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WHO Classification of Tumours
Post-transplant lymphoproliferative disorders (PTLD)


> Definition
Post-transplant lymphoproliferative disorders (PTLD) are lymphoid or plasmacytic proliferations that develop as a consequence of immunosuppression in a recipient of a solid organ, bone marrow (BM) or stem cell allograft. PTLD comprise a spectrum ranging from usually Epstein-Barr virus (EBV)-driven infectious mononucleosis-type polyclonal proliferations to EBV-positive or EBV-negative proliferations indistinguishable from a subset of B-cell or less often T-cell lymphomas that occur in immuno­competent individuals. The monomorphic and Hodgkin-type PTLD are further categorized as in non-immunosuppressed patients, according to the lymphoma they resemble. Indolent B-cell lymphomas such as follicular lymphoma and MALT lymphoma in allograft recipients are designated as they are in the normal host and not considered a type of PTLD. Detection of rare EBV-positive cells in the absence of an appropriate lymphoid/plasmacytic proliferation is also not considered diagnostic of a PTLD.

There are four major categories of PTLD with important further subcategorization often required as listed in Table 13.02. The varied components of the pathologic evaluation used in the diagnosis and categorization of a PTLD and their specific objectives are summarized in Table 13.03. The criteria for each of the major types of PTLD are summarized in Table 13.04.

> Epidemiology
The characteristics of PTLD appear to differ somewhat from one institution to another, probably as a result of different patient populations, allograft types and immunosuppressive regimens. A variety of risk factors have been identified

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Caillard S, Dharnidharka V, Agodoa L, Bohen E, Abbott K (2005)
Posttransplant lymphoproliferative disorders after renal transplantation in the United States in era of modern immunosuppression.
Transplantation 80: 1233-43




Click to access Pubmed
Caillard S, Lelong C, Pessione F, Moulin B, (2006)
Post-transplant lymphoproliferative disorders occurring after renal transplantation in adults: report of 230 cases from the French Registry.
Am J Transplant 6: 2735-42




Click to access Pubmed
Opelz G, Döhler B (2004)
Lymphomas after solid organ transplantation: a collaborative transplant study report.
Am J Transplant 4: 222-30



, but the most important risk factor for EBV-driven PTLD is EBV sero­negativity at the time of transplantation
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Caillard S, Lelong C, Pessione F, Moulin B, (2006)
Post-transplant lymphoproliferative disorders occurring after renal transplantation in adults: report of 230 cases from the French Registry.
Am J Transplant 6: 2735-42




Click to access Pubmed
Webber SA (1999)
Post-transplant lymphoproliferative disorders: a preventable complication of solid organ transplantation?
Pediatr Transplant 3: 95-9



. Among adult solid organ recipients, the frequency of PTLD correlates, in part, with the intensity of the immunosuppressive regimen: patients receiving renal allografts have the lowest frequency of PTLD (<1%), those with hepatic and cardiac allografts have an intermediate risk (1–2%), and those receiving heart-lung/lung or intestinal allografts have the highest frequency (5% or greater)
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Bakker NA, van Imhoff GW, Verschuuren EA, van Son WJ, Homan van der Heide JJ, Veeger NJ, Kluin PM, Kluin-Nelemans HC (2005)
Early onset post-transplant lymphoproliferative disease is associated with allograft localization.
Clin Transplant 19: 327-34




Click to access Pubmed
Caillard S, Dharnidharka V, Agodoa L, Bohen E, Abbott K (2005)
Posttransplant lymphoproliferative disorders after renal transplantation in the United States in era of modern immunosuppression.
Transplantation 80: 1233-43




Click to access Pubmed
Caillard S, Lelong C, Pessione F, Moulin B, (2006)
Post-transplant lymphoproliferative disorders occurring after renal transplantation in adults: report of 230 cases from the French Registry.
Am J Transplant 6: 2735-42




Click to access Pubmed
Opelz G, Döhler B (2004)
Lymphomas after solid organ transplantation: a collaborative transplant study report.
Am J Transplant 4: 222-30



. In children, the incidences are very much higher
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Dharnidharka VR, Tejani AH, Ho PL, Harmon WE (2002)
Post-transplant lymphoproliferative disorder in the United States: young Caucasian males are at highest risk.
Am J Transplant 2: 993-8




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Webber SA, Naftel DC, Fricker FJ, Olesnevich P, Blume ED, Addonizio L, Kirklin JK, Canter CE, (2006)
Lymphoproliferative disorders after paediatric heart transplantation: a multi-institutional study.
Lancet 367: 233-9



, with the majority of cases being associated with post-transplantation primary EBV infection
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Webber SA, Naftel DC, Fricker FJ, Olesnevich P, Blume ED, Addonizio L, Kirklin JK, Canter CE, (2006)
Lymphoproliferative disorders after paediatric heart transplantation: a multi-institutional study.
Lancet 367: 233-9



.

