulinisawelldocumentedriskfactor
for the development of PTLD [16]. Cyclosporin may cause
cancerprogressionthroughdirectcellulareffectandalsoby
increased expression of transforming growth factor B
(TGF-B) [20]. In addition, a role for cyclosporin in
stimulatingangiogenesismediatedbyVascularEndothelial
GrowthFactor(VEGF)hasalsobeendemonstrated[20].In
vitro studies have suggested that cyclosporin induces
malignancy by reduction in p53 induced apoptosis and
suppression of UV induced DNA repair [16]. Purine
analogues such as azathioprin, have also been used in post
transplant patients. Post transplant patients treated with
Purine analogues have a much more rapid development of
skin cancer in comparison those treated with cyclosporine
[16,21].
Potential role of newer immunosuppressive agents that
is proliferation signal inhibitors (PSIs), Siromulus and
Everolimus, in prevention of PTM is increasingly being
evaluated. These new immunosuppressive agents have a
role in prevention, modification and even treatment of post
transplant malignancies [14]. In addition to
immunosuppression, they have antiproliferative effect by
their action on cell cycle. In vitro and vivo studies have
demonstrated that PSI’s can prevent growth of transformed
cells, increase rate of apoptosis in tumor cells, decrease
angiogenesis and thus tumor progression [22-24].
Post Transplant Lymphoproliferative Disorder
(PTLD)
PTLD is that most common malignancy after skin
cancer in solid organ recipients [25]. It is more common in
pediatric patients [26]. WHO has classified PTLD as; (i)
Early lesion characterized by reactive plasmacytic
hyperplasia or infectious mononucleosis type picture; (ii)
PolymorphicPTLDshowingfullrangeofBcellmaturation
from immunoblast to plasma cell, small to medium
lymphocytes and cells resembling centrocytes and (iii)
Monomorphic PTLD which includes B cell neoplasms like
diffuselargeBcelllymphoma,Burkitt’slymphoma,plasma
cell myeloma, T cell lymphoma and Hodgkin’s lymphoma
[27].
The relationship of PTLD with Epstein Barr Virus
(EBV) is well recognized. Immunosuppressive drugs used
in post transplant period can lead to decrease in EBV
specific T cell surveillance and proliferation. Recipients
who are EBV negative and receive graft form EBV positive
individuals are at highest risk for developing PLTD.
Early lesions are most often seen in children and young
adults and usually occur within the first year post
transplantation, while second and third group i.e.
polymorphic and monomorphic PTLD are seen later post
transplantation [10]. In one study, relative risk of
lymphomia in the first 6 months after transplant was 13.8
which decreased to 3.46 between 2.5 to 3 years[17].
Incidence of PTLD is between 5-20 % after heart, lung and
smallboweltransplant.However,theincidenceafterkidney

4. Review Article
171 Apollo Medicine, Vol. 7, No. 3, September 2010
transplant recipient is much lower i.e.1-3% as kidney
transplant recipients require relatively less severe
immunosuppressive treatment [16].
Vast majority of PTLD are host derived. However some
cases can be derived from donor lymphocytes transplanted
within the graft [28]. Sites of predilection for PTLD are
extranodal. Trasplanted organ and digestive tract are most
frequentsites[29].CNSisfrequentlyinvolvedinupto30%
cases [30]. PTLD arising within one year of transplant is
usually associated with EBV infection and commonly
involves graft. This may suggest permissive role of graft
microenviorment in the pathogenesis [31].
Most of the PTLD are B cell type,Tcell lymphomas are
only about 15% of these. T cell lymphomas tend to occur
late and affect extranodal sites. HTLV-1 virus has been
implicated in pathogenesis of Tcell lymphoma. [32].
Duration, degree and type of immunosuppressive agent
used greatly influence development of PTLD. Introduction
of triple therapy i.e. cyclosporin, OKT3 antibody and
antithymocyte globulin is associated with increased risk
[33]. There is higher risk of PTLD with tacrolimus than
cyclosporin therapy in kidney transplant recipient [34].
