Post transplant lymphoproliferative disorder: Difference between revisions

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==Overview==
==Overview==


'''Post-transplant lymphoproliferative disorder''' (also known as '''PTLD''') is defined as a [[lymphoid]] (immune cells) and/or plasmacytic [[Proliferation|proliferations]] (rapid increase) due to [[therapeutic]] [[immunosuppression]] after [[Organ (anatomy)|organ]] [[transplantation]] especially in the patients who are undergoing solid organ or [[allogeneic]] (donor) [[hematopoietic stem cell transplantation]]. Patients with post-transplant [[Lymphoproliferative disorders|lymphoproliferative disorder]] may develop serious [[complications]] of [[transplantation]] with [[infectious mononucleosis]]-like [[Lesion|lesions]] due to [[Epstein Barr virus|Epstein-Barr virus]] ([[EBV]]) or [[polyclonal]] [[polymorphic]] [[B-cell]] [[hyperplasia]]. In some cases, [[B-cells]] may undergo mutations which will render them malignant, giving rise to a [[lymphoma]]. The [[malignant]] cell clone can become the dominant proliferating cell type, leading to a group of [[B cell]] [[lymphoma]]s occurring in [[Immunosuppression|immunosuppressed]] patients following [[organ transplant]]. Post transplant lymphoproliferative disorder arises from [[germinal center]] or post-germinal center B cells (B-PTLD), which are normally involved the production of [[antibodies]]  and durable [[Memory B cell|memory B cells]]. Post transplant lymphoproliferative disorder was first discovered by Denis Parsons Burkitt, an Irish physician, in 1965. According to World Health Organization ([[World Health Organization|WHO]]) classification system, post transplant lymphoproliferative disorder may be classified into 4 subtypes: early [[hyperplastic]] lesions, [[polymorphic]] lesions, monomorphic lesions, and classic [[Hodgkin's Lymphoma|Hodgkin-type lymphomas]]. Post transplant lymphoproliferative disorder is very rare, and the [[prevalence]] of post transplant lymphoproliferative disorder remains unknown.  Post transplant lymphoproliferative disorder is more commonly observed among young patients. The medical treatment for post transplant lymphoproliferative disorder, includes: [[immunosuppression]], [[Antiviral Therapy|antiviral]] therapy, [[interferon alpha]] therapy, [[CD20]] [[antibody]] therapy, and [[chemotherapy]].
'''Post-transplant lymphoproliferative disorder''' (also known as '''PTLD''') is defined as a [[lymphoid]] (immune cells) and/or plasmacytic [[Proliferation|proliferations]] (rapid increase) due to [[Immunosuppression|therapeutic immunosuppression]] after organ [[transplantation]] especially in the patients who are undergoing solid organ or [[allogeneic]] (donor) [[hematopoietic stem cell transplantation]]. Post transplant lymphoproliferative disorder was first discovered by Denis Parsons Burkitt, an Irish physician, in 1965. According to World Health Organization ([[World Health Organization|WHO]]) classification system, post transplant lymphoproliferative disorder may be classified into 4 subtypes: early [[hyperplastic]] lesions, [[polymorphic]] lesions, monomorphic lesions, and classic [[Hodgkin's Lymphoma|Hodgkin-type lymphomas]]. Patients with post-transplant [[Lymphoproliferative disorders|lymphoproliferative disorder]] may develop serious [[complications]] of [[transplantation]] with [[infectious mononucleosis]]-like [[Lesion|lesions]] due to [[Epstein Barr virus|Epstein-Barr virus]] ([[EBV]]) or [[polyclonal]] [[polymorphic]] [[B-cell]] [[hyperplasia]]. In some cases, [[B-cells]] may undergo mutations which will render them malignant, giving rise to a [[lymphoma]]. The [[malignant]] cell clone can become the dominant proliferating cell type, leading to a group of [[B cell]] [[lymphoma]]s occurring in [[Immunosuppression|immunosuppressed]] patients following [[organ transplant]]. Post transplant lymphoproliferative disorder arises from [[germinal center]] or post-germinal center B cells (B-PTLD), which are normally involved the production of [[antibodies]]  and durable [[Memory B cell|memory B cells]]. Post transplant lymphoproliferative disorder is very rare, and the [[prevalence]] of post transplant lymphoproliferative disorder remains unknown.  Post transplant lymphoproliferative disorder is more commonly observed among young patients. The medical treatment for post transplant lymphoproliferative disorder, includes: [[immunosuppression]], [[Antiviral Therapy|antiviral]] therapy, [[interferon alpha]] therapy, [[CD20]] [[antibody]] therapy, and [[chemotherapy]].


==Historical Perspective==
==Historical Perspective==
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{| class="wikitable"
{| class="wikitable"
|+
|+
|Category
!Category
|Subtype
!Subtype
|-
|-
|Early [[hyperplastic]] [[Lesion|lesions]]
!Early [[hyperplastic]] [[Lesion|lesions]]
|
|
* [[Infectious mononucleosis]]-type acute illness
* [[Infectious mononucleosis]]-type acute illness
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* Plasmacytic [[hyperplasia]]  
* Plasmacytic [[hyperplasia]]  
|-
|-
|[[Polymorphic]] [[lesions]]
![[Polymorphic]] [[lesions]]
|
|
* Evidence of [[malignant]] [[transformation]]
* Evidence of [[malignant]] [[transformation]]
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* Found in [[immunocompetent]] patients
* Found in [[immunocompetent]] patients
|-
|-
|Monomorphic lesions
!Monomorphic lesions
|'''[[B-cell lymphoma|B-cell lymphomas]]'''
|'''[[B-cell lymphoma|B-cell lymphomas]]'''
* [[Diffuse large B-cell lymphoma]]
* [[Diffuse large B-cell lymphoma]]
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* T-[[Natural killer cell|natural killer]] ([[NK-cells|NK]]) [[lymphoma]]  
* T-[[Natural killer cell|natural killer]] ([[NK-cells|NK]]) [[lymphoma]]  
|-
|-
|Other types
!Other types
|
|
* [[Hodgkin’s disease]]
* [[Hodgkin’s disease]]
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* 90 to 95 percent of patients with post transplant lymphoproliferative disorder shows positive [[Serology|serologic]] of infection especially with [[Epstein Barr virus|Epstein-Barr virus]] ([[Epstein Barr virus|EBV]]) infection.<ref name="pmid7598473">{{cite journal |vauthors=Hanto DW |title=Classification of Epstein-Barr virus-associated posttransplant lymphoproliferative diseases: implications for understanding their pathogenesis and developing rational treatment strategies |journal=Annu. Rev. Med. |volume=46 |issue= |pages=381–94 |date=1995 |pmid=7598473 |doi=10.1146/annurev.med.46.1.381 |url=}}</ref>
* 90 to 95 percent of patients with post transplant lymphoproliferative disorder shows positive [[Serology|serologic]] of infection especially with [[Epstein Barr virus|Epstein-Barr virus]] ([[Epstein Barr virus|EBV]]) infection.<ref name="pmid7598473">{{cite journal |vauthors=Hanto DW |title=Classification of Epstein-Barr virus-associated posttransplant lymphoproliferative diseases: implications for understanding their pathogenesis and developing rational treatment strategies |journal=Annu. Rev. Med. |volume=46 |issue= |pages=381–94 |date=1995 |pmid=7598473 |doi=10.1146/annurev.med.46.1.381 |url=}}</ref>
* Membrane proteins associated with [[Epstein Barr virus|EBV]] plays a major role in contribute to [[B cell]] growth and survival.<ref name="pmid7859281">{{cite journal |vauthors=Mosialos G, Birkenbach M, Yalamanchili R, VanArsdale T, Ware C, Kieff E |title=The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family |journal=Cell |volume=80 |issue=3 |pages=389–99 |date=February 1995 |pmid=7859281 |doi= |url=}}</ref><ref name="pmid9037073">{{cite journal |vauthors=Izumi KM, Kaye KM, Kieff ED |title=The Epstein-Barr virus LMP1 amino acid sequence that engages tumor necrosis factor receptor associated factors is critical for primary B lymphocyte growth transformation |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=94 |issue=4 |pages=1447–52 |date=February 1997 |pmid=9037073 |pmc=19811 |doi= |url=}}</ref><ref name="pmid9580648">{{cite journal |vauthors=Liebowitz D |title=Epstein-Barr virus and a cellular signaling pathway in lymphomas from immunosuppressed patients |journal=N. Engl. J. Med. |volume=338 |issue=20 |pages=1413–21 |date=May 1998 |pmid=9580648 |doi=10.1056/NEJM199805143382003 |url=}}</ref><ref name="pmid11905817">{{cite journal |vauthors=Thorley-Lawson DA |title=Epstein-Barr virus: exploiting the immune system |journal=Nat. Rev. Immunol. |volume=1 |issue=1 |pages=75–82 |date=October 2001 |pmid=11905817 |doi=10.1038/35095584 |url=}}</ref><ref name="pmid10196351">{{cite journal |vauthors=Kaiser C, Laux G, Eick D, Jochner N, Bornkamm GW, Kempkes B |title=The proto-oncogene c-myc is a direct target gene of Epstein-Barr virus nuclear antigen 2 |journal=J. Virol. |volume=73 |issue=5 |pages=4481–4 |date=May 1999 |pmid=10196351 |pmc=104340 |doi= |url=}}</ref><ref name="pmid1331789">{{cite journal |vauthors=Randhawa PS, Jaffe R, Demetris AJ, Nalesnik M, Starzl TE, Chen YY, Weiss LM |title=Expression of Epstein-Barr virus-encoded small RNA (by the EBER-1 gene) in liver specimens from transplant recipients with post-transplantation lymphoproliferative disease |journal=N. Engl. J. Med. |volume=327 |issue=24 |pages=1710–4 |date=December 1992 |pmid=1331789 |pmc=2956494 |doi=10.1056/NEJM199212103272403 |url=}}</ref>
* Membrane proteins associated with [[Epstein Barr virus|EBV]] plays a major role in contribute to [[B cell]] growth and survival.<ref name="pmid7859281">{{cite journal |vauthors=Mosialos G, Birkenbach M, Yalamanchili R, VanArsdale T, Ware C, Kieff E |title=The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family |journal=Cell |volume=80 |issue=3 |pages=389–99 |date=February 1995 |pmid=7859281 |doi= |url=}}</ref><ref name="pmid9037073">{{cite journal |vauthors=Izumi KM, Kaye KM, Kieff ED |title=The Epstein-Barr virus LMP1 amino acid sequence that engages tumor necrosis factor receptor associated factors is critical for primary B lymphocyte growth transformation |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=94 |issue=4 |pages=1447–52 |date=February 1997 |pmid=9037073 |pmc=19811 |doi= |url=}}</ref><ref name="pmid9580648">{{cite journal |vauthors=Liebowitz D |title=Epstein-Barr virus and a cellular signaling pathway in lymphomas from immunosuppressed patients |journal=N. Engl. J. Med. |volume=338 |issue=20 |pages=1413–21 |date=May 1998 |pmid=9580648 |doi=10.1056/NEJM199805143382003 |url=}}</ref><ref name="pmid11905817">{{cite journal |vauthors=Thorley-Lawson DA |title=Epstein-Barr virus: exploiting the immune system |journal=Nat. Rev. Immunol. |volume=1 |issue=1 |pages=75–82 |date=October 2001 |pmid=11905817 |doi=10.1038/35095584 |url=}}</ref><ref name="pmid10196351">{{cite journal |vauthors=Kaiser C, Laux G, Eick D, Jochner N, Bornkamm GW, Kempkes B |title=The proto-oncogene c-myc is a direct target gene of Epstein-Barr virus nuclear antigen 2 |journal=J. Virol. |volume=73 |issue=5 |pages=4481–4 |date=May 1999 |pmid=10196351 |pmc=104340 |doi= |url=}}</ref><ref name="pmid1331789">{{cite journal |vauthors=Randhawa PS, Jaffe R, Demetris AJ, Nalesnik M, Starzl TE, Chen YY, Weiss LM |title=Expression of Epstein-Barr virus-encoded small RNA (by the EBER-1 gene) in liver specimens from transplant recipients with post-transplantation lymphoproliferative disease |journal=N. Engl. J. Med. |volume=327 |issue=24 |pages=1710–4 |date=December 1992 |pmid=1331789 |pmc=2956494 |doi=10.1056/NEJM199212103272403 |url=}}</ref>
** LMP-1-Latent membrane protein 1  
** LMP-1-Latent membrane protein 1
** LMP-2A-Latent membrane protein 2
** LMP-2A-Latent membrane protein 2
** [[Epstein Barr virus|EBNA-2]](Epstein-Barr nuclear antigen 2) and  
** [[Epstein Barr virus|EBNA-2]] (Epstein-Barr nuclear antigen 2) and  
** EBNA-LP(Epstein-Barr nuclear antigen 2 ladder protein)
** EBNA-LP (Epstein-Barr nuclear antigen 2 ladder protein)


