**8.1. ATG and PTLD**

calcineurin inhibitors. Furthermore, recent data has contributed to and, in some instances, shed light on previous debate concerning the role of viruses other than EBV and the level of HLA mismatch as risk factors for PTLD [15]. Gene association studies focusing on key cytokines and their receptors have identified several polymorphisms that may prove useful to identify patients at risk, with distinction for early nondestructive and late occurring

The term PTLD represents a spectrum of B-cell hyperproliferative states that can be classified as nondestructive PTLD, polymorphic PTLD, monomorphic PTLD, and classical Hodgkin

Nondestructive lesions are classified as reactive plasmacytic hyperplasia, florid follicular hyperplasia, and infectious mononucleosis-like PTLD. These lesions are frequently associated with an acute illness similar to mononucleosis, with polyclonal B-cell proliferation, but without evidence of malignant transformation by definition, the lymphoid architecture is preserved.

Polymorphic PTLDs are polyclonal or monoclonal lymphoid infiltrates with evidence of destructive growth patterns including necrosis, destruction of underlying lymphoid architecture, and nuclear atypia. However, polymorphic PTLD does not otherwise meet all criteria for

Monomorphic PTLDs are monoclonal lymphoid proliferations. Monomorphic PTLD most commonly resembles aggressive B-cell lymphomas such as Burkitt lymphoma/high-grade B-cell lymphoma or diffuse large B-cell lymphoma (DLBCL), as seen in immunocompetent patients. Likewise, classical Hodgkin-like lymphoma variably resembles those observed in immunocompetent patients. Small B-cell lymphomas such as follicular lymphoma, small lymphocytic lymphoma, and EBV-negative marginal zone lymphomas that occur in the posttransplant setting are not characterized as PTLD. A small group of EBV+ MALT lymphoma is

PTLD occurs more commonly in pediatric patients than in adults. The higher incidence in children is thought to result from being EBV-naïve recipients. PTLDs can arise during posttransplant period after both myeloablative and nonmyeloablative allogeneic hematopoietic cell transplantation. EBV is frequently expressed in PTLD in patients with both HSCT and SOT. Posttransplant lymphoproliferative disorder (PTLD) has been associated with high mortality, but recent anecdotal survival appears better. NAPRTCS registry had 235 registered PTLD cases from 1988 to 2010 which showed that survival has improved with more recent

B-cell or T-/NK-cell lymphomas as characterized in immunocompetent patients [1].

monomorphic PTLD.

**6. Monomorphic PTLD vs. polymorphic PTLD**

400 Organ Donation and Transplantation - Current Status and Future Challenges

now recognized as *bona fide* PTLD [30].

PTLDs in children following kidney transplants [6, 18].

**7. Pediatric PTLD**

lymphoma, all of which may be associated with Epstein–Barr virus (EBV).

In vivo T-cell depletion (TCD) with antithymocyte globulin (ATG) or alemtuzumab (AL) is commonly used in HSCT. TCD facilitates engraftment and reduces the incidence and severity of graft-versus-host disease (GvHD). As reduced intensity conditioning (RIC) and matched unrelated donor transplants (MUD) are now being performed more frequently, ATG and AL have become integral components of preparative regimens. Although ATG and AL provide safer T-cell depletion, delayed T-cell reconstitution following TCD accounts for infectious complications and increased mortality.

EBV PTLD is predominantly derived from donor B cells before reconstitution of the EBVspecific cytotoxic T lymphocyte (CTL) response. It can, however, occur later in the most severely immunocompromised patients with additional risk factors such as donor and recipient mismatch, graft manipulation with T-cell depletion, as well as the degree and duration of immunosuppression.

In a study by Buyck et al., an overall incidence of 6.3% for EBV PTLD was reported in 89 patients with severe aplastic anemia. A marked increase in the incidence (13.3%) was noted in patients exposed to ATG, with 5 of 43 patients developing EBV PTLD [19].
