Use of rituximab and irradiated donor-derived lymphocytes to control Epstein–Barr virus-associated lymphoproliferation in patients undergoing related haplo-identical stem cell transplantation

Abstract

Summary:Epstein-Barr virus-associated lymphoproliferative disorder (EBV-LPD) is an uncommon but potentially fatal complication of allogeneic stem cell transplantation. We report here two patients who underwent T cell-depleted mismatched-related stem cell transplantation for hematologic malignancies and required aggressive post-transplant immunosuppression for graft-versus host disease (GVHD). Both patients subsequently developed markedly elevated EBV-DNA titers in association with monoclonal, light chain-restricted B cell populations in the blood. Although immunosuppressive medications were rapidly tapered, neither patient could receive potentially curative therapy with unmanipulated donorderived lymphocyte infusions (DLI) because of the substantial risk of severe GVHD. Therefore, both patients received repeated courses of rituximab, an anti-CD20 monoclonal antibody, in combination with irradiated DLI. This therapeutic strategy resulted in normalization of the elevated EBV-DNA titers and disappearance of the monoclonal B cell populations. Our results suggest that rituximab and possibly irradiated DLI played an important role in controlling early EBV-LPD in these two patients and may be an effective alternative therapeutic strategy for patients who develop EBV-LPD post transplant and are unable to receive unmanipulated DLI. Keywords: HLA nonidentical; donor lymphocyte infusion; haploidentical; EBV; lymphoproliferative disease Epstein-Barr virus-associated lymphoproliferation (EBV-LPD) which occurs early after allogeneic transplant is frequently characterized by a fulminant clinical course and a poor response to antiviral and antineoplastic treatment. [1][2][3][4] Infusion of unmanipulated donor leukocytes (DLI) 5 and, more recently, in vitro generated donor-derived virus-

Rituximab for steroid-refractory chronic graft-versus-host disease

“…23,26 Rituximab has also been used as therapy for EBV reactivation and posttransplantation lymphoproliferative disease. [27][28][29][30][31][32][33][34] In our study, responses were noted in patients with cutaneous and musculoskeletal disease, a finding that has previously been reported. 14,16,17 Although it is possible that other involved organs (such as the eyes and oral mucosa) did not respond because of the destruction of target tissues (such as the lacrimal and salivary glands), or because our clinical measurement tools were inadequate to detect improvement, it is notable that rituximab is now being used successfully in autoimmune conditions resembling cutaneous and musculoskeletal chronic GVHD.…”

Epstein–Barr virus-associated B cell lymphoproliferative disorder following mismatched related T cell-depleted bone marrow transplantation

“…25,26 We have used Rituxan as part of the initial treatment in two patients with one showing a partial response. With such a small number of patients, It is impossible to draw any meaningful conclusion.…”

The history and future of T-cell depletion as graft-versus-host disease prophylaxis for allogeneic hematopoietic stem cell transplantation

“…[183][184][185][186] For patients who are not candidates for DLI or EBV-specific CTL therapy, recent small case series have reported promising responses with the use of the anti-CD20 monoclonal antibody rituximab. 187,188 Rituximab is relatively safe and may prove to be as effective as DLI in the treatment of EBV-LPD. Polymerase chain reaction methods to detect EBV DNA may be an effective means of diagnosing patients with EBV-LPDs prior to the onset of clinically evident disease.…”