*  
*  


*Post transplant lymphoproliferative disorder arises from [[germinal center]] or post-[[germinal center]] [[B cell]]<nowiki/>s (B-PTLD) , which are normally involved the production of [[antibodies]] and durable [[Memory B cell|memory B cells]].
*Post transplant lymphoproliferative disorder arises from [[germinal center]] or [[Germinal center|post-germinal center B cell]]<nowiki/>[[Germinal center|s]] (B-PTLD) , which are normally involved the production of [[antibodies]] and durable [[Memory B cell|memory B cells]].
*The [[pathogenesis]] of post transplant lymphoproliferative disorder is also characterized by the production of [[interleukin-10]].
*The [[pathogenesis]] of post transplant lymphoproliferative disorder is also characterized by the production of [[interleukin-10]].


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*On [[gross]] pathology, characteristic findings of post transplant lymphoproliferative disorder, include:
*On [[gross]] pathology, characteristic findings of post transplant lymphoproliferative disorder, include:
**Resemblance to large cell [[Lymphoma|lymphomas]]
**Resemblance to large cell [[Lymphoma|lymphomas]]
**No remarkable findings
**Palpable [[lymphadenopathy]] based on the level of involvement


*On microscopic [[histopathological]] analysis, characteristic findings of post transplant lymphoproliferative disorder, include:
*On microscopic [[histopathological]] analysis, characteristic findings of post transplant lymphoproliferative disorder, include:
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**[[Epstein-Barr virus]]<ref name="pmid15979320">{{cite journal |vauthors=Taylor AL, Marcus R, Bradley JA |title=Post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation |journal=Crit. Rev. Oncol. Hematol. |volume=56 |issue=1 |pages=155–67 |year=2005 |pmid=15979320 |doi=10.1016/j.critrevonc.2005.03.015 |url=}}</ref>
**[[Epstein-Barr virus]]<ref name="pmid15979320">{{cite journal |vauthors=Taylor AL, Marcus R, Bradley JA |title=Post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation |journal=Crit. Rev. Oncol. Hematol. |volume=56 |issue=1 |pages=155–67 |year=2005 |pmid=15979320 |doi=10.1016/j.critrevonc.2005.03.015 |url=}}</ref>
**[[Immunosuppression]]
**[[Immunosuppression]]
**Recipient [[age]]: under 25 years  
**Recipient [[age]]: under 25 years
**[[Ethnicity and health|Ethnicity]]
**[[Ethnicity and health|Ethnicity]]
**History of pretransplant [[malignancy]]
**History of pretransplant [[malignancy]]
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==Differentiating Post Transplant Lymphoproliferative Disorder from Other Diseases==
==Differentiating Post Transplant Lymphoproliferative Disorder from Other Diseases==
*Post transplant lymphoproliferative disorder must be differentiated from other diseases that cause [[fatigue]], [[weight-loss]], and [[fever]], such as:<ref name="pmid18466428">{{cite journal |vauthors=Rohr JC, Wagner HJ, Lauten M, Wacker HH, Jüttner E, Hanke C, Pohl M, Niemeyer CM |title=Differentiation of EBV-induced post-transplant Hodgkin lymphoma from Hodgkin-like post-transplant lymphoproliferative disease |journal=Pediatr Transplant |volume=12 |issue=4 |pages=426–31 |date=June 2008 |pmid=18466428 |doi=10.1111/j.1399-3046.2007.00816.x |url=}}</ref>  
*Post transplant lymphoproliferative disorder must be differentiated from other diseases that cause [[fatigue]], [[weight-loss]], and [[fever]], such as:<ref name="pmid18466428">{{cite journal |vauthors=Rohr JC, Wagner HJ, Lauten M, Wacker HH, Jüttner E, Hanke C, Pohl M, Niemeyer CM |title=Differentiation of EBV-induced post-transplant Hodgkin lymphoma from Hodgkin-like post-transplant lymphoproliferative disease |journal=Pediatr Transplant |volume=12 |issue=4 |pages=426–31 |date=June 2008 |pmid=18466428 |doi=10.1111/j.1399-3046.2007.00816.x |url=}}</ref>
*[[Infectious mononucleosis]]  
*[[Infectious mononucleosis]]  
*Diffuse [[large B-cell lymphoma]]  
*Diffuse [[large B-cell lymphoma]]  
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=== '''Incidence''' ===
=== '''Incidence''' ===
* The [[incidence]] of post transplant lymphoproliferative disorder is approximately 20 percent of all cancers especially with solid organ transplantation.<ref name="pmid7779838">{{cite journal |vauthors=Walker RC, Paya CV, Marshall WF, Strickler JG, Wiesner RH, Velosa JA, Habermann TM, Daly RC, McGregor CG |title=Pretransplantation seronegative Epstein-Barr virus status is the primary risk factor for posttransplantation lymphoproliferative disorder in adult heart, lung, and other solid organ transplantations |journal=J. Heart Lung Transplant. |volume=14 |issue=2 |pages=214–21 |date=1995 |pmid=7779838 |doi= |url=}}</ref><ref name="pmid14555552">{{cite journal |vauthors=Reams BD, McAdams HP, Howell DN, Steele MP, Davis RD, Palmer SM |title=Posttransplant lymphoproliferative disorder: incidence, presentation, and response to treatment in lung transplant recipients |journal=Chest |volume=124 |issue=4 |pages=1242–9 |date=October 2003 |pmid=14555552 |doi= |url=}}</ref><ref name="pmid14520450">{{cite journal |vauthors=Adami J, Gäbel H, Lindelöf B, Ekström K, Rydh B, Glimelius B, Ekbom A, Adami HO, Granath F |title=Cancer risk following organ transplantation: a nationwide cohort study in Sweden |journal=Br. J. Cancer |volume=89 |issue=7 |pages=1221–7 |date=October 2003 |pmid=14520450 |pmc=2394311 |doi=10.1038/sj.bjc.6601219 |url=}}</ref><ref name="pmid23222821">{{cite journal |vauthors=Morton M, Coupes B, Roberts SA, Klapper PE, Byers RJ, Vallely PJ, Ryan K, Picton ML |title=Epidemiology of posttransplantation lymphoproliferative disorder in adult renal transplant recipients |journal=Transplantation |volume=95 |issue=3 |pages=470–8 |date=February 2013 |pmid=23222821 |doi=10.1097/TP.0b013e318276a237 |url=}}</ref><ref name="pmid9346628">{{cite journal |vauthors=Penn I |title=Posttransplantation de novo tumors in liver allograft recipients |journal=Liver Transpl Surg |volume=2 |issue=1 |pages=52–9 |date=January 1996 |pmid=9346628 |doi= |url=}}</ref><ref name="PetraraGiunco2015">{{cite journal|last1=Petrara|first1=Maria Raffaella|last2=Giunco|first2=Silvia|last3=Serraino|first3=Diego|last4=Dolcetti|first4=Riccardo|last5=De Rossi|first5=Anita|title=Post-transplant lymphoproliferative disorders: From epidemiology to pathogenesis-driven treatment|journal=Cancer Letters|volume=369|issue=1|year=2015|pages=37–44|issn=03043835|doi=10.1016/j.canlet.2015.08.007}}</ref>
* The [[incidence]] of post transplant lymphoproliferative disorder is approximately 20,000 in 100,000 of all cancers especially with solid organ transplantation.<ref name="pmid7779838">{{cite journal |vauthors=Walker RC, Paya CV, Marshall WF, Strickler JG, Wiesner RH, Velosa JA, Habermann TM, Daly RC, McGregor CG |title=Pretransplantation seronegative Epstein-Barr virus status is the primary risk factor for posttransplantation lymphoproliferative disorder in adult heart, lung, and other solid organ transplantations |journal=J. Heart Lung Transplant. |volume=14 |issue=2 |pages=214–21 |date=1995 |pmid=7779838 |doi= |url=}}</ref><ref name="pmid14555552">{{cite journal |vauthors=Reams BD, McAdams HP, Howell DN, Steele MP, Davis RD, Palmer SM |title=Posttransplant lymphoproliferative disorder: incidence, presentation, and response to treatment in lung transplant recipients |journal=Chest |volume=124 |issue=4 |pages=1242–9 |date=October 2003 |pmid=14555552 |doi= |url=}}</ref><ref name="pmid14520450">{{cite journal |vauthors=Adami J, Gäbel H, Lindelöf B, Ekström K, Rydh B, Glimelius B, Ekbom A, Adami HO, Granath F |title=Cancer risk following organ transplantation: a nationwide cohort study in Sweden |journal=Br. J. Cancer |volume=89 |issue=7 |pages=1221–7 |date=October 2003 |pmid=14520450 |pmc=2394311 |doi=10.1038/sj.bjc.6601219 |url=}}</ref><ref name="pmid23222821">{{cite journal |vauthors=Morton M, Coupes B, Roberts SA, Klapper PE, Byers RJ, Vallely PJ, Ryan K, Picton ML |title=Epidemiology of posttransplantation lymphoproliferative disorder in adult renal transplant recipients |journal=Transplantation |volume=95 |issue=3 |pages=470–8 |date=February 2013 |pmid=23222821 |doi=10.1097/TP.0b013e318276a237 |url=}}</ref><ref name="pmid9346628">{{cite journal |vauthors=Penn I |title=Posttransplantation de novo tumors in liver allograft recipients |journal=Liver Transpl Surg |volume=2 |issue=1 |pages=52–9 |date=January 1996 |pmid=9346628 |doi= |url=}}</ref><ref name="PetraraGiunco2015">{{cite journal|last1=Petrara|first1=Maria Raffaella|last2=Giunco|first2=Silvia|last3=Serraino|first3=Diego|last4=Dolcetti|first4=Riccardo|last5=De Rossi|first5=Anita|title=Post-transplant lymphoproliferative disorders: From epidemiology to pathogenesis-driven treatment|journal=Cancer Letters|volume=369|issue=1|year=2015|pages=37–44|issn=03043835|doi=10.1016/j.canlet.2015.08.007}}</ref>
* The [[incidence]] of post transplant lymphoproliferative disorder in [[liver]] transplants is approximately 1 to 2 percent.
* The [[incidence]] of post transplant lymphoproliferative disorder in [[liver]] transplants is approximately 1000 to 2000 in 100,000 patients.
* The [[incidence]] of post transplant lymphoproliferative disorder in [[renal]] transplant is approximately 1 to 3 percent.
* The [[incidence]] of post transplant lymphoproliferative disorder in [[renal]] transplant is approximately 1000 to 3000 in 100,000 patients.
* The [[incidence]] of post transplant lymphoproliferative disorder in [[heart]] transplant is approximately 2 to 6 percent.
* The [[incidence]] of post transplant lymphoproliferative disorder in [[heart]] transplant is approximately 2000 to 6000 in 100,000 patients.
* The [[incidence]] of post transplant lymphoproliferative disorder in [[lung]] transplant is approximately 2 to 9 percent.
* The [[incidence]] of post transplant lymphoproliferative disorder in [[lung]] transplant is approximately 2000 to 9000 in 100,000 patients.
* The [[incidence]] of post transplant lymphoproliferative disorder in  [[Intestine|intestinal]] or multi organ transplants is approximately as high as 11 to 33 percent.
* The [[incidence]] of post transplant lymphoproliferative disorder in  [[Intestine|intestinal]] or multi organ transplants is approximately as high as 11,000 to 33,000 in 100,000 patients.