Peripheral blood (PB), stem cell and BM allograft recipients in general have a low risk of PTLD (~1%) with the risk of early-onset PTLD (<1 year) highest with unrelated or HLA mismatched related donors, selective T-cell depletion of donor BM, and use of antithymocyte globulin (ATG) or anti-CD3 monoclonal antibodies. The risk of PTLD in these patients increases up to 22% for those with two or more of these risk factors

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Curtis RE, Travis LB, Rowlings PA, Socié G, Kingma DW, Banks PM, Jaffe ES, Sale GE, Horowitz MM, Witherspoon RP, Shriner DA, Weisdorf DJ, Kolb HJ, Sullivan KM, Sobocinski KA, Gale RP, Hoover RN, Fraumeni JF, Deeg HJ (1999)
Risk of lymphoproliferative disorders after bone marrow transplantation: a multi-institutional study.
Blood 94: 2208-16



. An unexpectedly high incidence of EBV-associated PTLD (17%) has been recently observed in patients undergoing unrelated umbilical cord blood transplants with a non-myeloablative preparative regimen containing ATG
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Brunstein CG, Weisdorf DJ, DeFor T, Barker JN, Tolar J, van Burik JA, Wagner JE (2006)
Marked increased risk of Epstein-Barr virus-related complications with the addition of antithymocyte globulin to a nonmyeloablative conditioning prior to unrelated umbilical cord blood transplantation.
Blood 108: 2874-80



. PTLD-like lesions are rare after autologous BMT; they may be associated with additional high-dose immunosuppressive regimens and are best considered iatrogenic immunodeficiency-associated lymphoproliferative disorders rather than post-transplant LPD
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Nash RA, Dansey R, Storek J, Georges GE, Bowen JD, Holmberg LA, Kraft GH, Mayes MD, McDonagh KT, Chen CS, Dipersio J, Lemaistre CF, Pavletic S, Sullivan KM, Sunderhaus J, Furst DE, McSweeney PA (2003)
Epstein-Barr virus-associated posttransplantation lymphoproliferative disorder after high-dose immunosuppressive therapy and autologous CD34-selected hematopoietic stem cell transplantation for severe autoimmune diseases.
Biol Blood Marrow Transplant 9: 583-91



.

> Etiology
The majority of PTLD are associated with EBV infection (usually type A), and appear to represent EBV-induced monoclonal or, less often, polyclonal B-cell or monoclonal T-cell proliferations that occur in a setting of decreased T-cell immune surveillance

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Chadburn A, Chen JM, Hsu DT, Frizzera G, Cesarman E, Garrett TJ, Mears JG, Zangwill SD, Addonizio LJ, Michler RE, Knowles DM (1998)
The morphologic and molecular genetic categories of posttransplantation lymphoproliferative disorders are clinically relevant.
Cancer 82: 1978-87




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Cleary ML, Warnke R, Sklar J (1984)
Monoclonality of lymphoproliferative lesions in cardiac-transplant recipients. Clonal analysis based on immunoglobulin-gene rearrangements.
N Engl J Med 310: 477-82




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Ferry JA, Jacobson JO, Conti D, Delmonico F, Harris NL (1989)
Lymphoproliferative disorders and hematologic malignancies following organ transplantation.
Mod Pathol 2: 583-92




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Frank D, Cesarman E, Liu YF, Michler RE, Knowles DM (1995)
Posttransplantation lymphoproliferative disorders frequently contain type A and not type B Epstein-Barr virus.
Blood 85: 1396-403




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Knowles DM, Cesarman E, Chadburn A, Frizzera G, Chen J, Rose EA, Michler RE (1995)
Correlative morphologic and molecular genetic analysis demonstrates three distinct categories of posttransplantation lymphoproliferative disorders.
Blood 85: 552-65