Effortshavebeenmadetoidentifypatientathighriskof
developing PTLD by monitoring EBV-DNA load. No
threshholdvalues predictiveofdevelopmentofPTLDhave
been identified [35]. However, a rising trend of EBV- DNA
in a particular patient may define patient at risk [36]. Serial
raised IL-10 levels and a unique monoclonal serum protein
has been identified in patients who developed
PTLD [37,38]. Vaccine against EBV may provide
protection to post transplant patients [39].
Reduction in immunosuppression is first line of
treatment in the management of patients with PTLD.
Complete regression of early lesions and polymorphic
PTLD usually occurs as a result. No standard guidelines
exist, but decreasing cyclosporin/tacrolimus by 50% and
discontinuing azathioprin or mycophenolate is
recommended[40].Immunosuppressionshouldbereduced
to minimal possible safe level keeping in mind graft
survival. Twenty five to 50% patients respond to reduction
in immunosuppression alone. Beneficial effect of antiviral
agents such as cyclovir is doubtful [25].
For last few years monoclonal antibody therapy
(rituximab) directed against B cell receptor (CD20) has
beenintroducedintreatmentofBcellPTLDwithpromising
results [41-44]. Whether demonstration of CD20
expression in biopsy is prerequisite for starting treatment is
not well established. When to start rituximab therapy is
another issue. Whether the treatment should be initiated
after absence of response to reduction in
immunosuppression treatment or simultaneously is still
debated [29].
It is suggested that in monomorphic PTLD, starting
rituximabatthesametimeasreducingimmunosuppression
is a justified approach, which increases the chances of
complete remission [29]. In cases which are refractive to
first line treatment by rituximab, it is yet unclear whether
extendedtreatment byrituximabis appropriateor whether
polychemotherapy should be initiated. Because of higher
rate of treatment related morbidity and mortality, use of
rituximabhasbecomemorecommon[45].Caseserieshave
described response rate with single agent rituximab of
around 60% [45]. Finally, adoptive T-cell immunotherapy,
via infusion of EBV- specific CTLs in patients with EBV-
positive PTLD has shown promise [45].
PSIs have shown promising results in the treatment of
PTLD [46]. Data from centers in Europe of nineteen post
renal transplant patients with PTLD have been pooled. In
these patients calcineurin inhibitor was withdrawn in
eighteen and minimized in one with simultaneous
conversion to PSIs. Concomitant CHOP was given in six
andrituximabinanothersix.Fifteenoutofeighteenpatients
showedremissionwhichwasmaintainedfor6to56months
[46]. Radiation therapy is method of treatment for CNS
lymphoproliferative disease [30].
Kaposi’s Sarcoma (KS)
The incidence of Kaposi’s Sarcoma (KS) in transplant
patients may be as high as 500 times than in healthy
individuals [7,47]. In renal transplants it is seen in upto 6%
of recipients though recent data demonstrates a lower
overall incidence of 8.8 cases of KS per 1,00,000 person
years[5].PrevalenceofKSintransplantrecipientsdepends
on geographical location, ranging from 0.5% in western
countries such as USAto 5.3% in SaudiArabia. Majority of
cases occur in patient from Mediterranean, Jewish,Arabic,
CaribbeanorAfricanethnicgroups[7,47].Themediantime
from transplantation to diagnosis of KS is about 1.5 years
[48]. KS presents as cutaneous involvement in about 80%
cases. Visceral involvement is seen in 20% cases. Lungs,
GIT and lymphoid tissue can be involved [47, 49]. The
pathogenesis of KS is related to the use of immuno-
suppressive drugs and subsequent viral infection [45].
HHV-8 is implicated in the pathogenesis of tumor
development.
The first association of KS and HHV-8 was made when
virus was isolated from KS tissue in AIDS patients [50].