=== Prevalence ===
=== Prevalence ===
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===Age===
===Age===
*Post transplant lymphoproliferative disorder is more commonly observed among young patients.<ref name="PetraraGiunco20152">{{cite journal|last1=Petrara|first1=Maria Raffaella|last2=Giunco|first2=Silvia|last3=Serraino|first3=Diego|last4=Dolcetti|first4=Riccardo|last5=De Rossi|first5=Anita|title=Post-transplant lymphoproliferative disorders: From epidemiology to pathogenesis-driven treatment|journal=Cancer Letters|volume=369|issue=1|year=2015|pages=37–44|issn=03043835|doi=10.1016/j.canlet.2015.08.007}}</ref>  
*Post transplant lymphoproliferative disorder is more commonly observed among young patients.<ref name="PetraraGiunco20152">{{cite journal|last1=Petrara|first1=Maria Raffaella|last2=Giunco|first2=Silvia|last3=Serraino|first3=Diego|last4=Dolcetti|first4=Riccardo|last5=De Rossi|first5=Anita|title=Post-transplant lymphoproliferative disorders: From epidemiology to pathogenesis-driven treatment|journal=Cancer Letters|volume=369|issue=1|year=2015|pages=37–44|issn=03043835|doi=10.1016/j.canlet.2015.08.007}}</ref>
   
   
===Gender===
===Gender===
*Females are slightly more affected with post transplant lymphoproliferative disorder than men.<ref name="LaCasce20062">{{cite journal|last1=LaCasce|first1=A. S.|title=Post-Transplant Lymphoproliferative Disorders|journal=The Oncologist|volume=11|issue=6|year=2006|pages=674–680|issn=1083-7159|doi=10.1634/theoncologist.11-6-674}}</ref>
*Females are slightly more affected with post transplant lymphoproliferative disorder than men.<ref name="LaCasce20062">{{cite journal|last1=LaCasce|first1=A. S.|title=Post-Transplant Lymphoproliferative Disorders|journal=The Oncologist|volume=11|issue=6|year=2006|pages=674–680|issn=1083-7159|doi=10.1634/theoncologist.11-6-674}}</ref>


===Race===
===Race===
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**[[Cyclosporine]] use.
**[[Cyclosporine]] use.
**[[Tacrolimus]] use.
**[[Tacrolimus]] use.
**Induction [[therapy]]
**Induction [[therapy]].
**The degree and duration of [[immunosuppression]] plays a very important role in the risk of developing PTLD.
**The degree and duration of [[immunosuppression]] plays a very important role in the risk of developing PTLD.
**[[Epstein Barr virus|EBV]] infection from grafted [[B lymphocyte]]<nowiki/>s.
**[[Epstein Barr virus|EBV]] infection from grafted [[B lymphocyte]]<nowiki/>s.
**Latent [[Epstein Barr virus|EBV]] infection leads to malignancies like
**Latent [[Epstein Barr virus|EBV]] infection leads to malignancies like:
***[[HIV]]-associated [[lymphomas]]
***[[HIV]]-associated [[lymphomas]].
***[[Endemic]] [[Burkitt's lymphoma|Burkitt’s]] lymphoma and
***[[Endemic]] [[Burkitt's lymphoma|Burkitt’s]] lymphoma.
***[[Hodgkin's lymphoma|Hodgkin’s]] lymphoma  
***[[Hodgkin's lymphoma|Hodgkin’s]] lymphoma.
**
**
**
**
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=== Prognosis ===
=== Prognosis ===
* Depending on the extent of the disease progression at the time of [[diagnosis]], the [[prognosis]] may vary in post transplant lymphoproliferative disorder patients due to [[heterogeneity]] of the disease.<ref name="LeblondDhedin2001">{{cite journal|last1=Leblond|first1=Véronique|last2=Dhedin|first2=Nathalie|last3=Bruneel|first3=Marie-France Mamzer|last4=Choquet|first4=Sylvain|last5=Hermine|first5=Olivier|last6=Porcher|first6=Raphaël|last7=Quoc|first7=Stéphanie Nguyen|last8=Davi|first8=Frédéric|last9=Charlotte|first9=Frédéric|last10=Dorent|first10=Richard|last11=Barrou|first11=Benoit|last12=Vernant|first12=Jean-Paul|last13=Raphael|first13=Martine|last14=Levy|first14=Vincent|title=Identification of Prognostic Factors in 61 Patients With Posttransplantation Lymphoproliferative Disorders|journal=Journal of Clinical Oncology|volume=19|issue=3|year=2001|pages=772–778|issn=0732-183X|doi=10.1200/JCO.2001.19.3.772}}</ref><ref name="pmid20085936">{{cite journal |vauthors=Evens AM, David KA, Helenowski I, Nelson B, Kaufman D, Kircher SM, Gimelfarb A, Hattersley E, Mauro LA, Jovanovic B, Chadburn A, Stiff P, Winter JN, Mehta J, Van Besien K, Gregory S, Gordon LI, Shammo JM, Smith SE, Smith SM |title=Multicenter analysis of 80 solid organ transplantation recipients with post-transplantation lymphoproliferative disease: outcomes and prognostic factors in the modern era |journal=J. Clin. Oncol. |volume=28 |issue=6 |pages=1038–46 |date=February 2010 |pmid=20085936 |pmc=2834429 |doi=10.1200/JCO.2009.25.4961 |url=}}</ref>
* Depending on the extent of the disease progression at the time of [[diagnosis]], the [[prognosis]] may vary in post transplant lymphoproliferative disorder patients due to [[heterogeneity]] of the disease.<ref name="LeblondDhedin2001">{{cite journal|last1=Leblond|first1=Véronique|last2=Dhedin|first2=Nathalie|last3=Bruneel|first3=Marie-France Mamzer|last4=Choquet|first4=Sylvain|last5=Hermine|first5=Olivier|last6=Porcher|first6=Raphaël|last7=Quoc|first7=Stéphanie Nguyen|last8=Davi|first8=Frédéric|last9=Charlotte|first9=Frédéric|last10=Dorent|first10=Richard|last11=Barrou|first11=Benoit|last12=Vernant|first12=Jean-Paul|last13=Raphael|first13=Martine|last14=Levy|first14=Vincent|title=Identification of Prognostic Factors in 61 Patients With Posttransplantation Lymphoproliferative Disorders|journal=Journal of Clinical Oncology|volume=19|issue=3|year=2001|pages=772–778|issn=0732-183X|doi=10.1200/JCO.2001.19.3.772}}</ref><ref name="pmid20085936">{{cite journal |vauthors=Evens AM, David KA, Helenowski I, Nelson B, Kaufman D, Kircher SM, Gimelfarb A, Hattersley E, Mauro LA, Jovanovic B, Chadburn A, Stiff P, Winter JN, Mehta J, Van Besien K, Gregory S, Gordon LI, Shammo JM, Smith SE, Smith SM |title=Multicenter analysis of 80 solid organ transplantation recipients with post-transplantation lymphoproliferative disease: outcomes and prognostic factors in the modern era |journal=J. Clin. Oncol. |volume=28 |issue=6 |pages=1038–46 |date=February 2010 |pmid=20085936 |pmc=2834429 |doi=10.1200/JCO.2009.25.4961 |url=}}</ref>
* [[Prognosis]] also depends on what type of PTLD the patient is presenting with.
* [[Prognosis]] also depends on what type of PTLD the patient is presenting.