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Nalesnik MA, Jaffe R, Starzl TE, Demetris AJ, Porter K, Burnham JA, Makowka L, Ho M, Locker J (1988)
The pathology of posttransplant lymphoproliferative disorders occurring in the setting of cyclosporine A-prednisone immunosuppression.
Am J Pathol 133: 173-92




Click to access Pubmed
Swerdlow SH (2007)
T-cell and NK-cell posttransplantation lymphoproliferative disorders.
Am J Clin Pathol 127: 887-95



. Up to 30% of PTLD are EBV-negative with some series reporting an even higher proportion of cases and with about 2/3 of T-PTLD EBV-negative
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Birkeland SA, Hamilton-Dutoit S (2003)
Is posttransplant lymphoproliferative disorder (PTLD) caused by any specific immunosuppressive drug or by the transplantation per se?
Transplantation 76: 984-8




Click to access Pubmed
Ferry JA, Jacobson JO, Conti D, Delmonico F, Harris NL (1989)
Lymphoproliferative disorders and hematologic malignancies following organ transplantation.
Mod Pathol 2: 583-92




Click to access Pubmed
Leblond V, Davi F, Charlotte F, Dorent R, Bitker MO, Sutton L, Gandjbakhch I, Binet JL, Raphael M (1998)
Posttransplant lymphoproliferative disorders not associated with Epstein-Barr virus: a distinct entity?
J Clin Oncol 16: 2052-9




Click to access Pubmed
Nelson BP, Nalesnik MA, Bahler DW, Locker J, Fung JJ, Swerdlow SH (2000)
Epstein-Barr virus-negative post-transplant lymphoproliferative disorders: a distinct entity?
Am J Surg Pathol 24: 375-85




Click to access Pubmed
Swerdlow SH (2007)
T-cell and NK-cell posttransplantation lymphoproliferative disorders.
Am J Clin Pathol 127: 887-95



. Furthermore, the proportion of EBV-negative PTLD appears to be increasing
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Nelson BP, Nalesnik MA, Bahler DW, Locker J, Fung JJ, Swerdlow SH (2000)
Epstein-Barr virus-negative post-transplant lymphoproliferative disorders: a distinct entity?
Am J Surg Pathol 24: 375-85



. EBV-negative PTLD are more common in adults, tend to occur later than EBV-positive cases and are more likely to be of monomorphic type
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Ghobrial IM, Habermann TM, Macon WR, Ristow KM, Larson TS, Walker RC, Ansell SM, Gores GJ, Stegall MD, McGregor CG (2005)
Differences between early and late posttransplant lymphoproliferative disorders in solid organ transplant patients: are they two different diseases?
Transplantation 79: 244-7




Click to access Pubmed
Nelson BP, Nalesnik MA, Bahler DW, Locker J, Fung JJ, Swerdlow SH (2000)
Epstein-Barr virus-negative post-transplant lymphoproliferative disorders: a distinct entity?
Am J Surg Pathol 24: 375-85



. Human herpesvirus 8 (HHV8)-associated PTLD are reported including post-transplant primary effusion lymphoma
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Dotti G, Fiocchi R, Motta T, Facchinetti B, Chiodini B, Borleri GM, Gavazzeni G, Barbui T, Rambaldi A (1999)
Primary effusion lymphoma after heart transplantation: a new entity associated with human herpesvirus-8.
Leukemia 13: 664-70




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Kapelushnik J, Ariad S, Benharroch D, Landau D, Moser A, Delsol G, Brousset P (2001)
Post renal transplantation human herpesvirus 8-associated lymphoproliferative disorder and Kaposi's sarcoma.
Br J Haematol 113: 425-8




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Matsushima AY, Strauchen JA, Lee G, Scigliano E, Hale EE, Weisse MT, Burstein D, Kamel O, Moore PS, Chang Y (1999)
Posttransplantation plasmacytic proliferations related to Kaposi's sarcoma-associated herpesvirus.
Am J Surg Pathol 23: 1393-400



; however, the etiology of the vast majority of EBV-negative PTLD is unknown. Some may be due to EBV that is no longer detectable
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Srinivas SK, Sample JT, Sixbey JW (1998)
Spontaneous loss of viral episomes accompanying Epstein-Barr virus reactivation in a Burkitt's lymphoma cell line.
J Infect Dis 177: 1705-9



, some due to other unknown viruses and some due to chronic antigenic stimulation, including by the transplant itself
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Birkeland SA, Hamilton-Dutoit S (2003)
Is posttransplant lymphoproliferative disorder (PTLD) caused by any specific immunosuppressive drug or by the transplantation per se?
Transplantation 76: 984-8



. The EBV-negative cases are still considered to represent PTLD and some may respond to decreased immuno­suppression
Click to access Pubmed
Nelson BP, Nalesnik MA, Bahler DW, Locker J, Fung JJ, Swerdlow SH (2000)
Epstein-Barr virus-negative post-transplant lymphoproliferative disorders: a distinct entity?
Am J Surg Pathol 24: 375-85



.