Various mechanisms may be involved in HHV-8 induced
tumor development. HHV-8 proinflammatory proteins
might directly inhibit apoptosis and there by promote cell

5. Apollo Medicine, Vol. 7, No. 3, September 2010 172
Review Article
transformation [51]. The virus might also modulate the
major histocompatibity class 1 antigen presentation
pathway making infected host cells invisible to cytotoxic T
lymphocyte surveillance [51]. Development of KS may
involve initial latent HHV-8 infection of endothelial cells
andsubsequentconversioninspindlecells.Thisisfollowed
byproliferativephaseandexpressionofalyticprotein,viral
G protein coupled receptor (vGPCD). In endothelial cells
vGPCR oncoprotein increases secretion of VEGF and
plays a pivotal role in development of tumor [52 ].
Immunosuppresion is the key contributing factor for
development of tumors. Use of cyclosporin as an
immunosuppressive drug in post transplant patients is
associated with a higher incidence of Kaposi’s sarcoma.
[47]. Reduction or discontinuation of immunosuppresssion
is the first line treatment for KS.
Conversion of cyclosporin to low therapeutic doses of
mycophenolate mofetil can lead to regression of KS [53].
PSIs (sirolimus and everolimus) through specific effect on
VGEF may provide advantage of both immunosuppressive
and antineoplastic activity [54]. PSIs impair VEGF
production and limit response of endothelial cells to VEGF
in animal models [54, 55]. Recurrence after reduction or
change in immunosuppresion has been treated by
chemotherapy, Anthracycline based chemotherapy is the
usual line of treatment [45]. Paclitaxel has also shown
success in two phase II trials [56]. Imatinib (C-kit inhibitor)
and antiangiogenic agents like bevacizumab may also have
a role in treating KS [56-58].
NON MELANOTIC SKIN CANCER
Non melanotic skin cancer (NMSC) affects large
number of organ transplant patients. Basal cell carcinoma
(BCC) and squamous cell carcinoma (SCC) account for
more than 90% of NMSC in transplant recipients [7].
Squamous cell carcinoma is the most common form of skin
cancer in these patients occurring at an incidence 65- 250
times greater than general population while incidence of
BCC is increased 10 fold after transplant [7].This indicates
that normal ratio of 4:1 of BCC to SCC is reversed in
transplant recipients [7,59].
Overall cumulative incidence of NMSC after
transplantationrangesfrom2-24%after5yearsand7-33%
after10years[60].Lifelongimmunosuppressionisthemost
important factor in the pathogenesis of NMSC. In addition,
UVexposure,HPVinfection,andgeneticfactorsalsoplaya
role. Mutations of p53 and proto-oncogenes may occur [7].
Fair skinned people living in countries with hot climate
andhighultravioletexposurearemoreatriskofdeveloping
post transplant NMSC [61]. Ultraviolet radiations, in
addition to its role as mutagen, have immunosuppressive
properties in the skin [7, 60]. Older age, male sex, presence
of permalignant lesions such as actinic keratosis and
cigarette smoking has also been associated with SCC and
BCC [60].
Transplant recipients should be warned about sun
exposure. Studies have demonstrated beneficial effect of
systemicretinoidchemoprophylaxisintransplantrecipients
[45,62].However,areboundeffectwithhigherincidenceof
NMSC after discontinuation of therapy is also reported.
Standard therapy for NMSC includes Mohs’micrographic
surgery, superficial ablative therapy, cytotherapy and
photodynamic therapy along with attenuation of
immunosuppresion [63].
Consensus guidelines for immunosuppression
reduction have been developed [64]. Extent of
immunosuppressionandtypeofimmunosuppressiveagents
used may play a critical role. A recent study indicated that
incidenceNMSCincreasedfrom19%atlessthan5yearsto
47% after more than 20 years of immunosuppressive
therapy [65]. A study in liver transplant receipient showed
mycophenolate mofetil (MMF) was associated with
increased risk of NMSC although this risk didn’t remain
after multivariate anlaysis [66], PSIS like sirolimus have
potential for reducing the incidence of NMSC [67].
