Management of Epstein-Barr virus-related post-transplant lymphoproliferative disorder after allogeneic hematopoietic stem cell transplantation

Abstract

Epstein-Barr virus-related post-transplant lymphoproliferative disorder (EBV-PTLD) is a rare but life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). T-cell immunodeficiency after transplantation and EBV primary infection/reactivation play major roles in the pathogenesis. Unspecific clinical manifestations make the diagnosis difficult and time consuming. Moreover, this fatal disease usually progresses rapidly, and leads to multiple organ dysfunction or death if not treated promptly. Early diagnosis of EBV-DNAemia or EBV-PTLD generally increases the chances of successful treatment by focusing on regular monitoring of EBV-DNA and detection of symptomatic patients as early as possible. Rituximab ± reduction of immunosuppression (RI) is currently the first-line choice in preemptive intervention and targeted treatment. Unless patients are suffering from severe graft versus host disease (GvHD), it is better to combine rituximab with RI. Once a probable diagnosis is made, the first-line treatment should be initiated rapidly, along with, or ahead of, biopsy, although histopathologic confirmation is requisite. In addition, EBV-specific cytotoxic T lymphocytes (EBV-CTLs) or donor lymphocyte infusion (DLI) has shown promise in cases of suboptimal response. Chemotherapy ± rituximab might lend more opportunities to refractory/relapsed patients, who might also benefit from ongoing clinical trials. Herein, we discuss our clinical experience in detail based on the current literature and our five cases.

Keywords: Epstein–Barr virus; allogeneic hematopoietic stem cell transplantation; management; post-transplant lymphoproliferative disorder.

Figure 1.

¹⁸F-FDG–PET/CT images (maximum-intensity projection). Baseline images showed extranodal lesions in the liver (SUVmax, 17.6) and the spleen (SUVmax, 19.6) (left, arrows); ¹⁸F-FDG–PET/CT after three cycles of R-COP and four doses of EBV-CTLs showed limited residual hypermetabolic lesions in the liver (SUVmax, 3.7) and the spleen (SUVmax, 3.4) (right, arrows). ¹⁸F, radionuclide fluorine 18; FDG, fluorodeoxyglucose; PET, positron emission tomography; CT, computed tomography; R, rituximab; COP, regimen including cyclophosphamide, vincristine and prednisone; EBV-CTLs, Epstein–Barr virus specific cytotoxic T lymphocytes; SUVmax, standard uptake value maximum.

Figure 2.

MRI images. Baseline images showed symmetrical, extensive, supra- and infra-tentorium lesions (left); after three doses of intrathecal rituximab, MRI showed a completely normal image (right). MRI, magnetic resonance imaging.

Figure 3.

(a) Risk factors for EBV-PTLD after HSCT listed in ECIL-6 guidelines. Recipients are defined as a high-risk group for EBV-PTLD if they undergo MFD allo-HSCT with at least one risk factor or alternative-donor HSCT, including MUD/MMUD allo-HSCT and CBT.(b) Proposed management algorithm for high-risk recipients of allo-HSCT. CBT, cord blood transplantation; CHOP, regimen including cyclophosphamide, doxorubicin, vincristine and prednisone; COP, regimen including cyclophosphamide, vincristine and prednisone; DLI, donor lymphocyte infusion; EBV-CTLs, Epstein–Barr virus-specific cytotoxic T lymphocytes; EBV-PTLD, Epstein–Barr virus-related post-transplant lymphoproliferative disorder; ECIL-6, the sixth edition guideline published by the European Conference on Infections in Leukaemia; FU, follow-up; GvHD, graft-versus-host disease; HLA, human leukocyte antigen; haplo-PTCy-HSCT, haploidentical hematopoietic stem cell transplantation incorporating post-transplant cyclophosphamide; HSCT, hematopoietic stem cell transplantation; MFD, matched family donor; MMUD, mismatched unrelated donor; MUD, matched unrelated donor; MSC, mesenchymal stem cell; RI, reduction of immunosuppression; Tx, transplantation.