The majority (>90%) of PTLD in solid organ recipients are of host origin and only a minority of donor origin. Donor origin PTLD appear to be most common in liver and lung allograft recipients, and frequently involve the allograft

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Armes JE, Angus P, Southey MC, Battaglia SE, Ross BC, Jones RM, Venter DJ (1994)
Lymphoproliferative disease of donor origin arising in patients after orthotopic liver transplantation.
Cancer 74: 2436-41




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Chadburn A, Suciu-Foca N, Cesarman E, Reed E, Michler RE, Knowles DM (1995)
Post-transplantation lymphoproliferative disorders arising in solid organ transplant recipients are usually of recipient origin.
Am J Pathol 147: 1862-70




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Larson RS, Scott MA, McCurley TL, Vnencak-Jones CL (1996)
Microsatellite analysis of posttransplant lymphoproliferative disorders: determination of donor/recipient origin and identification of putative lymphomagenic mechanism.
Cancer Res 56: 4378-81




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Spiro IJ, Yandell DW, Li C, Saini S, Ferry J, Powelson J, Katkov WN, Cosimi AB (1993)
Brief report: lymphoma of donor origin occurring in the porta hepatis of a transplanted liver.
N Engl J Med 329: 27-9




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Weissmann DJ, Ferry JA, Harris NL, Louis DN, Delmonico F, Spiro I (1995)
Posttransplantation lymphoproliferative disorders in solid organ recipients are predominantly aggressive tumors of host origin.
Am J Clin Pathol 103: 748-55



. In contrast, the majority of PTLD in BM allograft recipients are of donor origin, as would be expected, since successful engraftment results in an immune system that is nearly exclusively of donor origin
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Zutter MM, Martin PJ, Sale GE, Shulman HM, Fisher L, Thomas ED, Durnam DM (1988)
Epstein-Barr virus lymphoproliferation after bone marrow transplantation.
Blood 72: 520-9



.

> Sites of involvement
Involvement of lymph node, gastrointestinal tract, lungs and liver are common in all allograft types, whereas central nervous system (CNS) involvement is rare

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Ferry JA, Jacobson JO, Conti D, Delmonico F, Harris NL (1989)
Lymphoproliferative disorders and hematologic malignancies following organ transplantation.
Mod Pathol 2: 583-92




Click to access Pubmed
Nalesnik MA, Jaffe R, Starzl TE, Demetris AJ, Porter K, Burnham JA, Makowka L, Ho M, Locker J (1988)
The pathology of posttransplant lymphoproliferative disorders occurring in the setting of cyclosporine A-prednisone immunosuppression.
Am J Pathol 133: 173-92




Click to access Pubmed
Penn I (1991)
The changing pattern of posttransplant malignancies.
Transplant Proc 23: 1101-3




Click to access Pubmed
Webber SA, Naftel DC, Fricker FJ, Olesnevich P, Blume ED, Addonizio L, Kirklin JK, Canter CE, (2006)
Lymphoproliferative disorders after paediatric heart transplantation: a multi-institutional study.
Lancet 367: 233-9



. The CNS may be the only site of disease or may be associated with multiorgan involvement
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Castellano-Sanchez AA, Li S, Qian J, Lagoo A, Weir E, Brat DJ (2004)
Primary central nervous system posttransplant lymphoproliferative disorders.
Am J Clin Pathol 121: 246-53



. In solid organ recipients, PTLD frequently involves the allograft and this may cause diagnostic confusion since rejection and infection may result in a similar clinical picture. Allograft involvement appears more common in early-onset, EBV-positive disease
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Bakker NA, van Imhoff GW, Verschuuren EA, van Son WJ, Homan van der Heide JJ, Veeger NJ, Kluin PM, Kluin-Nelemans HC (2005)
Early onset post-transplant lymphoproliferative disease is associated with allograft localization.
Clin Transplant 19: 327-34