Compared with 5% incidence of NMSC in cyclosporin
treated patients, no malignancies were observed in patients
receiving sirolimus as base therapy [68]. Thus cyclosporin
free sirolimus based immunotherapy may reduce incidence
of post transplant skin malignancy.
CONCLUSION
• Allograft organ recipients have three to five folds
increase in cancer risk as compared to age matched
general population.
• Post transplant immunosuppressive therapy resulting
in impaired cancer surveillance and facilitating the
action of oncogenic substances including oncogenic
viruses are key factors in pathogenesis.
• The most common malignancies encountered in post
transplant recipients are NMSC (upto 82%), PTLD
(upto 11%) and KS (upto 6%).
• PTLD has been classified by WHO as (i) early lesion
characterized by infectious mononucleosis type
picture or plasma cell proliferation, (ii) polymorphic
PTLD and; (iii) monomorphic PTLD. EBV has
important role in causing PTLD.
• Prevention of post transplant malignancies by
judicious use of immunosuppressive agents and early

6. Review Article
173 Apollo Medicine, Vol. 7, No. 3, September 2010
detection is important.
• Early lesions of PTLD regress by withdrawing
immunosuppressive agents.
• Newer agents like PSIs have been shown to have
simultaneous immunosuppressive and antitumor
properties and may play a promising role in
management of post transplant patients.
REFERENCES
1. ANZDATA Australia and New Zealand Dialysis and
Transplant Registry 2006.Available www.anzdata.org.au.
Accessed January 2007.
2. Briggs JD. Causes of death after renal transplantation.
Nephrol Dial Transplant 2001, 16: 1545-1549.
3. Trofe J,Beebe TM, Buell JF, et al. Post transplant
malignancy. Prog Transplant 2004; 14 (3): 193-200.
4. Dantal J, Pohanka E. Malignancies in renal
transplantation: an unmet medical need. Nephrol Dial
Transplant 2007; 22 (supp 1): i4-i10.
5. Stallone G, Schena A, Infante B, et al. Sirolimus for
Kaposi’s sarcoma in renal transplant recipients. N Eng J
Med 2005; 352: 1317- 1323.
6. Winkelhorst JT, Brokelman WJ, Tiggeler RG, et al.
Incidence and clinical course of denovo malignancies in
renal allograft recipients. Eur J Surg Oncol 2001; 27: 409-
413.
7. Euvrard S, Kantitakis J, ClaudyA. Skin cancers after organ
transplantation. N Eng J Med 2003; 348: 1681-1691.
8. Penn I. Post transplant malignancy: The role of
immunosuppression. Drug Safety 2000; 23 (2): 101-113.
9. Kasiske BL, Snyder JJ, Gilbertson DT, et al. Cancer after
kidney transplantation in the United States. Am J
Transplant 2004; 4: 905-913.
10. Taylor Al, Marcus R, Bradly JA. Post transplant
lymphoproliferative disorders (PTLD) after solid organ
transplantation. Crit Rev Oncol Hematol 2005; 56: 155-
167.
11. Andrews A. Cancer incidence after immunosuppressive
treatment following kidney transplantation. Crit Rev Oncol
Hematol 2005; 56: 71-85.
12. Taylor DO, Edwards LB, Boucek MM, et al. Registry of
International Society for Heart and Lung Transplantation.
Twenty second official adult heart transplant report 2005; J
Heart Lung Transplant 2005; 24: 945-955.
13. USRDS website available at http: www.usrds.org
Accessed Jan 2007.
14. Chapman JR, Campistol JM. Malignancy in renal
transplantation; opportunities with proliferation signal
inhibitors. Nephrol Dial Transplant 2007; 22 (suppl.1): i1-
i3.
15. Morath C, Mueller M, Goldschmidt H, et al. Malignancy in
renal transplantation. J Am Soc Nephrol 2004; 15: 1582-
1588.
