Management of PTLD After Hematopoietic Stem Cell Transplantation: Immunological Perspectives

Abstract

Post-transplant lymphoproliferative disorders (PTLDs) are life-threatening complications of iatrogenic immune impairment after allogeneic hematopoietic stem cell transplantation (HSCT). In the pediatric setting, the majority of PTLDs are related to the Epstein-Barr virus (EBV) infection, and present as B-cell lymphoproliferations. Although considered rare events, PTLDs have been increasingly observed with the widening application of HSCT from alternative sources, including cord blood and HLA-haploidentical stem cell grafts, and the use of novel agents for the prevention and treatment of rejection and graft-vs.-host disease. The higher frequency initially paralleled a poor outcome, due to limited therapeutic options, and scarcity of controlled trials in a rare disease context. In the last 2 decades, insight into the relationship between EBV and the immune system, and advances in early diagnosis, monitoring and treatment have changed the approach to the management of PTLDs after HSCT, and significantly ameliorated the prognosis. In this review, we summarize literature on the impact of combined viro-immunologic assessment on PTLD management, describe the various strategies for PTLD prevention and preemptive/curative treatment, and discuss the potential of novel immune-based therapies in the containment of this malignant complication.

Adoptive T‐cell therapy targeting Epstein–Barr virus as a treatment for multiple sclerosis

“…The latency III profile is associated with lymphoproliferative diseases that arise in immunocompromised patients, whereas the latency I and II profiles are present in cancers that arise in patients that are otherwise immunocompetent 10,12,13 . These observations demonstrate that immune pressure plays a key role in regulating the survival of EBV‐transformed cells 14,15 …”

“…10,12,13 These observations demonstrate that immune pressure plays a key role in regulating the survival of EBV-transformed cells. 14,15 During primary lytic stages of infection, EBV uses many distinct proteins to prevent its clearance by the immune system. 16 These proteins primarily act through the suppression of antigen processing and presentation via the MHC pathways and the regulation of cytokine expression, thus restricting T-cell-mediated clearance of lytically infected cells.…”

“… 10 , 12 , 13 These observations demonstrate that immune pressure plays a key role in regulating the survival of EBV‐transformed cells. 14 , 15 …”

Haploidentical hematopoietic cell transplant recipient presents with late‐onset Epstein Barr virus‐associated posttransplant lymphoproliferative disorder

“…EBV is implicated in the development of PTLD, and non-EBVassociated posttransplant lymphoproliferative disorders in transplant are not considered PTLD per european conference on infections in leukemia (ECIL) guidelines [7,8]. Early posttransplant, routine serologic studies of EBV DNA are recommended and expected to be noticed within the first 4 months, if present.…”

Recent Advances in Adult Post-Transplant Lymphoproliferative Disorder

“…Alternatively, if inadequate response to rituximab monotherapy is noted, consolidation R-CHOP can be used. Prospective or observational large population studies are not available for this rare entity; therefore, decision making is largely institution-dependent [ 101 ].…”