Click to access Pubmed
Ghobrial IM, Habermann TM, Macon WR, Ristow KM, Larson TS, Walker RC, Ansell SM, Gores GJ, Stegall MD, McGregor CG (2005)
Differences between early and late posttransplant lymphoproliferative disorders in solid organ transplant patients: are they two different diseases?
Transplantation 79: 244-7



. The heart is the only organ in which allograft involvement is very rare. "Early lesions" often present with tonsil and/or adenoid involvement but may also occur at other sites. Overt BM involvement by polymorphic and monomorphic PTLD is not common, and PB is rarely involved. Bone marrow allograft recipients tend to present with widespread disease involving nodal and extranodal sites, including liver, spleen, gastrointestinal tract and lungs
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Penn I (1991)
The changing pattern of posttransplant malignancies.
Transplant Proc 23: 1101-3




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Shapiro RS, McClain K, Frizzera G, Gajl-Peczalska KJ, Kersey JH, Blazar BR, Arthur DC, Patton DF, Greenberg JS, Burke B (1988)
Epstein-Barr virus associated B cell lymphoproliferative disorders following bone marrow transplantation.
Blood 71: 1234-43




Click to access Pubmed
Zutter MM, Martin PJ, Sale GE, Shulman HM, Fisher L, Thomas ED, Durnam DM (1988)
Epstein-Barr virus lymphoproliferation after bone marrow transplantation.
Blood 72: 520-9



.

> Clinical features
The clinical features of PTLD are highly variable and correlate with the type of allograft, and to some extent, with the morphologically defined categories. Almost all solid organ transplant recipients are currently managed with a calcineurin inhibitor (cyclosporine or tacrolimus). With these agents, PTLD frequently presents in the first year after transplantation, earlier than tended to be observed in the ­ pre-­cyclosporine era

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Nalesnik MA, Jaffe R, Starzl TE, Demetris AJ, Porter K, Burnham JA, Makowka L, Ho M, Locker J (1988)
The pathology of posttransplant lymphoproliferative disorders occurring in the setting of cyclosporine A-prednisone immunosuppression.
Am J Pathol 133: 173-92




Click to access Pubmed
Penn I (1991)
The changing pattern of posttransplant malignancies.
Transplant Proc 23: 1101-3



. EBV-­negative PTLD and T/NK-cell PTLD tend to present later (median time to occurrence 4–5 years and 6.5 years, respectively)
Click to access Pubmed
Leblond V, Davi F, Charlotte F, Dorent R, Bitker MO, Sutton L, Gandjbakhch I, Binet JL, Raphael M (1998)
Posttransplant lymphoproliferative disorders not associated with Epstein-Barr virus: a distinct entity?
J Clin Oncol 16: 2052-9




Click to access Pubmed
Nelson BP, Nalesnik MA, Bahler DW, Locker J, Fung JJ, Swerdlow SH (2000)
Epstein-Barr virus-negative post-transplant lymphoproliferative disorders: a distinct entity?
Am J Surg Pathol 24: 375-85




Click to access Pubmed
Swerdlow SH (2007)
T-cell and NK-cell posttransplantation lymphoproliferative disorders.
Am J Clin Pathol 127: 887-95



. The majority of PTLD in BM allograft recipients develop within the first six months
Click to access Pubmed
Curtis RE, Travis LB, Rowlings PA, Socié G, Kingma DW, Banks PM, Jaffe ES, Sale GE, Horowitz MM, Witherspoon RP, Shriner DA, Weisdorf DJ, Kolb HJ, Sullivan KM, Sobocinski KA, Gale RP, Hoover RN, Fraumeni JF, Deeg HJ (1999)
Risk of lymphoproliferative disorders after bone marrow transplantation: a multi-institutional study.
Blood 94: 2208-16



. PTLD presentation may be non-specific with features such as malaise, lethargy, weight loss and fever. Lymphadenopathy and organ-­specific dysfunction are also common presentations. Obstructive symptoms such as enlarged tonsils are another type of presentation. Presentation with disseminated disease seems to be less common in the current era, perhaps due to increasing awareness of the diagnosis and due to routine EBV viral load monitoring of seronegative recipients in many transplant centres.