16. Gutierrez Dalmau A, Campistol JM. Immunosuppressive
therapy and malignancy in organ transplant recipients. A
systematic review Drugs 2007; 67 (8): 1167-1198.
17. Opelz G, Dohler B. Lymphomas after solid organ
transplantation : a collaborative transplant study report.
Am J Transplant 2004; 4: 222-230.
18. Vogt P, Frei U, Repp H, et al. Malignant tumors in renal
transplant recipients receiving cyclosporine: survey of 598
first kidney transplantations. Nephrol Dial Transplant
1990; 5: 282-288.
19. Birkeland SA, Hamilton DutoitS. Is post transplant
lymphoproliferative disorders (PTLD) caused by any
specific immunosuppression drug or by the
transplantation per se? Transplantation 2003; 76: 984-
988.
20. Hojo M, Morimoto T, Maluccio, et al. Cyclosporine induced
cancer progression by a cell autonomous mechanism.
Nature 1999; 397: 530-534.
21. O’Donovan P, Perrett CM, Zhang X,et al. Azathioprine and
UVA light generatesmutagenic oxidative DNA damage.
Science 2005: 309: 1871-1874.
22. Guba M, von breitenbuch P, Steinbauer M, et al.
Rapamycin inhibits primary and metastatic tumor growth
by antiangiogenesis; involvement of vascular endothelial
growth factor. Nat Med 2002; 8: 128-135.
23. Koehl GE, Sclitt HJ, Geissler EK. Raparmycin and tumor
growth: mechanisms, behind its anticancer activity.
Transplant Rev 2005; 19: 20-31.
24. Majewski M, Korecka M. Joergensen J, et al.
Immunosuppressive TOR kinase inhibitor everolimus
(RAD) suppresses growth of cells derived from post
transplant lymphoproliferative disorder at allograft
protecting doses. Transplantation 2003; 75: 710-717.
25. La Casce AS. Post transplant lymphoproliferative
disorders. The Oncologist 2006; 11: 674-680.
26. McDonald RA, Smith JM, Ho M, et al. Incidence of PTLD in
pediatric renal transplant recipients receiving basiliximab,
calcineurin inhibitors, sirolimus and steroids. Am J
Transplant 2008 ; 8: 984-989.
27. Harris NL, Ferry JA, Swerdlow SH. Post transplant
lymphoproliferative disorders; Summary of society for
hematolopathology workshop. Semin Diagn Pathol 1997;
14: 8-14.
28. Weissmann DJ, Ferry JA. Harries NL, et al. Post
transplantation lymphoproliferative disorders in solid
organ recipients are predominantly aggressive tumors of
host origin.Am J Clin Pathol 1995 ; 103 : 748-755.
29. Bakker NA, van Imhoff GW. Post transplant
lymphoproliferative disorders: form treatment to early
detection and prevention. Haematologica 2007; 92: 1447-
1450.
30. Penn I, Porat G. Central nervous system lymphomas in

7. Apollo Medicine, Vol. 7, No. 3, September 2010 174
Review Article
organ transplant recipients. Transplantation 1995; 59:
240-244.
31. Bakker NA, Van Imhoff GW, Verschuuren EA, et al. Early
onset post -transplant lymphoproliferative disease is
associated with allograft localization. ClinTransplant 2005;
19: 327-334.
32. Rajakarlar R, Bhattacharya N, Norton A, et al. Post
transplant T- Cell lymphoma:Acase series of four patients
from a single unit a review of literature. Am J Transplant
2004; 4: 1534-1538.
33. Libertiny G, Watson CJ, Gray DW, et al. Rising incidence of
post transplant lymphoproliferative disease in kidney
transplant recipients. Br J Surg 2001; 88: 1330-1334.
34. Caillard S, Dharnidharka V,Agodoa L, et al.Post transplant
lymphoproliferative disorder after renal transplantation in
the United States in era of modern immunosuppression.
Transplantation 2005; 80: 1233-1234.