*[[Prognosis]] is generally poor, and the 5-year survival rate of patients with post transplant lymphoproliferative disorder is approximately 37- 61%.
*[[Prognosis]] is generally poor, and the 5-year survival rate of patients with post transplant lymphoproliferative disorder is approximately 37- 61%.
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*Patients with post transplant lymphoproliferative disorder usually appear pale and malnourished.<ref name="pmid15979320">{{cite journal |vauthors=Taylor AL, Marcus R, Bradley JA |title=Post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation |journal=Crit. Rev. Oncol. Hematol. |volume=56 |issue=1 |pages=155–67 |year=2005 |pmid=15979320 |doi=10.1016/j.critrevonc.2005.03.015 |url=}}</ref>
*Patients with post transplant lymphoproliferative disorder usually appear pale and malnourished.<ref name="pmid15979320">{{cite journal |vauthors=Taylor AL, Marcus R, Bradley JA |title=Post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation |journal=Crit. Rev. Oncol. Hematol. |volume=56 |issue=1 |pages=155–67 |year=2005 |pmid=15979320 |doi=10.1016/j.critrevonc.2005.03.015 |url=}}</ref>
*Physical examination may be remarkable for:<ref name="pmid2845789">{{cite journal |vauthors=Nalesnik MA, Jaffe R, Starzl TE, Demetris AJ, Porter K, Burnham JA, Makowka L, Ho M, Locker J |title=The pathology of posttransplant lymphoproliferative disorders occurring in the setting of cyclosporine A-prednisone immunosuppression |journal=Am. J. Pathol. |volume=133 |issue=1 |pages=173–92 |date=October 1988 |pmid=2845789 |pmc=1880655 |doi= |url=}}</ref>
*Physical examination may be remarkable for:<ref name="pmid2845789">{{cite journal |vauthors=Nalesnik MA, Jaffe R, Starzl TE, Demetris AJ, Porter K, Burnham JA, Makowka L, Ho M, Locker J |title=The pathology of posttransplant lymphoproliferative disorders occurring in the setting of cyclosporine A-prednisone immunosuppression |journal=Am. J. Pathol. |volume=133 |issue=1 |pages=173–92 |date=October 1988 |pmid=2845789 |pmc=1880655 |doi= |url=}}</ref>
**Swelling in the [[Lymph node|lymph nodes]] in the [[neck]] or underarms
**Swelling in the [[Lymph node|lymph nodes]] in the [[neck]] or underarms.
**Patients present with extranodal [[Mass|masses]], especially in area like:<ref name="pmid9457207">{{cite journal |vauthors=Rappaport DC, Chamberlain DW, Shepherd FA, Hutcheon MA |title=Lymphoproliferative disorders after lung transplantation: imaging features |journal=Radiology |volume=206 |issue=2 |pages=519–24 |date=February 1998 |pmid=9457207 |doi=10.1148/radiology.206.2.9457207 |url=}}</ref><ref name="pmid2547308">{{cite journal |vauthors=Randhawa PS, Yousem SA, Paradis IL, Dauber JA, Griffith BP, Locker J |title=The clinical spectrum, pathology, and clonal analysis of Epstein-Barr virus-associated lymphoproliferative disorders in heart-lung transplant recipients |journal=Am. J. Clin. Pathol. |volume=92 |issue=2 |pages=177–85 |date=August 1989 |pmid=2547308 |doi= |url=}}</ref>
**Patients present with extranodal [[Mass|masses]], especially in areas like:<ref name="pmid9457207">{{cite journal |vauthors=Rappaport DC, Chamberlain DW, Shepherd FA, Hutcheon MA |title=Lymphoproliferative disorders after lung transplantation: imaging features |journal=Radiology |volume=206 |issue=2 |pages=519–24 |date=February 1998 |pmid=9457207 |doi=10.1148/radiology.206.2.9457207 |url=}}</ref><ref name="pmid2547308">{{cite journal |vauthors=Randhawa PS, Yousem SA, Paradis IL, Dauber JA, Griffith BP, Locker J |title=The clinical spectrum, pathology, and clonal analysis of Epstein-Barr virus-associated lymphoproliferative disorders in heart-lung transplant recipients |journal=Am. J. Clin. Pathol. |volume=92 |issue=2 |pages=177–85 |date=August 1989 |pmid=2547308 |doi= |url=}}</ref>
***[[Gastrointestinal tract]]([[small intestine]] and [[large bowel]])
***[[Gastrointestinal tract]]([[small intestine]] and [[large bowel]]).
***[[lungs]]
***[[lungs]].
***[[Central nervous system]]
***[[Central nervous system]].
**[[Fever]]
**[[Fever]].
**[[Sleep hyperhidrosis|Night sweats]]
**[[Sleep hyperhidrosis|Night sweats]].
**Unexplained [[weight loss]]
**Unexplained [[weight loss]].
=== Laboratory Findings ===
=== Laboratory Findings ===
[[Laboratory]] findings consistent with the [[diagnosis]] of post transplant lymphoproliferative disorder include:
[[Laboratory]] findings consistent with the [[diagnosis]] of post transplant lymphoproliferative disorder include:
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* In post transplant lymphoproliferative disorder patients [[viral load]] can be measured by [[polymerase chain reaction]] ([[PCR]]).<ref name="pmid10994552">{{cite journal |vauthors=Wagner HJ, Jabs W, Smets F, Wessel M, Fischer L, Offner G, Kirchner H, Bucsky P |title=Real-time polymerase chain reaction (RQ-PCR) for the monitoring of Epstein-Barr virus (EBV) load in peripheral blood mononuclear cells |journal=Klin Padiatr |volume=212 |issue=4 |pages=206–10 |date=2000 |pmid=10994552 |doi=10.1055/s-2000-9678 |url=}}</ref>
* In post transplant lymphoproliferative disorder patients [[viral load]] can be measured by [[polymerase chain reaction]] ([[PCR]]).<ref name="pmid10994552">{{cite journal |vauthors=Wagner HJ, Jabs W, Smets F, Wessel M, Fischer L, Offner G, Kirchner H, Bucsky P |title=Real-time polymerase chain reaction (RQ-PCR) for the monitoring of Epstein-Barr virus (EBV) load in peripheral blood mononuclear cells |journal=Klin Padiatr |volume=212 |issue=4 |pages=206–10 |date=2000 |pmid=10994552 |doi=10.1055/s-2000-9678 |url=}}</ref>


* [[Complete blood count]] which shows Viral load measurement
* [[Complete blood count]] which shows viral load measurement:
** [[Anemia]]
** [[Anemia]].
** [[Thrombocytopenia]] and
** [[Thrombocytopenia]].
** [[Leukopenia]]
** [[Leukopenia]].
* Increased [[Lactate dehydrogenase|LDH]]
* Increased [[Lactate dehydrogenase|LDH]].
* Increased [[calcium]]
* Increased [[calcium]].
* Increased [[uric acid]]
* Increased [[uric acid]].
* [[Urine]] analysis for monoclonal [[protein]]<ref name="pmid11520779">{{cite journal |vauthors=Lemoine A, Pham P, Azoulay D, Saliba F, Emile JF, Saffroy R, Broet P, Bismuth H, Samuel D, Debuire B |title=Detection of gammopathy by serum protein electrophoresis for predicting and managing therapy of lymphoproliferative disorder in 911 recipients of liver transplants |journal=Blood |volume=98 |issue=5 |pages=1332–8 |date=September 2001 |pmid=11520779 |doi= |url=}}</ref><ref name="pmid9346679">{{cite journal |vauthors=Badley AD, Portela DF, Patel R, Kyle RA, Habermann TM, Strickler JG, Ilstrup DM, Wiesner RH, de Groen P, Walker RC, Paya CV |title=Development of monoclonal gammopathy precedes the development of Epstein-Barr virus-induced posttransplant lymphoproliferative disorder |journal=Liver Transpl Surg |volume=2 |issue=5 |pages=375–82 |date=September 1996 |pmid=9346679 |doi= |url=}}</ref><ref name="pmid9484759">{{cite journal |vauthors=Pageaux GP, Bonnardet A, Picot MC, Perrigault PF, Coste V, Navarro F, Fabre JM, Domergue J, Descomps B, Blanc P, Michel H, Larrey D |title=Prevalence of monoclonal immunoglobulins after liver transplantation: relationship with posttransplant lymphoproliferative disorders |journal=Transplantation |volume=65 |issue=3 |pages=397–400 |date=February 1998 |pmid=9484759 |doi= |url=}}</ref>
* [[Urine]] analysis for monoclonal [[protein]].<ref name="pmid11520779">{{cite journal |vauthors=Lemoine A, Pham P, Azoulay D, Saliba F, Emile JF, Saffroy R, Broet P, Bismuth H, Samuel D, Debuire B |title=Detection of gammopathy by serum protein electrophoresis for predicting and managing therapy of lymphoproliferative disorder in 911 recipients of liver transplants |journal=Blood |volume=98 |issue=5 |pages=1332–8 |date=September 2001 |pmid=11520779 |doi= |url=}}</ref><ref name="pmid9346679">{{cite journal |vauthors=Badley AD, Portela DF, Patel R, Kyle RA, Habermann TM, Strickler JG, Ilstrup DM, Wiesner RH, de Groen P, Walker RC, Paya CV |title=Development of monoclonal gammopathy precedes the development of Epstein-Barr virus-induced posttransplant lymphoproliferative disorder |journal=Liver Transpl Surg |volume=2 |issue=5 |pages=375–82 |date=September 1996 |pmid=9346679 |doi= |url=}}</ref><ref name="pmid9484759">{{cite journal |vauthors=Pageaux GP, Bonnardet A, Picot MC, Perrigault PF, Coste V, Navarro F, Fabre JM, Domergue J, Descomps B, Blanc P, Michel H, Larrey D |title=Prevalence of monoclonal immunoglobulins after liver transplantation: relationship with posttransplant lymphoproliferative disorders |journal=Transplantation |volume=65 |issue=3 |pages=397–400 |date=February 1998 |pmid=9484759 |doi= |url=}}</ref>