> Prognosis and predictive factors
The "early" lesions tend to regress with reduction in immune suppression, and if this can be accomplished without graft rejection, the prognosis is excellent, particularly in children

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Lones MA, Mishalani S, Shintaku IP, Weiss LM, Nichols WS, Said JW (1995)
Changes in tonsils and adenoids in children with posttransplant lymphoproliferative disorder: report of three cases with early involvement of Waldeyer's ring.
Hum Pathol 26: 525-30




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Zangwill SD, Hsu DT, Kichuk MR, Garvin JH, Stolar CJ, Haddad J, Stylianos S, Michler RE, Chadburn A, Knowles DM, Addonizio LJ (1998)
Incidence and outcome of primary Epstein-Barr virus infection and lymphoproliferative disease in pediatric heart transplant recipients.
J Heart Lung Transplant 17: 1161-6



. Polymorphic and less often monomorphic PTLD may also regress with reduction in immune suppression
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Starzl TE, Nalesnik MA, Porter KA, Ho M, Iwatsuki S, Griffith BP, Rosenthal JT, Hakala TR, Shaw BW, Hardesty RL (1984)
Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy.
Lancet 1: 583-7




Click to access Pubmed
Webber SA, Naftel DC, Fricker FJ, Olesnevich P, Blume ED, Addonizio L, Kirklin JK, Canter CE, (2006)
Lymphoproliferative disorders after paediatric heart transplantation: a multi-institutional study.
Lancet 367: 233-9



. However, rebound acute and chronic rejection may be observed and can lead to graft loss and death
Click to access Pubmed
Webber SA, Naftel DC, Fricker FJ, Olesnevich P, Blume ED, Addonizio L, Kirklin JK, Canter CE, (2006)
Lymphoproliferative disorders after paediatric heart transplantation: a multi-institutional study.
Lancet 367: 233-9



. A proportion of polymorphic PTLD and even more numerous monomorphic PTLD fail to regress, and require additional therapies such as monoclonal antibodies directed against B-cell antigens (most commonly anti-CD20)
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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 (2006)
Efficacy and safety of rituximab in B-cell post-transplantation lymphoproliferative disorders: results of a prospective multicenter phase 2 study.
Blood 107: 3053-7




Click to access Pubmed
Elstrom RL, Andreadis C, Aqui NA, Ahya VN, Bloom RD, Brozena SC, Olthoff KM, Schuster SJ, Nasta SD, Stadtmauer EA, Tsai DE (2006)
Treatment of PTLD with rituximab or chemotherapy.
Am J Transplant 6: 569-76



, chemotherapy
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Choquet S, Trappe R, Leblond V, Jäger U, Davi F, Oertel S (2007)
CHOP-21 for the treatment of post-transplant lymphoproliferative disorders (PTLD) following solid organ transplantation.
Haematologica 92: 273-4




Click to access Pubmed
Elstrom RL, Andreadis C, Aqui NA, Ahya VN, Bloom RD, Brozena SC, Olthoff KM, Schuster SJ, Nasta SD, Stadtmauer EA, Tsai DE (2006)
Treatment of PTLD with rituximab or chemotherapy.
Am J Transplant 6: 569-76




Click to access Pubmed
Gross TG, Bucuvalas JC, Park JR, Greiner TC, Hinrich SH, Kaufman SS, Langnas AN, McDonald RA, Ryckman FC, Shaw BW, Sudan DL, Lynch JC (2005)
Low-dose chemotherapy for Epstein-Barr virus-positive post-transplantation lymphoproliferative disease in children after solid organ transplantation.
J Clin Oncol 23: 6481-8



or combinations of both. Several centres are also performing phase I clinical trials of cellular immunotherapy to restore EBV-specific cytotoxic T-cell immunity in EBV-driven refractory disease
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Comoli P, Basso S, Zecca M, Pagliara D, Baldanti F, Bernardo ME, Barberi W, Moretta A, Labirio M, Paulli M, Furione M, Maccario R, Locatelli F (2007)
Preemptive therapy of EBV-related lymphoproliferative disease after pediatric haploidentical stem cell transplantation.
Am J Transplant 7: 1648-55




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Haque T, Wilkie GM, Jones MM, Higgins CD, Urquhart G, Wingate P, Burns D, McAulay K, Turner M, Bellamy C, Amlot PL, Kelly D, MacGilchrist A, Gandhi MK, Swerdlow AJ, Crawford DH (2007)
Allogeneic cytotoxic T-cell therapy for EBV-positive posttransplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial.
Blood 110: 1123-31