35. Bakker NA. Von Imhoff GW, Verschuuren EA, et al.
Presentation and early detection of post transplant
lymphoproliferative disorder after solid organ
transplantation. Transplant Int 2007; 20: 207-218.
36. Bakker NA, Verschuuren EA, Erasmua ME, et al. Epstein-
Barr virus DNA load monitoring late after lung
transplantation : a surrogate marker of the degree of
immunosuppression and a safe guide to reduce
immunosuppression. Transplantation 2007; 83: 433-438.
37. Baiocchi OC, Colleoni GW, Caballero OL, et al. Epstein-
Barr viral load, interleukin-6 and interleukin-10 levels in
post transplant lymphoproliferative disease : a nested
case-control study in a renal transplant cohort. Leuk
Lymphoma 2005; 46: 533-539.
38. Tsai DE, Aqui NA, Tomaszewski JE, et al. Serum protein
electrophoresis abnormalities in adult solild organ
transplant patents with post transplant lymphoproliferative
disorders Clin Transplant 2005; 19: 644-652.
39. Gu Sy, Huang TM, Ruan L, et al. First EBV vascine trial in
humans using recombinant vaccinia virus expressing the
major membrane antigen. Dev Biol Stand 1995; 84: 171-
177.
40. Paya CV, Fung JJ, Nalesnik MA, et al. Epstein Barr virus
induced post transplant lymphoproliferative disorders.
ASTS / ASTP EBV-PTLD task force and the Mayo chronic
organised International Consensus Development
Meeting. Transplantation 1999; 68: 1517-1525.
41. Elstrom RL, Andreadis C, Aqui NA, et al. Treatment of
PTLD with rituximab or chemotherapy. Am J Transplant
2006; 6: 569-576.
42. Benkerrou M, Jais JP, Leblond V, et al. Anti B-cell
monoclonal antibody treatment of severe post transplant B
lympholiferative disorder ; prognostic factors and long term
outcome. Blood 1998; 92 : 3137-3147.
43. Choquet S, Leblond V, Herbrecht R, et al. Efficacy and
safety of rituximab in B cell post transplantation
lymphoproliferative disorders. Result of prospective
multicenter phase 2 study Blood 2006; 107: 3053-3057.
44. Gonzalez- Barca E, Domingo –Domenech E, Capote FJ,
et al.The GEL/TAMO, GELCAB, and GOTEL, Prospective
phase II trial of extended treatment with rituximab in
patients with B cell post lymphoproliferative disease.
Haematologica 2007; 92: 1490-1495.
45. Zafar SY, Howell DN, Gockerman JP. Malignancy after
solid organ transplantation: An overview. The Oncologist
2008; 13 (7): 769-778.
46. Pascual J. Post transplant lymphoproliferative disorder the
potential of proliferation signel inhibitors Nephrol Dial
Transplant 2007; 22(supp 1): i 27-i 35.
47. Mendez JC, Paya CV. Kaposi’s sarcoma and
transplantation. Herpes 2000; 7: 18-23.
48. Mbulaiteye SM, Engels EA. Kaposi’s Sarcoma risk among
transplant recipients in the United States (1993-2003). Int J
Cancer 2006; 119: 2685-2691.
49. Tan HH, Gob CL. Viral infection effecting the skin in organ
transplant recipients, epidemiology and current
management strategies An, J Clin Dermatol 2006; 7: 13-
29.
50. Chang Y, Cesarman E, Pessin MS, et al. identification of
herpes virus like DNA sequences in AIDS associated
Kaposi’s Sarcoma. Science 1994; 266: 1865-1869.
51. Rezaee SA, Cunninghan C, Daison AJ, et al. Kaposi’s
sarcoma associated herpes virus immune modulation ;An
overview J, Gen Virol 2006; 87: 1781-1804.
52. Campistol JM, Gutierrez Dalmau A, Torregrosa JV.
Conversion to sirolimus ; a successful treatment for post
transplantation Kaposis Sarcoma. Transplantation 2004 ;
77: 760-762.