*
*
Line 195: Line 195:
===Imaging Findings===
===Imaging Findings===
*[[Fluorodeoxyglucose]] ([[Fluorodeoxyglucose|FDG]])-[[positron emission tomography]] ([[PET]]) may be helpful in the [[diagnosis]] of post transplant lymphoproliferative disorder which helps in the following:<ref name="pmid17291214">{{cite journal |vauthors=Bakker NA, van Imhoff GW, Verschuuren EA, van Son WJ |title=Presentation and early detection of post-transplant lymphoproliferative disorder after solid organ transplantation |journal=Transpl. Int. |volume=20 |issue=3 |pages=207–18 |date=March 2007 |pmid=17291214 |doi=10.1111/j.1432-2277.2006.00416.x |url=}}</ref><ref name="CamachoMoreno2014">{{cite journal|last1=Camacho|first1=Juan C.|last2=Moreno|first2=Courtney Coursey|last3=Harri|first3=Peter A.|last4=Aguirre|first4=Diego A.|last5=Torres|first5=William E.|last6=Mittal|first6=Pardeep K.|title=Posttransplantation Lymphoproliferative Disease: Proposed Imaging Classification|journal=RadioGraphics|volume=34|issue=7|year=2014|pages=2025–2038|issn=0271-5333|doi=10.1148/rg.347130130}}</ref><ref name="TaylorMarcus20052">{{cite journal|last1=Taylor|first1=Anna L.|last2=Marcus|first2=Robert|last3=Bradley|first3=J. Andrew|title=Post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation|journal=Critical Reviews in Oncology/Hematology|volume=56|issue=1|year=2005|pages=155–167|issn=10408428|doi=10.1016/j.critrevonc.2005.03.015}}</ref>
*[[Fluorodeoxyglucose]] ([[Fluorodeoxyglucose|FDG]])-[[positron emission tomography]] ([[PET]]) may be helpful in the [[diagnosis]] of post transplant lymphoproliferative disorder which helps in the following:<ref name="pmid17291214">{{cite journal |vauthors=Bakker NA, van Imhoff GW, Verschuuren EA, van Son WJ |title=Presentation and early detection of post-transplant lymphoproliferative disorder after solid organ transplantation |journal=Transpl. Int. |volume=20 |issue=3 |pages=207–18 |date=March 2007 |pmid=17291214 |doi=10.1111/j.1432-2277.2006.00416.x |url=}}</ref><ref name="CamachoMoreno2014">{{cite journal|last1=Camacho|first1=Juan C.|last2=Moreno|first2=Courtney Coursey|last3=Harri|first3=Peter A.|last4=Aguirre|first4=Diego A.|last5=Torres|first5=William E.|last6=Mittal|first6=Pardeep K.|title=Posttransplantation Lymphoproliferative Disease: Proposed Imaging Classification|journal=RadioGraphics|volume=34|issue=7|year=2014|pages=2025–2038|issn=0271-5333|doi=10.1148/rg.347130130}}</ref><ref name="TaylorMarcus20052">{{cite journal|last1=Taylor|first1=Anna L.|last2=Marcus|first2=Robert|last3=Bradley|first3=J. Andrew|title=Post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation|journal=Critical Reviews in Oncology/Hematology|volume=56|issue=1|year=2005|pages=155–167|issn=10408428|doi=10.1016/j.critrevonc.2005.03.015}}</ref>
**[[Staging (pathology)|Staging]]  
**[[Staging (pathology)|Staging]].
**Response evaluation of [[malignant lymphoma]]
**Response evaluation of [[malignant lymphoma]].
**Early [[diagnosis]]
**Early [[diagnosis]].
*[[Computed tomography]] ([[CT]]) or [[magnetic resonance imaging]] ([[Magnetic resonance imaging|MRI]]) may be helpful in the diagnosis of post transplant lymphoproliferative disorder in finding any abnormal [[Nodal (protein)|nodal]] or extranodal masses.<ref name="VrachliotisVaswani2000">{{cite journal|last1=Vrachliotis|first1=Thomas G.|last2=Vaswani|first2=Kuldeep K.|last3=Davies|first3=Elizabeth A.|last4=Elkhammas|first4=Elmahdi A.|last5=Bennett|first5=William F.|last6=Bova|first6=James G.|title=CT Findings in Posttransplantation Lymphoproliferative Disorder of Renal Transplants|journal=American Journal of Roentgenology|volume=175|issue=1|year=2000|pages=183–188|issn=0361-803X|doi=10.2214/ajr.175.1.1750183}}</ref><ref name="CamachoMoreno20142">{{cite journal|last1=Camacho|first1=Juan C.|last2=Moreno|first2=Courtney Coursey|last3=Harri|first3=Peter A.|last4=Aguirre|first4=Diego A.|last5=Torres|first5=William E.|last6=Mittal|first6=Pardeep K.|title=Posttransplantation Lymphoproliferative Disease: Proposed Imaging Classification|journal=RadioGraphics|volume=34|issue=7|year=2014|pages=2025–2038|issn=0271-5333|doi=10.1148/rg.347130130}}</ref>
*[[Computed tomography]] ([[CT]]) or [[magnetic resonance imaging]] ([[Magnetic resonance imaging|MRI]]) may be helpful in the diagnosis of post transplant lymphoproliferative disorder in finding any abnormal [[Nodal (protein)|nodal]] or extranodal masses.<ref name="VrachliotisVaswani2000">{{cite journal|last1=Vrachliotis|first1=Thomas G.|last2=Vaswani|first2=Kuldeep K.|last3=Davies|first3=Elizabeth A.|last4=Elkhammas|first4=Elmahdi A.|last5=Bennett|first5=William F.|last6=Bova|first6=James G.|title=CT Findings in Posttransplantation Lymphoproliferative Disorder of Renal Transplants|journal=American Journal of Roentgenology|volume=175|issue=1|year=2000|pages=183–188|issn=0361-803X|doi=10.2214/ajr.175.1.1750183}}</ref><ref name="CamachoMoreno20142">{{cite journal|last1=Camacho|first1=Juan C.|last2=Moreno|first2=Courtney Coursey|last3=Harri|first3=Peter A.|last4=Aguirre|first4=Diego A.|last5=Torres|first5=William E.|last6=Mittal|first6=Pardeep K.|title=Posttransplantation Lymphoproliferative Disease: Proposed Imaging Classification|journal=RadioGraphics|volume=34|issue=7|year=2014|pages=2025–2038|issn=0271-5333|doi=10.1148/rg.347130130}}</ref>


== Treatment ==
== Treatment ==
=== Medical Therapy ===
=== Medical Therapy ===
* Pharmacologic medical therapies for post transplant lymphoproliferative disorder highly varied based on the subtype and type of [[transplant]].<ref name="pmid11422823">{{cite journal |vauthors=Allen U, Hébert D, Moore D, Dror Y, Wasfy S |title=Epstein-Barr virus-related post-transplant lymphoproliferative disease in solid organ transplant recipients, 1988-97: a Canadian multi-centre experience |journal=Pediatr Transplant |volume=5 |issue=3 |pages=198–203 |date=June 2001 |pmid=11422823 |doi= |url=}}</ref>  
* According to following guidelines proposed post transplant lymphoproliferative disease is treated:<ref name="pmid204088483">{{cite journal |vauthors=Parker A, Bowles K, Bradley JA, Emery V, Featherstone C, Gupte G, Marcus R, Parameshwar J, Ramsay A, Newstead C |title=Management of post-transplant lymphoproliferative disorder in adult solid organ transplant recipients - BCSH and BTS Guidelines |journal=Br. J. Haematol. |volume=149 |issue=5 |pages=693–705 |date=June 2010 |pmid=20408848 |doi=10.1111/j.1365-2141.2010.08160.x |url=}}</ref><ref name="pmid29021921">{{cite journal |vauthors=Bishnoi R, Bajwa R, Franke AJ, Skelton WP, Wang Y, Patel NM, Slayton WB, Zou F, Dang NH |title=Post-transplant lymphoproliferative disorder (PTLD): single institutional experience of 141 patients |journal=Exp Hematol Oncol |volume=6 |issue= |pages=26 |date=2017 |pmid=29021921 |pmc=5622441 |doi=10.1186/s40164-017-0087-0 |url=}}</ref><ref name="DierickxTousseyn2015">{{cite journal|last1=Dierickx|first1=D.|last2=Tousseyn|first2=T.|last3=Gheysens|first3=O.|title=How I treat posttransplant lymphoproliferative disorders|journal=Blood|volume=126|issue=20|year=2015|pages=2274–2283|issn=0006-4971|doi=10.1182/blood-2015-05-615872}}</ref><ref name="BlumbergDanziger-Isakov2013">{{cite journal|last1=Blumberg|first1=Emily A.|last2=Danziger-Isakov|first2=Lara|last3=Kumar|first3=Deepali|last4=Michaels|first4=Marian G.|last5=Razonable|first5=Raymund R.|title=Foreword: Guidelines 3|journal=American Journal of Transplantation|volume=13|issue=s4|year=2013|pages=1–2|issn=16006135|doi=10.1111/ajt.12129}}</ref><ref name="pmid120916382">{{cite journal |vauthors= |title=European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.6.1. Cancer risk after renal transplantation. Post-transplant lymphoproliferative disease (PTLD): prevention and treatment |journal=Nephrol. Dial. Transplant. |volume=17 Suppl 4 |issue= |pages=31–3, 35–6 |date=2002 |pmid=12091638 |doi= |url=}}</ref>
* In post transplant lymphoproliferative disorder patients standardized therapeutic approach cannot be applied to all patients.
** American Society of Transplantation (AST).
** [[World Health Organization]] ([[World Health Organization|WHO]]).
** NCCN: National Comprehensive Cancer Network.
** European best practice guidelines for renal transplantation.
** British Committee for Standards in Haematology.
** British Transplantation Society.


