Pre-Emptive Use of Rituximab in Epstein–Barr Virus Reactivation: Incidence, Predictive Factors, Monitoring, and Outcomes

Abstract

Post-transplant lymphoproliferative disease (PTLD) is a fatal complication of hematopoietic cell transplantation (HCT) associated with the Epstein–Barr virus (EBV). Multiple factors such as transplant type, graft-versus-host disease (GVHD), human leukocyte antigens (HLA) mismatch, patient age, and T-lymphocyte-depleting treatments increase the risk of PTLD. EBV reactivation in hematopoietic cell transplant recipients is monitored through periodic quantitative polymerase chain reaction (Q-PCR) tests. However, substantial uncertainty persists regarding the clinically significant EBV levels for these patients. Guidelines recommend initiating EBV monitoring no later than four weeks post-HCT and conducting it weekly. Pre-emptive therapies, such as the reduction of immunosuppressive therapy and the administration of rituximab to treat EBV viral loads are also suggested. In this study, we investigated the occurrence of EBV-PTLD in 546 HCT recipients, focusing on the clinical manifestations and risk factors associated with the disease. We managed to identify 67,150 viral genomic copies/mL as the cutoff point for predicting PTLD, with 80% sensitivity and specificity. Among our cohort, only 1% of the patients presented PTLD. Anti-thymocyte globulin (ATG) and GVHD were independently associated with lower survival rates and higher treatment-related mortality. According to our findings, prophylactic measures including regular monitoring, pre-emptive therapy, and supportive treatment against infections can be effective in preventing EBV-related complications. This study also recommends conducting EBV monitoring at regular intervals, initiating pre-emptive therapy when viral load increases, and identifying factors that increase the risk of PTLD. Our study stresses the importance of frequent and careful follow-ups of post-transplant complications and early intervention in order to improve survival rates and reduce mortality.

Genetics and Epigenetics in Acquired Hemophilia A: From Bench to Bedside

“…Furthermore, de novo anti-rpFVIII inhibitors can be developed in these patients, leading to discontinuation of the treatment [100,101]. Treatment response to hemostatic agents should be evaluated clinically, and a treatment switch might be implemented if the chosen hemostatic agent is found to be ineffective [102]. Initial treatment with human FVIII should be limited only to cases when access to the above three agents is not available and in patients with low-titer inhibitors (<5 BU) [87].…”

“…In a recently published retrospective study, 80 participants who received corticosteroids combined with rituximab IST had a 93.3% complete remission rate [ 101 ]. Rituximab has been used as an immunosuppressant in various benign and malignant hematological disorders [ 102 , 103 , 104 ] as cytotoxic agents’ cyclophosphamide (PO, 1.5–2 mg/kg/day, for a maximum of 6 weeks) or mycophenolate mofetil (1 g/day for 1 week, and after 2 g/day). In a randomized controlled study comparing corticosteroids plus rituximab with corticosteroids plus cyclophosphamide in patients with AHA, similar efficacy and safety were reported between the two drug combinations [ 105 ].…”