post - transplant lymphoproliferative disorder ( ptld ) is a recognized complication exclusive to solid organ transplant recipients and is the second most common malignancy after skin cancers in these patients ( ondrus et al . , 1999 ) .
malignancy is the leading cause of death after infections and cardiovascular disease in renal transplant recipients .
the incidence of ptld is about 1 % in adult renal transplant recipients but has been reported to be higher in paediatric recipients ( dharnidharka et al . , 2001 ) .
the incidence is lowest in renal transplant recipients compared to heart , liver or lung transplant recipients and can be as high as 6 - 10 % in lung transplants recipients ( mihalov et al . , 1996 ) .
the intensity and type of immunosuppression are associated with the development of ptld ( dharnidharka et al . , 2001 ) .
other risk factors include epstein - barr virus ( ebv ) seronegative recipients ( cockfield et al . , 1993 ;
1994 ) , co - existing cytomegalovirus ( cmv ) infection ( manez et al.,1994 ; walker et al .
1995 ) , the use of monoclonal anti - cd3 antibody and cadaveric transplant recipients . despite treatment
, ptld carries 60 % mortality ( caillard , et al . , 2006 ) .
initial therapy in ptld is immunosuppression reduction which can sometimes result in complete remission but carries the risk of rejection ( tsai et al . , 2001 ) .
we noted an increase in the incidence of ptld at our institution ( ciancio et al . , 1997 ) .
this prompted the review of patient characteristics , immunosuppression regimen and risk factors for the development of ptld and its outcomes in our transplant cohort .
we retrospectively reviewed records of all renal transplant recipients under follow up at our institution over the last 7 years ( 2005 - 2011 ) from our database and collected data on the patients diagnosed with ptld after renal transplantation .
we collected the demographics of patients ( age , gender and sex ) , type of renal transplant , the use and type of an induction agent , immunosuppressive regimen , renal function and age at diagnosis of ptld .
we also collected data on primary diagnosis of esrd , time to developing ptld , type of donor kidney , donor and recipient cmv and ebv serology , episodes of rejection , episode of calcineurin inhibitor toxicity , treatment received and outcome .  
the diagnosis of ptld was made based on histology and in most cases from a renal transplant biopsy specimen .
the specimens were all reviewed by a consultant histopathologist who verified the diagnosis of ptld .
ptld was incidentally diagnosed on a transplant biopsy that was performed for an unexplained rise in serum creatinine in three patients .
the fourth patient presented with symptoms of fever , upper respiratory tract infection and left submandibular lymphadenopathy and ptld was diagnosed from lymph node biopsy .
once ptld was diagnosed , patients were fully investigated and 2 patients had systemic involvement . in most of the patients we did not have the donor details in terms of cmv and ebv serology , and type of induction agent ( if used ) as majority were done overseas with commercial donors .
ptld occurred in 6 % of our transplant patients and was notably higher in our cohort than the 1 % reported rate ( gerstenkorn et al . , 2001 ) .
three cases of ptld were incidentally diagnosed on an allograft biopsy for an acute rise in serum creatinine .
ptld can occur within the allograft and should be considered as a differential diagnosis for acute rejection .
the incidence of ptld varies with the organ transplanted , the presence and intensity of immunosuppression ( especially cyclosporine a based regimens ) , ebv seronegative recipients , co - existing cmv infection and cadaveric transplant recipients ( cockfield et al .
, 1993 ; manez et al . , 1994 ; walker et al . , 1995 ; izadi et al . , 2011 ;
2012 ) the use of muromonab - cd3 ( okt3 ) as an induction agent has also been associated with the development of ptld ( cockfield et al . , 1993 ; walker et al . , 1995
we believe the possible reasons for our higher incidence of ptld are ebv infection and a higher degree of immunosuppression . until recently ,
a third of all malaysian renal transplants were commercial cadavers and therefore no data is available on the ebv status of the donor . in case 3 , the patient had two previous episodes of rejection , hence the need for augmented immunosuppression .
several studies have shown a higher incidence of ptld in paediatric renal transplant recipients as many paediatric patients are ebv naive compared to the adult population who is predominantly ebv seropositive ( dharnidharka et al . , 2001 ) .
studies have demonstrated ebv seronegative pre - transplantation increases the risk of primary infection with ebv and development of ptld increases by 76 six fold ( walker et al . , 1995 ; sampaio et al . ,
ptld can be classified into a polyclonal or monoclonal proliferation of b lymphocytes or t lymphocytes ( swerdlow 1992 ; anonymous , 2004 ) .
most ptlds arise from b cell as ebv has a predilection for b cells .  
the majority of our patients presented within 18 months of transplantation which is in keeping with reported data .
the risk of developing ptld is highest in the first year after solid organ transplantation when immunosuppression is at its highest and is mostly driven by ebv infection .
studies have shown that recipients with late onset ptld frequently presented with monomorphic lesions and a significantly higher risk of disseminated disease ( izadi et al . , 2011 ) .
our study found similar findings in that our first two cases presented early on with polymorphic ptld .
allograft involvement can occur in renal transplant recipients with ptld as evidenced by 3 of our cases with it being localized to the graft only .