*The medical treatment for post transplant lymphoproliferative disorder, includes: <ref name="Biomed">BioMed Central. EBV-associated post-transplantation B-cell lymphoproliferative disorder following allogenic stem cell transplantation for acute lymphoblastic leukaemia: tumor regression after reduction of immunosuppression - a case report. https://diagnosticpathology.biomedcentral.com/articles/10.1186/1746-1596-5-21 Accessed on May 23, 2016 </ref>
* Pharmacologic medical therapies for post transplant lymphoproliferative disorder highly varied based on the subtype and type of [[transplant]].<ref name="pmid11422823">{{cite journal |vauthors=Allen U, Hébert D, Moore D, Dror Y, Wasfy S |title=Epstein-Barr virus-related post-transplant lymphoproliferative disease in solid organ transplant recipients, 1988-97: a Canadian multi-centre experience |journal=Pediatr Transplant |volume=5 |issue=3 |pages=198–203 |date=June 2001 |pmid=11422823 |doi= |url=}}</ref>
* In post transplant lymphoproliferative disorder patients standardized [[therapeutic]] approach cannot be applied to all patients.
 
*The medical treatment for post transplant lymphoproliferative disorder, include the followings.<ref name="Biomed">BioMed Central. EBV-associated post-transplantation B-cell lymphoproliferative disorder following allogenic stem cell transplantation for acute lymphoblastic leukaemia: tumor regression after reduction of immunosuppression - a case report. https://diagnosticpathology.biomedcentral.com/articles/10.1186/1746-1596-5-21 Accessed on May 23, 2016 </ref>