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Savoldo B, Goss JA, Hammer MM, Zhang L, Lopez T, Gee AP, Lin YF, Quiros-Tejeira RE, Reinke P, Schubert S, Gottschalk S, Finegold MJ, Brenner MK, Rooney CM, Heslop HE (2006)
Treatment of solid organ transplant recipients with autologous Epstein Barr virus-specific cytotoxic T lymphocytes (CTLs).
Blood 108: 2942-9



. The myelomatous lesions usually do not regress with decreased immunosuppression, and T/NK-cell PTLD are also considered to be aggressive with the exception of those of large granular lymphocyte type
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Swerdlow SH (2007)
T-cell and NK-cell posttransplantation lymphoproliferative disorders.
Am J Clin Pathol 127: 887-95



. Nevertheless, some T-PTLD do respond to reconstitution of the patients’ immune system. The plasmacytoma-like lesions have a variable outcome
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Joseph G, Barker RL, Yuan B, Martin A, Medeiros J, Peiper SC (1994)
Posttransplantation plasma cell dyscrasias.
Cancer 74: 1959-64



. EBV negativity in PTLD and even among the T/NK-cell PTLD, is also considered an adverse prognostic indicator, although not all studies document a survival difference
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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 (2006)
Efficacy and safety of rituximab in B-cell post-transplantation lymphoproliferative disorders: results of a prospective multicenter phase 2 study.
Blood 107: 3053-7




Click to access Pubmed
Swerdlow SH (2007)
T-cell and NK-cell posttransplantation lymphoproliferative disorders.
Am J Clin Pathol 127: 887-95



.

A number of additional prognostic factors associated with an adverse outcome include multiple sites of disease and advanced stage, older age at diagnosis, late onset disease, high International Prognostic Index and elevated lactate dehydrogenase

Click to access Pubmed
Caillard S, Lelong C, Pessione F, Moulin B, (2006)
Post-transplant lymphoproliferative disorders occurring after renal transplantation in adults: report of 230 cases from the French Registry.
Am J Transplant 6: 2735-42




Click to access Pubmed
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 (2006)
Efficacy and safety of rituximab in B-cell post-transplantation lymphoproliferative disorders: results of a prospective multicenter phase 2 study.
Blood 107: 3053-7




Click to access Pubmed
Elstrom RL, Andreadis C, Aqui NA, Ahya VN, Bloom RD, Brozena SC, Olthoff KM, Schuster SJ, Nasta SD, Stadtmauer EA, Tsai DE (2006)
Treatment of PTLD with rituximab or chemotherapy.
Am J Transplant 6: 569-76




Click to access Pubmed
Ghobrial IM, Habermann TM, Maurer MJ, Geyer SM, Ristow KM, Larson TS, Walker RC, Ansell SM, Macon WR, Gores GG, Stegall MD, McGregor CG (2005)
Prognostic analysis for survival in adult solid organ transplant recipients with post-transplantation lymphoproliferative disorders.
J Clin Oncol 23: 7574-82




Click to access Pubmed
Trofe J, Buell JF, Beebe TM, Hanaway MJ, First MR, Alloway RR, Gross TG, Succop P, Woodle ES (2005)
Analysis of factors that influence survival with post-transplant lymphoproliferative disorder in renal transplant recipients: the Israel Penn International Transplant Tumor Registry experience.
Am J Transplant 5: 775-80



. However, risk factors for adverse outcome vary greatly between studies. Multi-site disease may not be a risk factor for adverse outcome in paediatric patients
Click to access Pubmed
Webber SA, Naftel DC, Fricker FJ, Olesnevich P, Blume ED, Addonizio L, Kirklin JK, Canter CE, (2006)
Lymphoproliferative disorders after paediatric heart transplantation: a multi-institutional study.
Lancet 367: 233-9



. Overall, the mortality of PTLD is greater in BM allograft recipients than solid organ allograft recipients and may be lower in children than adults.







Steven H. Swerdlow
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Steven H. Swerdlow
Department of Pathology, Division of Hematopathology
UPMC Presbyterian
Pittsburgh
USA




Steven A. Webber
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Steven A. Webber







Amy Chadburn
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Amy Chadburn
Department of Pathology and Laboratory Medicine
Weill Cornell Medical College
New York





Judith Ann Ferry
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Judith Ann Ferry
Department of Pathology, Warren 2
Massachusetts General Hospital
Boston
USA