**2. PTLD in SOT vs. HSCT**

Compared to the general population, the SOT patients have a 30–60-fold increased risk of developing PTLD. Most cases of PTLD occur within the first year after transplantation. EBV DNAemia occurs after transplantation in significantly more SOT recipients than HSCT patients. Correspondingly, more SOT patients also develop PTLD than HSCT patients and also significantly later posttransplant compared to HSCT recipients. The median length of time between transplant and diagnosis of PTLD for SOT patients is 2.8 years versus 121 days for HSCT patients [1, 4].

#### **2.1. PTLD in SOT**

**1. Introduction**

lesions and a worse prognosis [1].

presenting as aggressive non-Hodgkin lymphoma.

396 Organ Donation and Transplantation - Current Status and Future Challenges

transplant setting and are considered a bona fide PTLD [29, 30].

**2. PTLD in SOT vs. HSCT**

PTLD is an uncommon complication of hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) with a broad clinical and pathological spectrum ranging from an acute, self-limited illness resembling infectious mononucleosis with histologically innocuous polyclonal lymphoid proliferation to aggressive, life-threatening tumors resembling aggressive lymphomas in immunocompetent individuals. The overall incidence of PTLD is about 1–5% in solid organ transplant (SOT) recipients and 1% in hematopoietic stem cell transplant (HSCT) recipients. Most cases of PTLD occur within the first year after transplantation. Lateonset PTLD, occurring years after transplantation, is often associated with more monoclonal

The clinical outcome of untreated aggressive PTLD after HSCT is very poor, suggestive of the biologic heterogeneity between the PTLD and de novo DLBCL. The mortality associated with PTLD induced by EBV infection can be reduced by monitoring EBV by polymerase chain reaction and by preemptively giving rituximab. The prompt initiation of preemptive therapy

There is no consensus opinion as to whether a particular subtype of HSCT is associated with increased incidence of PTLD and whether salvage therapy provides survival benefits in patients developing early compared to late PTLD though, empirically, regimens that would reduce EBV-specific T cells, e.g. in vitro or in vivo T-cell purging, are believed to increase the risk of EBV-associated PTLD. Clinical features that independently predict rates of response, progression-free survival, and overall survival have not been systematically studied for PTLD

From a pathological standpoint, PTLD that represents a spectrum of lymphoid proliferations can be classified as nondestructive, polymorphic, monomorphic, and classical Hodgkin lymphoma types [29] based on morphology, immunophenotype, and clonality. Monomorphic and classical Hodgkin PTLDs are then classified based on their resemblance to de novo in lymphomas in immunocompetent individuals, e.g., diffuse large B-cell lymphoma, Burkitt lymphoma, plasmacytoma, plasma myeloma, peripheral T-cell lymphoma, NOS, hepatosplenic T-cell lymphoma, etc. The majority of monomorphic PTLDs resemble aggressive non-Hodgkin lymphoma, and most indolent lymphomas such as low-grade follicular lymphoma and EBV-negative extranodal marginal zone (MALT) lymphoma are not considered PTLD. However, a small number of EBV+ MALT lymphomas have been reported in the post-

Compared to the general population, the SOT patients have a 30–60-fold increased risk of developing PTLD. Most cases of PTLD occur within the first year after transplantation. EBV DNAemia occurs after transplantation in significantly more SOT recipients than HSCT

and early diagnosis of EBV disease are associated with decreased mortality [2, 3].

In adults, incidence rates range 1–3% in kidney and liver transplants, 1–6% in cardiac transplants, 2–6% in combined heart-lung transplants, 4–10% in lung transplants, and up to 20% in small intestine transplants. The variation in rates among the types of organs transplanted is likely related to the degree and duration of immunosuppression as well as the number of EBV-positive donor lymphocytes in the graft. PTLD is more common in lung and small bowel transplants. Duration of the posttransplant period is important because PTLD is most likely to develop in the first year following transplantation, with an incidence of 224 per 100,000 but falls to 54 per 100,000 in the second year and 31 per 100,000 in the sixth year. PTLD represents a heterogeneous group of non-Hodgkin lymphomas that vary clinically and are ill-defined morphologically [5–8].