==== Immunosuppression ====
==== Immunosuppression ====
* Low-dose [[immunosuppressive]] agents [[protocols]] highly reduce the [[incidence]] of post transplant lymphoproliferative disorder.<ref name="pmid14734884">{{cite journal |vauthors=Ganschow R, Schulz T, Meyer T, Broering DC, Burdelski M |title=Low-dose immunosuppression reduces the incidence of post-transplant lymphoproliferative disease in pediatric liver graft recipients |journal=J. Pediatr. Gastroenterol. Nutr. |volume=38 |issue=2 |pages=198–203 |date=February 2004 |pmid=14734884 |doi= |url=}}</ref>
* Low-dose [[immunosuppressive]] agents [[protocols]] highly reduce the [[incidence]] of post transplant lymphoproliferative disorder.<ref name="pmid14734884">{{cite journal |vauthors=Ganschow R, Schulz T, Meyer T, Broering DC, Burdelski M |title=Low-dose immunosuppression reduces the incidence of post-transplant lymphoproliferative disease in pediatric liver graft recipients |journal=J. Pediatr. Gastroenterol. Nutr. |volume=38 |issue=2 |pages=198–203 |date=February 2004 |pmid=14734884 |doi= |url=}}</ref>
* The mainstay of treatment for post transplant lymphoproliferative disorder is giving lose dose or reduction of the dose of [[immunosuppressive]] agents with the following:<ref name="pmid22241590">{{cite journal |vauthors=Jagadeesh D, Woda BA, Draper J, Evens AM |title=Post transplant lymphoproliferative disorders: risk, classification, and therapeutic recommendations |journal=Curr Treat Options Oncol |volume=13 |issue=1 |pages=122–36 |date=March 2012 |pmid=22241590 |doi=10.1007/s11864-011-0177-x |url=}}</ref><ref name="pmid20963522">{{cite journal |vauthors=Evens AM, Roy R, Sterrenberg D, Moll MZ, Chadburn A, Gordon LI |title=Post-transplantation lymphoproliferative disorders: diagnosis, prognosis, and current approaches to therapy |journal=Curr Oncol Rep |volume=12 |issue=6 |pages=383–94 |date=November 2010 |pmid=20963522 |doi=10.1007/s11912-010-0132-1 |url=}}</ref><ref name="pmid25655616">{{cite journal |vauthors=Singavi AK, Harrington AM, Fenske TS |title=Post-transplant lymphoproliferative disorders |journal=Cancer Treat. Res. |volume=165 |issue= |pages=305–27 |date=2015 |pmid=25655616 |doi=10.1007/978-3-319-13150-4_13 |url=}}</ref><ref name="pmid23737188">{{cite journal |vauthors=Al-Mansour Z, Nelson BP, Evens AM |title=Post-transplant lymphoproliferative disease (PTLD): risk factors, diagnosis, and current treatment strategies |journal=Curr Hematol Malig Rep |volume=8 |issue=3 |pages=173–83 |date=September 2013 |pmid=23737188 |pmc=4831913 |doi=10.1007/s11899-013-0162-5 |url=}}</ref>
* The mainstay of treatment for post transplant lymphoproliferative disorder is giving lose dose or reduction of the dose of [[immunosuppressive]] agents with the following:<ref name="pmid22241590">{{cite journal |vauthors=Jagadeesh D, Woda BA, Draper J, Evens AM |title=Post transplant lymphoproliferative disorders: risk, classification, and therapeutic recommendations |journal=Curr Treat Options Oncol |volume=13 |issue=1 |pages=122–36 |date=March 2012 |pmid=22241590 |doi=10.1007/s11864-011-0177-x |url=}}</ref><ref name="pmid20963522">{{cite journal |vauthors=Evens AM, Roy R, Sterrenberg D, Moll MZ, Chadburn A, Gordon LI |title=Post-transplantation lymphoproliferative disorders: diagnosis, prognosis, and current approaches to therapy |journal=Curr Oncol Rep |volume=12 |issue=6 |pages=383–94 |date=November 2010 |pmid=20963522 |doi=10.1007/s11912-010-0132-1 |url=}}</ref><ref name="pmid25655616">{{cite journal |vauthors=Singavi AK, Harrington AM, Fenske TS |title=Post-transplant lymphoproliferative disorders |journal=Cancer Treat. Res. |volume=165 |issue= |pages=305–27 |date=2015 |pmid=25655616 |doi=10.1007/978-3-319-13150-4_13 |url=}}</ref><ref name="pmid23737188">{{cite journal |vauthors=Al-Mansour Z, Nelson BP, Evens AM |title=Post-transplant lymphoproliferative disease (PTLD): risk factors, diagnosis, and current treatment strategies |journal=Curr Hematol Malig Rep |volume=8 |issue=3 |pages=173–83 |date=September 2013 |pmid=23737188 |pmc=4831913 |doi=10.1007/s11899-013-0162-5 |url=}}</ref><ref name="pmid22173060">{{cite journal |vauthors=Trappe R, Oertel S, Leblond V, Mollee P, Sender M, Reinke P, Neuhaus R, Lehmkuhl H, Horst HA, Salles G, Morschhauser F, Jaccard A, Lamy T, Leithäuser M, Zimmermann H, Anagnostopoulos I, Raphael M, Riess H, Choquet S |title=Sequential treatment with rituximab followed by CHOP chemotherapy in adult B-cell post-transplant lymphoproliferative disorder (PTLD): the prospective international multicentre phase 2 PTLD-1 trial |journal=Lancet Oncol. |volume=13 |issue=2 |pages=196–206 |date=February 2012 |pmid=22173060 |doi=10.1016/S1470-2045(11)70300-X |url=}}</ref><ref name="pmid23771985">{{cite journal |vauthors=Styczynski J, Gil L, Tridello G, Ljungman P, Donnelly JP, van der Velden W, Omar H, Martino R, Halkes C, Faraci M, Theunissen K, Kalwak K, Hubacek P, Sica S, Nozzoli C, Fagioli F, Matthes S, Diaz MA, Migliavacca M, Balduzzi A, Tomaszewska A, Camara Rde L, van Biezen A, Hoek J, Iacobelli S, Einsele H, Cesaro S |title=Response to rituximab-based therapy and risk factor analysis in Epstein Barr Virus-related lymphoproliferative disorder after hematopoietic stem cell transplant in children and adults: a study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation |journal=Clin. Infect. Dis. |volume=57 |issue=6 |pages=794–802 |date=September 2013 |pmid=23771985 |doi=10.1093/cid/cit391 |url=}}</ref>  
** [[rituximab]]
**[[rituximab]].
** [[Chemotherapy]] and  
** [[Chemotherapy]].
** [[Radiation therapy]]
** [[Radiation therapy]].
'''Early Lesions'''
* Pharmacologic medical therapies for early lesions in post transplant lymphoproliferative disorder include:<ref name="pmid12091638">{{cite journal |vauthors= |title=European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.6.1. Cancer risk after renal transplantation. Post-transplant lymphoproliferative disease (PTLD): prevention and treatment |journal=Nephrol. Dial. Transplant. |volume=17 Suppl 4 |issue= |pages=31–3, 35–6 |date=2002 |pmid=12091638 |doi= |url=}}</ref><ref name="pmid204088482">{{cite journal |vauthors=Parker A, Bowles K, Bradley JA, Emery V, Featherstone C, Gupte G, Marcus R, Parameshwar J, Ramsay A, Newstead C |title=Management of post-transplant lymphoproliferative disorder in adult solid organ transplant recipients - BCSH and BTS Guidelines |journal=Br. J. Haematol. |volume=149 |issue=5 |pages=693–705 |date=June 2010 |pmid=20408848 |doi=10.1111/j.1365-2141.2010.08160.x |url=}}</ref>
** Reduction of [[immunosuppression]].
'''Polymorphic PTLD'''
* Pharmacologic medical therapies for polymorphic post transplant lymphoproliferative disorder include:
** Reduction of [[immunosuppression]] with use of [[rituximab]].
'''Monomorphic PTLD'''
* Pharmacologic medical therapies for monomorphic post transplant lymphoproliferative disorder include:<ref name="pmid11374406">{{cite journal |vauthors=Tsai DE, Hardy CL, Tomaszewski JE, Kotloff RM, Oltoff KM, Somer BG, Schuster SJ, Porter DL, Montone KT, Stadtmauer EA |title=Reduction in immunosuppression as initial therapy for posttransplant lymphoproliferative disorder: analysis of prognostic variables and long-term follow-up of 42 adult patients |journal=Transplantation |volume=71 |issue=8 |pages=1076–88 |date=April 2001 |pmid=11374406 |doi= |url=}}</ref>
**[[Rituximab]] with with [[chemotherapy]] and reduction of [[immunosuppression]].
'''Classic Hodgkin lymphoma-like PTLD'''
* Pharmacologic medical therapies for classic hodgkin lymphoma like post transplant lymphoproliferative disorder include:
** [[Chemotherapy]] with or without [[radiation therapy]].
'''Rituximab'''
* When it comes to treatment of post transplant lymphoproliferative disorder patients [[rituximab]] play an important role which produce anti-[[CD20]] [[monoclonal antibodies]].<ref name="pmid16468968">{{cite journal |vauthors=Elstrom RL, Andreadis C, Aqui NA, Ahya VN, Bloom RD, Brozena SC, Olthoff KM, Schuster SJ, Nasta SD, Stadtmauer EA, Tsai DE |title=Treatment of PTLD with rituximab or chemotherapy |journal=Am. J. Transplant. |volume=6 |issue=3 |pages=569–76 |date=March 2006 |pmid=16468968 |doi=10.1111/j.1600-6143.2005.01211.x |url=}}</ref><ref name="pmid10568575">{{cite journal |vauthors=Cook RC, Connors JM, Gascoyne RD, Fradet G, Levy RD |title=Treatment of post-transplant lymphoproliferative disease with rituximab monoclonal antibody after lung transplantation |journal=Lancet |volume=354 |issue=9191 |pages=1698–9 |date=November 1999 |pmid=10568575 |doi=10.1016/S0140-6736(99)02058-9 |url=}}</ref><ref name="pmid11448808">{{cite journal |vauthors=Zilz ND, Olson LJ, McGregor CG |title=Treatment of post-transplant lymphoproliferative disorder with monoclonal CD20 antibody (rituximab) after heart transplantation |journal=J. Heart Lung Transplant. |volume=20 |issue=7 |pages=770–2 |date=July 2001 |pmid=11448808 |doi= |url=}}</ref><ref name="pmid16149091">{{cite journal |vauthors=Blaes AH, Peterson BA, Bartlett N, Dunn DL, Morrison VA |title=Rituximab therapy is effective for posttransplant lymphoproliferative disorders after solid organ transplantation: results of a phase II trial |journal=Cancer |volume=104 |issue=8 |pages=1661–7 |date=October 2005 |pmid=16149091 |doi=10.1002/cncr.21391 |url=}}</ref>
* [[Rituximab]] helps in treatment of following [[non-Hodgkin lymphomas]]:
** [[Diffuse large B cell lymphoma]].
** [[Follicular lymphoma]].
* [[Rituximab]] alone can achieve complete [[Remission (medicine)|remission]] in almost 20% of the patient.<ref name="pmid16254143">{{cite journal |vauthors=Choquet S, Leblond V, Herbrecht R, Socié G, Stoppa AM, Vandenberghe P, Fischer A, Morschhauser F, Salles G, Feremans W, Vilmer E, Peraldi MN, Lang P, Lebranchu Y, Oksenhendler E, Garnier JL, Lamy T, Jaccard A, Ferrant A, Offner F, Hermine O, Moreau A, Fafi-Kremer S, Morand P, Chatenoud L, Berriot-Varoqueaux N, Bergougnoux L, Milpied N |title=Efficacy and safety of rituximab in B-cell post-transplantation lymphoproliferative disorders: results of a prospective multicenter phase 2 study |journal=Blood |volume=107 |issue=8 |pages=3053–7 |date=April 2006 |pmid=16254143 |doi=10.1182/blood-2005-01-0377 |url=}}</ref>
** Preferred regimen (1): [[Rituximab]] 375 mg/m2 per week for four weeks.
'''Chemoimmunotherapy'''
* Chemoimmunotherapy medical therapy is recommended among patients with post transplant lymphoproliferative disorder.<ref name="pmid7579436">{{cite journal |vauthors=Swinnen LJ, Mullen GM, Carr TJ, Costanzo MR, Fisher RI |title=Aggressive treatment for postcardiac transplant lymphoproliferation |journal=Blood |volume=86 |issue=9 |pages=3333–40 |date=November 1995 |pmid=7579436 |doi= |url=}}</ref><ref name="pmid10755561">{{cite journal |vauthors=Smets F, Vajro P, Cornu G, Reding R, Otte JB, Sokal E |title=Indications and results of chemotherapy in children with posttransplant lymphoproliferative disease after liver transplantation |journal=Transplantation |volume=69 |issue=5 |pages=982–4 |date=March 2000 |pmid=10755561 |doi= |url=}}</ref><ref name="pmid11054435">{{cite journal |vauthors=Mamzer-Bruneel MF, Lomé C, Morelon E, Levy V, Bourquelot P, Jacobs F, Gessain A, Mac Intyre E, Brousse N, Kreis H, Hermine O |title=Durable remission after aggressive chemotherapy for very late post-kidney transplant lymphoproliferation: A report of 16 cases observed in a single center |journal=J. Clin. Oncol. |volume=18 |issue=21 |pages=3622–32 |date=November 2000 |pmid=11054435 |doi=10.1200/JCO.2000.18.21.3622 |url=}}</ref><ref name="pmid19451438">{{cite journal |vauthors=Knight JS, Tsodikov A, Cibrik DM, Ross CW, Kaminski MS, Blayney DW |title=Lymphoma after solid organ transplantation: risk, response to therapy, and survival at a transplantation center |journal=J. Clin. Oncol. |volume=27 |issue=20 |pages=3354–62 |date=July 2009 |pmid=19451438 |doi=10.1200/JCO.2008.20.0857 |url=}}</ref>
* Along with chemoimmunotherapy, [[rituximab]] is also added if the patient tested positive for [[CD20]].<ref name="pmid16586109">{{cite journal |vauthors=Oertel S, Trappe RU, Zeidler K, Babel N, Reinke P, Hummel M, Jonas S, Papp-Vary M, Subklewe M, Dörken B, Riess H, Gärtner B |title=Epstein-Barr viral load in whole blood of adults with posttransplant lymphoproliferative disorder after solid organ transplantation does not correlate with clinical course |journal=Ann. Hematol. |volume=85 |issue=7 |pages=478–84 |date=July 2006 |pmid=16586109 |doi=10.1007/s00277-006-0109-1 |url=}}</ref>
* Preferred regimen: [[R-CHOP regimen|R-CHOP]]
** [[Cyclophosphamide]].
** [[Doxorubicin]].
** [[Vincristine]].
** [[Prednisone|Prednisone.]]
* When [[rituximab]] is added to the chemoimmunotherapy regimen the complete [[Remission (medicine)|remission]] rates are estimated approximately to be 65%.
 
*  
*  


Line 218: Line 255:


=== Surgery ===
=== Surgery ===
*Surgery is not recommended for patients with post transplant lymphoproliferative disorder.<ref name="pmid15979320">{{cite journal |vauthors=Taylor AL, Marcus R, Bradley JA |title=Post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation |journal=Crit. Rev. Oncol. Hematol. |volume=56 |issue=1 |pages=155–67 |year=2005 |pmid=15979320 |doi=10.1016/j.critrevonc.2005.03.015 |url=}}</ref>
*[[Surgery]] is not recommended for patients with post transplant lymphoproliferative disorder.<ref name="pmid15979320">{{cite journal |vauthors=Taylor AL, Marcus R, Bradley JA |title=Post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation |journal=Crit. Rev. Oncol. Hematol. |volume=56 |issue=1 |pages=155–67 |year=2005 |pmid=15979320 |doi=10.1016/j.critrevonc.2005.03.015 |url=}}</ref>


=== Prevention ===
=== Prevention ===
*There are no primary preventive measures available for post transplant lymphoproliferative disorder.
*Effective measures for the primary prevention of post transplant lymphoproliferative disorder include:
**Tapering [[Immunosuppressive therapy|immunosuppressive]] therapy.
**[[Antiviral]] [[prophylaxis]] with [[ganciclovir]].
**Pretreatment assessment: check the patient with the following:
***[[Comorbidities]].
***[[Complete blood count|Complete blood picture]].
***[[Liver function tests|LFT]]'s.
***[[Albumin]] levels.
***[[HIV]] status.
***[[Hepatitis]] tests.
***[[EBV]] serology tests.
***


==References==
==References==

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vamsikrishna Gunnam M.B.B.S [2] Maria Fernanda Villarreal, M.D. [3]

Synonyms and keywords: PTLD;

Overview

Post-transplant lymphoproliferative disorder (also known as PTLD) is defined as a lymphoid (immune cells) and/or plasmacytic proliferations (rapid increase) due to therapeutic immunosuppression after organ transplantation especially in the patients who are undergoing solid organ or allogeneic (donor) hematopoietic stem cell transplantation. Post transplant lymphoproliferative disorder was first discovered by Denis Parsons Burkitt, an Irish physician, in 1965. According to World Health Organization (WHO) classification system, post transplant lymphoproliferative disorder may be classified into 4 subtypes: early hyperplastic lesions, polymorphic lesions, monomorphic lesions, and classic Hodgkin-type lymphomas. Patients with post-transplant lymphoproliferative disorder may develop serious complications of transplantation with infectious mononucleosis-like lesions due to Epstein-Barr virus (EBV) or polyclonal polymorphic B-cell hyperplasia. In some cases, B-cells may undergo mutations which will render them malignant, giving rise to a lymphoma. The malignant cell clone can become the dominant proliferating cell type, leading to a group of B cell lymphomas occurring in immunosuppressed patients following organ transplant. Post transplant lymphoproliferative disorder arises from germinal center or post-germinal center B cells (B-PTLD), which are normally involved the production of antibodies and durable memory B cells. Post transplant lymphoproliferative disorder is very rare, and the prevalence of post transplant lymphoproliferative disorder remains unknown. Post transplant lymphoproliferative disorder is more commonly observed among young patients. The medical treatment for post transplant lymphoproliferative disorder, includes: immunosuppression, antiviral therapy, interferon alpha therapy, CD20 antibody therapy, and chemotherapy.