khedmat and taheri ( 2010 ) demonstrated 37 % of their patients had ptld confined to allograft and this subset of patients had better survival than other ptld patients unless they developed multi - organ involvement .
five - year survival rate was 73 % for graft ptld and 42 % for other localizations .
graft ptld patients had shorter time from transplant to ptld and were more likely to present as polyclonal and polymorphic ( khedmat and taheri , 2010 ) .
treatment of ptld involves a few regimens - the mainstay of treatment is reduction of immunosuppression in all cases although currently , there is no standardized approach ( tsai et al . , 2001 ) .
european guidelines recommend stopping the antimetabolite and minimizing the calcineurin inhibitor by at least 50 % , some say about 20 % every two weeks until about 30 % of the initial dose ( european best practice guidelines , 2002 ) .
however , immunosuppression reduction is associated with a higher risk of graft rejection and graft loss with reported rejection rates of 37 % ( tsai et al . , 2001 ) .
reduction of immunosuppression allows the recovery of the recipients t cells which perform surveillance against ebv infected cells .
however , response rate to immunosuppression reduction alone is low ( gerstenkorn et al . , 2001 ) .
estimation of ebv viral load allows pre - emptive prophylaxis by treatment with antiviral agent for at least one month and depending on viral load ( european best practice guidelines , 2002 ) .
however , these agents will only inhibit the lytic phase and decrease the degree of shedding of virus but the number of ebv infected cells is not altered by acyclovir treatment .
other treatment strategies include rituximab monotherapy in cd20-positive b - cell ptld ( elstrom et al . , 2006 ) or chop - like chemotherapy ( choquet et al . , 2007
hematotoxicity , leading to infectious complications and treatment - related mortality is the therapeutic limitation of chop
. renal graft function may be decreased at the time of diagnosis but significantly improves following treatment of the lymphoma ( trappe et al . , 2009 ) .
compared with renal transplant controls with stable graft function , ptld patients receiving chemotherapy had a non inferior graft function at follow - up ( trappe et al . , 2009 ) .
this suggests that the negative impact of immunosuppression reduction on graft function can be compensated by the immunosuppressive effect of chop , suppressing both cell - mediated and humoral immunity through its effects on t and b cells ( gholipour - shoiili et al . , 2011 ) .
overall reported response rates are about 40 - 60 % for single agent rituximab and up to 90 % for sequential treatment with four courses of rituximab followed by four cycles of chop ( trappe et al . ,
anti - cd20 monotherapy is therefore the preferred treatment modality in ptld when patients fail to respond to upfront immunosuppression reduction , although they seem to be less effective in high - risk patients . in our cohort ,
patients with systemic involvement received rituximab with good response rates . in the case of patient 3 ( who was also diabetic ) , he had been treated twice for rejection previously and therefore received higher level of immunosuppression . after the diagnosis of ptld , we reduced his immunosuppression and treated him with rituximab .
about 18 months later , he developed another episode of cellular rejection for which he received high dose steroids , but developed recurrent septicaemia episodes and eventually succumbed to it .
studies demonstrate that survival analysis in patients with renal allograft involvement who underwent allograft nephrectomy had a significantly better outcome compared to non nephrectomised patients ( gholipour - shoiili et al . , 2011 ) . in patients with disseminated ptld
, nephrectomy was not useful and some would consider this a drastic measure , as life on dialysis carries a significant psychosocial burden ( gholipour - shoiili et al . ,
mortality has been reported to be over 50 % ( caillard et al . , 2006 ) .
meta - analysis in liver transplant recipients have reported one and five years survival rate for early onset ptld to be 64 % and 54 % respectively ( izadi and taheri , 2011 ) .
ptld can sometimes be incidentally diagnosed on an allograft biopsy that was performed for rejection . therefore renal transplant recipients who develop allograft dysfunction during the early post - transplantation period should be investigated for potential ptld development at their allograft site .
 post - transplant lymphoproliferative disorder ( ptld ) is a recognized complication exclusive to solid organ transplant recipients and carries a high mortality . 
 we retrospectively reviewed records of all renal transplant recipients under follow up at our institution over the last seven years ( 2005 - 2011 ) . 
 we reviewed the patient characteristics , immunosuppression regimen and risk factors for the development of ptld and its outcomes in our transplant cohort . 
 four out of 63 patients were diagnosed with ptld . 
 ptld was incidentally diagnosed on a transplant biopsy that was performed for an unexplained rise in serum creatinine in three patients . 
 the fourth patient presented with left submandibular lymphadenopathy . 
 majority presented within 18 months of renal transplantation . 
 after the diagnosis of ptld on graft biopsy , all patients were fully investigated and two patients had systemic involvement . in the patients with systemic involvement , reduction of immunosuppression and anti b cell therapy with rituximab was used with good success . 
 the patient with submandibular lymphadenopathy received chemotherapy in addition to reduction of immunosuppression . 
 three ptld cases were polyclonal and diagnosed early whereas the fourth case was monoclonal . 
 ptld can sometimes be incidentally diagnosed on an allograft biopsy performed for rejection . 
 the incidence of ptld in our centre is higher than reports from other centres but our outcome is good if recognised and treated early . 
Introduction
Patients and Methods
Results
Discussion
Conclusion