Successful preemptive therapy with single‐dose rituximab for Epstein‐Barr virus infection to prevent post‐transplant lymphoproliferative disease after pediatric hematopoietic stem cell transplantation

Abstract

oproliferative disease occurs in 1%-3.5% of pediatric patients after undergoing hematopoietic stem cell transplantation (HSCT). 1,2 B cell-related PTLD accounts for a major portion of all PTLD cases, and only 5% of cases are of natural killer T cell or Hodgkin disease origin. 3 The risk factors of PTLD include infection, degree and level of immunosuppressive therapy, genetic susceptibility, and HSCT-related factors. Of them, 50%-70% of all PTLD cases are associated with Epstein-Barr virus (EBV) infection. 3 Uncontrolled EBV-driven B cell proliferation extends the half-life of virally infected cells and leads to malignant transformation. 4 Known prophylaxis and treatments of EBV-related PTLD include the administration of rituximab (CD20 monoclonal antibodies), reduction of immunosuppression, Abstract Background: The efficacy of preemptive treatment containing rituximab to prevent post-transplant lymphoproliferative disease (PTLD) in children has not yet been fully elucidated. Methods:We analyzed 19 pediatric patients who developed high Epstein-Barr virus (EBV) DNAemia (EBV viral load of greater than 40 000 copies/mL) after allogeneic hematopoietic stem cell transplantation (HSCT) and were preemptively administered rituximab. Rituximab was intravenously injected at a dose of 375 mg/m 2 once the EBV viral load was greater than 40 000 copies/mL. Results:In all 19 patients, EBV DNAemia was eradicated after a median of 9 days (range, 3-20 days), and PTLD did not occur. One patient had transient fever, and four patients did not fully recover B cell counts after transplantation. We suggested that delayed B cell recovery was caused by chronic graft-versus-host disease (GVHD) related drugs, not rituximab administration. And there were no other infection-related side effects. Conclusions:In conclusion, preemptive therapy containing rituximab is expected to reduce the incidence of PTLD after HSCT and improve post-transplantation outcomes in children. K E Y W O R D SEpstein-Barr virus, hematopoietic stem cell transplantation, post-transplant lymphoproliferative disease, rituximab

Epstein–Barr Virus Monitoring after an Allogeneic Hematopoietic Stem Cell Transplant: Review of the Recent Data and Current Practices in Canada

“…In the single largest cohort of adult patients reported to date (n = 107 treated patients), EBV clearance was achieved in 95% [56]. In pediatric patients, the efficacy of pre-emptive strategies for EBV clearance was similar, ranging from 89% [57] (HID transplant) to 100% [58]. These studies all conclude that pre-emptive therapy of EBV reactivation post-HSCT is efficient in the control of EBV reactivation and may effectively prevent PTLD.…”

“…When plasma is used, the threshold of 1000 copies/mL (defined as persistent or on two consecutive occasions) was mostly used [17,34,62] or the corresponding 1000 copies/10 6 in PBMCs [57]. When WB is used, this value can range from 40,000 copies/mL [4,58], knowing that EBV load in WB is considered as 10-to 100-fold higher than in plasma samples [63]. Stocker et al proposed a threshold from 5000 IU/mL in WB, whereas Lindsay et al treated patient with 1000 to 100,000 IU/mL in plasma.…”

Monoclonal antibodies used for management of hematological disorders

“…It has also been used to prevent post stem cell transplantation Epstein-Barr virus disease in pediatric patients. [11] Quite a few allergic, infectious and non-infectious side effects have been recorded. Side effects and complications in using this antibody has been extensively reviewed.…”

Reactivation of cytomegalovirus, human herpes virus, and Epstein-Barr virus infections after hemapoietic stem cell transplantation in children

“…[6][7][8]. Кроме того, реактивация вируса Эпштейна -Барр (ВЭБ) ассоциирована с развитием специ фического осложнения -лимфопролиферативного заболевания после трансплантации от аллогенного донора (алло-ТГСК) [9,10,11], что также требует контроля уровня виремии и прове-дения терапии с целью профилактики даже в отсутствие клинической манифестации инфекции.…”