Historical Perspective

  • Post transplant lymphoproliferative disorder was first discovered by Denis Parsons Burkitt, an Irish physician, in 1965.
  • Post transplant lymphoproliferative disorder was first introduced in 1984 by Starzl.[1]

Classification

Category Subtype
Early hyperplastic lesions
Polymorphic lesions
Monomorphic lesions B-cell lymphomas

T-cell lymphomas

Other types

Pathophysiology

  • It is understood that post transplant lymphoproliferative disorder is the result of B cell proliferation induced by Epstein-Barr virus (EBV) infection.[4][5][6]
  • 90 to 95 percent of patients with post transplant lymphoproliferative disorder shows positive serologic of infection especially with Epstein-Barr virus (EBV) infection.[7]
  • Membrane proteins associated with EBV plays a major role in contribute to B cell growth and survival.[8][9][10][11][12][13]
    • LMP-1-Latent membrane protein 1
    • LMP-2A-Latent membrane protein 2
    • EBNA-2 (Epstein-Barr nuclear antigen 2) and
    • EBNA-LP (Epstein-Barr nuclear antigen 2 ladder protein)
  • The overexpression of bcl-2 has been associated with the development of post transplant lymphoproliferative disorder.
  • On gross pathology, characteristic findings of post transplant lymphoproliferative disorder, include:

Causes

Differentiating Post Transplant Lymphoproliferative Disorder from Other Diseases

Epidemiology and Demographics

Incidence

  • The incidence of post transplant lymphoproliferative disorder is approximately 20,000 in 100,000 of all cancers especially with solid organ transplantation.[20][21][22][23][24][25]
  • The incidence of post transplant lymphoproliferative disorder in liver transplants is approximately 1000 to 2000 in 100,000 patients.
  • The incidence of post transplant lymphoproliferative disorder in renal transplant is approximately 1000 to 3000 in 100,000 patients.
  • The incidence of post transplant lymphoproliferative disorder in heart transplant is approximately 2000 to 6000 in 100,000 patients.
  • The incidence of post transplant lymphoproliferative disorder in lung transplant is approximately 2000 to 9000 in 100,000 patients.
  • The incidence of post transplant lymphoproliferative disorder in intestinal or multi organ transplants is approximately as high as 11,000 to 33,000 in 100,000 patients.

Prevalence

  • The prevalence of post transplant lymphoproliferative disorder remains unknown.

Age

  • Post transplant lymphoproliferative disorder is more commonly observed among young patients.[26]

Gender

  • Females are slightly more affected with post transplant lymphoproliferative disorder than men.[27]

Race

  • There is no racial predilection for post transplant lymphoproliferative disorder.[28]

Risk Factors

Natural History, Complications and Prognosis

Natural History

  • The majority of patients with post transplant lymphoproliferative disorder are symptomatic at the time of diagnosis.
  • Early clinical features include fatigue, fever, and weight-loss.

Complications

  • If left untreated, patients with post transplant lymphoproliferative disorder may progress to develop organ failure.
  • The most common complication of post transplant lymphoproliferative disorder is fatal infection.

Prognosis

  • Depending on the extent of the disease progression at the time of diagnosis, the prognosis may vary in post transplant lymphoproliferative disorder patients due to heterogeneity of the disease.[35][36]
  • Prognosis also depends on what type of PTLD the patient is presenting.
  • Prognosis is generally poor, and the 5-year survival rate of patients with post transplant lymphoproliferative disorder is approximately 37- 61%.
  • In post transplant lymphoproliferative disorder patients estimated average survival rates range from 25%–60%.

Diagnosis

Symptoms

  • Symptoms in post transplant lymphoproliferative disorder patients are highly variable.[18]
  • Symptoms are depends on type of post transplant lymphoproliferative disorder patient present with, and the organs involved.
  • Symptoms of post transplant lymphoproliferative disorder may include the following:[37]

Physical Examination

Laboratory Findings

Laboratory findings consistent with the diagnosis of post transplant lymphoproliferative disorder include:

Imaging Findings

Treatment

Medical Therapy

  • According to following guidelines proposed post transplant lymphoproliferative disease is treated:[56][57][58][59][60]
    • American Society of Transplantation (AST).
    • World Health Organization (WHO).
    • NCCN: National Comprehensive Cancer Network.
    • European best practice guidelines for renal transplantation.
    • British Committee for Standards in Haematology.
    • British Transplantation Society.
  • Pharmacologic medical therapies for post transplant lymphoproliferative disorder highly varied based on the subtype and type of transplant.[61]
  • In post transplant lymphoproliferative disorder patients standardized therapeutic approach cannot be applied to all patients.
  • The medical treatment for post transplant lymphoproliferative disorder, include the followings.[62]

Immunosuppression

Early Lesions

  • Pharmacologic medical therapies for early lesions in post transplant lymphoproliferative disorder include:[70][71]

Polymorphic PTLD

  • Pharmacologic medical therapies for polymorphic post transplant lymphoproliferative disorder include:

Monomorphic PTLD

Classic Hodgkin lymphoma-like PTLD

  • Pharmacologic medical therapies for classic hodgkin lymphoma like post transplant lymphoproliferative disorder include:

Rituximab

Chemoimmunotherapy

Surgery

  • Surgery is not recommended for patients with post transplant lymphoproliferative disorder.[18]

Prevention

References

  1. Petrara, Maria Raffaella; Giunco, Silvia; Serraino, Diego; Dolcetti, Riccardo; De Rossi, Anita (2015). "Post-transplant lymphoproliferative disorders: From epidemiology to pathogenesis-driven treatment". Cancer Letters. 369 (1): 37–44. doi:10.1016/j.canlet.2015.08.007. ISSN 0304-3835.
  2. LaCasce, A. S. (2006). "Post-Transplant Lymphoproliferative Disorders". The Oncologist. 11 (6): 674–680. doi:10.1634/theoncologist.11-6-674. ISSN 1083-7159.
  3. Petrara, Maria Raffaella; Giunco, Silvia; Serraino, Diego; Dolcetti, Riccardo; De Rossi, Anita (2015). "Post-transplant lymphoproliferative disorders: From epidemiology to pathogenesis-driven treatment". Cancer Letters. 369 (1): 37–44. doi:10.1016/j.canlet.2015.08.007. ISSN 0304-3835.
  4. Kotton CN, Fishman JA (June 2005). "Viral infection in the renal transplant recipient". J. Am. Soc. Nephrol. 16 (6): 1758–74. doi:10.1681/ASN.2004121113. PMID 15829710.
  5. Patton DF, Wilkowski CW, Hanson CA, Shapiro R, Gajl-Peczalska KJ, Filipovich AH, McClain KL (June 1990). "Epstein-Barr virus--determined clonality in posttransplant lymphoproliferative disease". Transplantation. 49 (6): 1080–4. PMID 2163133.
  6. Taylor AL, Marcus R, Bradley JA (October 2005). "Post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation". Crit. Rev. Oncol. Hematol. 56 (1): 155–67. doi:10.1016/j.critrevonc.2005.03.015. PMID 15979320.
  7. Hanto DW (1995). "Classification of Epstein-Barr virus-associated posttransplant lymphoproliferative diseases: implications for understanding their pathogenesis and developing rational treatment strategies". Annu. Rev. Med. 46: 381–94. doi:10.1146/annurev.med.46.1.381. PMID 7598473.
  8. Mosialos G, Birkenbach M, Yalamanchili R, VanArsdale T, Ware C, Kieff E (February 1995). "The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family". Cell. 80 (3): 389–99. PMID 7859281.
  9. Izumi KM, Kaye KM, Kieff ED (February 1997). "The Epstein-Barr virus LMP1 amino acid sequence that engages tumor necrosis factor receptor associated factors is critical for primary B lymphocyte growth transformation". Proc. Natl. Acad. Sci. U.S.A. 94 (4): 1447–52. PMC 19811. PMID 9037073.
  10. Liebowitz D (May 1998). "Epstein-Barr virus and a cellular signaling pathway in lymphomas from immunosuppressed patients". N. Engl. J. Med. 338 (20): 1413–21. doi:10.1056/NEJM199805143382003. PMID 9580648.
  11. Thorley-Lawson DA (October 2001). "Epstein-Barr virus: exploiting the immune system". Nat. Rev. Immunol. 1 (1): 75–82. doi:10.1038/35095584. PMID 11905817.
  12. Kaiser C, Laux G, Eick D, Jochner N, Bornkamm GW, Kempkes B (May 1999). "The proto-oncogene c-myc is a direct target gene of Epstein-Barr virus nuclear antigen 2". J. Virol. 73 (5): 4481–4. PMC 104340. PMID 10196351.
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