Hematopoietic Stem Cell Transplantation for the Treatment of Epstein-Barr Virus-Associated T- or NK-Cell Lymphoproliferative Diseases and Associated Disorders

Abstract

Chronic active Epstein-Barr virus infection (CAEBV) is a prototype of EBV-associated T- and/or NK-cell (EBV+ T/NK-cell) lymphoproliferative disorders. Most subtypes of these are lethal. We established a unified treatment strategy composed of step 1 (immunochemotherapy: steroids, cyclosporine A, and etoposide), step 2 (multi-drug block chemotherapy), and step 3 (allogeneic hematopoietic stem cell transplantation; HSCT) for CAEBV and its related diseases. Allogeneic HSCT is the only cure for CAEBV with few exceptions. Primary-EBV infection-associated hemophagocytic lymphohistiocytosis (primary-EBV HLH) is also an EBV+ T/NK-cell lymphoproliferation. The nature of EBV+ T/NK cells in CAEBV and those in primary-EBV HLH differ. In primary-EBV HLH, most patients need step 1 only and some require step 2 for the successful induction of apoptosis in EBV-infected T cells; however, some exceptional patients require HSCT. We herein present our single institutional experience of CAEBV and primary-EBV HLH, together with that of post-transplant EBV+ T/NK-cell lymphoproliferative disease. We also discuss some practical points on HCST with a review of the literature.

Primary immune regulatory disorders for the pediatric hematologist and oncologist: A case‐based review

“…Treatment approaches have included immunomodulatory therapy, antivirals, replication inhibitors, and chemotherapy. Although these can control viral burden and tissue damage, only allogeneic transplant (from an EBV + donor) is considered curative …”

“…Three of these five received cytotoxic T‐cell therapies directed toward EBV post HSCT. Similarly, the existing literature describing outcomes of HSCT for this population documents an overall survival of approximately 70% . The optimal approach to decrease EBV burden in these patients prior to transplantation, as well as how to optimally condition for transplant, is currently unknown.…”

Incorporation of thiotepa in a reduced intensity conditioning regimen may improve engraftment after transplant for HLH

“…The third patient had underlying CAEBV and developed Grade IV GVHD six months post‐transplant and died from complications of intensive immunosuppression. Of note, all three patients that died had HLH associated with conditions that have been associated with poor outcomes after HSCT, namely STAT3 GOF, systemic JIA and CAEBV (Snowden et al , ; Snowden et al , ; Sawada & Inoue, ; Fabre et al , ).…”

Fatal Epstein‐Barr virus‐associated hemophagocytic lymphohistiocytosis with virus‐infected T cells after pediatric multivisceral transplantation: A proof‐of‐concept case report

“…However, either HSCT or emapalumab, the anti-IFN-γ monoclonal antibody, could be considered for future cases as a treatment for refractory EBV-HLH once the accurate diagnosis is made. [18][19][20] In conclusion, this case may represent several aspects of the patho-…”