53. Hussein MM, Mooij JM, Roujoulen HM. Regression of post
transplant Kaposi’s sarcoma after discontinuing
cyclosporin and giving mycophenolate mofetil instead,
Nephrol Dial Transplant 2000; 15: 1103-1104.
54. Campistol JM, Schena FP. Kaposi’s sarcoma in renal
transplant recepients - the impact of proliferation signet
inhibitor Nephrol Dial Transplant 2007; 22 (supp 1): i17-
i22.
55. Guba M, von Breitenbuch P, Steinbauer M, et al.
Rapamycin inhibits primary and metastatic tumor growth
by antiangiogenesis ; involvement of vascular endothelial
growth factor. Nat Med 2002; 8: 128-135.
56. Gill PS, Tulpule A, Espina BM, et al. Paclitaxel is safe and
effective in treatment of advanced AIDS related Kaposi’s
Sarcoma. J Clin Oncol 1999; 17: 1876-1883.
57. Volkan P, Zinser JW, Correa Rotter R. Molecularly targeted
therapy for Kaposi’s Sarcoma in kidney transplant patient:
case report, “ what worked and what did not” BMC Nephrol
2007; 8: 6.
58. Koon HB, Bubley GJ, Pantanowitz L, et al. Imatinib –
induced neoplasm of AIDS related Kaposi’s Sarcoma. J
Clin Oncol 2005; 23: 982-989.
59. Ramsay HM, FryerAA, Reece S, et al. Clinical risk factors
associated with nonmelanoma skin cancer in renal

8. Review Article
175 Apollo Medicine, Vol. 7, No. 3, September 2010
transplant recipients.Am J kidney Dis 2000; 36: 167-176.
60. Urich C, Schmook T, Sachse MM, et al. Comparative
epidemiology and pathogenic fectors for non melanoma
skin cancer in organ transplant patients. Dermatol Surg
2004; 30: 622-627.
61. de Fijter JW. Use of proliferation signel inhibitors in non
melanoma skin cancer following renal transplantation.
Nephrol Dial Transplant 2007; 22 (supp 1): i23-i26.
62. Kovach BT, Sams HH, Stasko T. Systemic strategies for
chemoprevention of skin cancer in transplant recipients.
Clin Transplant 2005; 19: 726-734.
63. Berg D, Ofley CC. Skin cancer in organ transplant
recipients: epidermiology, pathogenesis and manage-
ment. JAmAcad Dermatol 2002; 47: 1-17.
64. Otley CC, Berg D, Ulrich C, et al. Reduction of
immunosuppression for transplant associated skin
cancer; Expert consensus survey. Br J Dermatol 2006;
154: 395-400.
65. Caroll RP, Ramsay HM, Frayer AA, et al. Incidence and
prediction of non melanoma skin cancer post renal
transplantation; a prospective study in Queensland,
Austrialia.Am J kidney Dis 2003; 41: 676-683.
66. Herrero JI, EspanaA, Quiroga J, et al. Nonmelanoma skin
cancer after liver transplantation. Study of risk fectors.
Liver Transpl 2005; 11: 1100-1106.
67. Campistol JM, Eris J, Oberbauer R, et al.Sirolimus therapy
after early cyclosporine withdrawl reduces the risk for
cancer in adult renal transplantation. J Am Soc Nephrol
2006; 17: 581-589.
68. Mathew T, Kreis H, Friend P. Two year incidence of
malignancy in sirolimus treated renal transplant recipients;
results from five multicenter studies. Clin Transplant 2004;
18: 446-449.

9. Apollo hospitals: http://www.apollohospitals.com/
Twitter: https://twitter.com/HospitalsApollo
Youtube: http://www.youtube.com/apollohospitalsindia
Facebook: http://www.facebook.com/TheApolloHospitals
Slideshare: http://www.slideshare.net/Apollo_Hospitals
Linkedin: http://www.linkedin.com/company/apollo-hospitals
Blog: http://www.letstalkhealth.in/