Reply to Fernández-Ruiz et al.

Abstract

We totally agree with Fernández-Ruiz et al. about the possible intrinsic role of Epstein-Barr virus (EBV) on immune response. The fact that the EBV reactivates within these patients is proof of an EBV-specific immune defect, as per definition. Nevertheless, we have observed that these patients treated with rituximab display long-lasting hypogammaglobulinemia and more risk of bacterial infection compared with a matched population. The matching was based on well-known risk factors for EBV reactivation after allogeneic hematopoietic stem-cell transplantation (HSCT). Hypogammaglobulinemia and memory B cell defect, which have been implicated in the risk of late bacterial infection (1), may be one, but not the sole, explanation for the increased risk of bacterial infections. Fernández-Ruiz et al. suggest that EBV DNAemia is a surrogate of immune defects in the organ-transplanted population. In the setting of HSCT patients, two populations can be distinguished: patients able to develop a T-specific response and to clear the virus without treatment and patients unable to develop a T-specific response and whose virus then evolved toward a lymphoproliferative disease, usually fatal without treatment (2). The preemptive treatment of EBV reactivation with rituximab has dramatically decreased posttransplant lymphoproliferative disorder incidence and posttransplant lymphoproliferative disorder–related mortality (<5%). The main message of our study is to think about the indication of a rituximab treatment on a case-per-case basis to avoid treating patients who may achieve a spontaneous clearance of EBV (stable or low EBV DNAemia) and to carefully and prospectively monitor immune reconstitution in patients treated with rituximab. The policy at our center is to only substitute patients with severe hypogammaglobulinemia (<3 gr/L) who have a history of at least one severe bacterial infection. Although prophylactic immunoglobulin substitution after HSCT has not shown any benefit in a randomized prospective study (3), a study based on immunoglobulin substitution after rituximab treatment could still be conducted. Marie Robin Régis de Latour Aliénor Xhaard Gérard Socié Service d’Hématologie Greffe Assistance Publique Hpitaux de Paris Hôpital Saint-Louis Paris, France