Use of Rituximab As a Pre-Emptive Therapy for Epstein-Barr Virus (EBV)-Associated Lymphoproliferative Disorders in 86 Adult Patients Having Allogeneic Stem Cell Transplantation

Allogeneic stem cell transplantation may induce Epstein Barr Virus (EBV) reactivation. Some risk factors were identified. Despite the lack of guideline for treatment in such a situation, rituximab is commonly used.

e: To assess the efficiency and tolerance of rituximab, we have conducted a retrospective study between 2005 and 2009 in the unit of transplantation. All the patients having allogenic transplantation with a viral load >500 copy/ml and receiving rituximab (375mg/m²/week) until negative viral load were included in this study. Earlier EBV reactivation was defined by occuring within 1 year after allogeneic transplantation.

86 patients had EBV-reactivation treated by rituximab. Median age was 49.5 years (39–58). Eighteen (21%) patients had a chronic B-cell malignancy. Thirty (35%) patients received myeloablative regimen, 56 (65%) had reduced intensity conditioning regimen. Graft were peripheral blood stem cells for 66 (77%) patients, bone marrow for 10 (11.5%) and cord blood for 10 (11.5%) patients. Forty-seven (68%) EBV-reactivations occurred with unrelated donor transplantation (MUD), and 30 (33.4%) concerned mismatched allografts. Twenty (23%) patients received anti-thymoglobulin (ATG), 38 (44%) received Fludarabine and 10 (12%) both. 30 (35%) patients reactivated another herpes virus in the same time. Seventy (82%) patients were in complete response or in very good partial response at the time of the reactivation.

Most of the reactivations occurred before 1 year (90%, n=77) with a median day at D165 (5–1531). In 76 (88%) cases, couple recipient-donor had a positive EBV serology before allogenic transplantation and in 7 cases (8%), only the recipient was positive.

The rate of complete response after rituximab was 82.5% (n=66). Relapse rate after the end of treatment was 45%. Two patients developed a post-transplant lymphoma disorder despite preemptive treatment. Use of ATG (OR 14.3 (4–51), EBV negative recipient serology (OR=7.5 (1.7-33.5), acute haematological malignancy or myelodysplastic syndrome versus chronic B-cell malignancies (OR 7 (2.1–22), and previous autologous transplantation (OR 14.7 (4.7-46.4) were poor prognosis factor for response to rituximab. The type of the disease, the type of the donor, the conditioning regimen, the type of match and chimerism, the use of ATG did not influence the time to response. Rituximab decreased the rate and the severity of acute Graft versus Host Disease (GvHD) (p<0.01). Rituximab did not modify CD4 and CD8 lymphocyte counts. NK cell number increased, starting at 6 months after the end of treatment, and B-lymphocytes from 6 months. Median overall survival (OS) was not reached at 2 years. There is a trend for a better survival in later EBV-reactivation than the earlier (p=0.08) one. In MUD allograft, EBV reactivation occurred statistically later than with sibling donor allograft (p=0.013).

Rituximab is an efficient and safe pre-emptive therapy for EBV reactivation. Furthermore, the use of rituximab for EBV reactivation may support a positive effect for acute GvHD.

No relevant conflicts of interest to declare.