Efficacy of early single low dose of rituximab in prophylaxis of EBV reactivation and EBV related post-transplant lymphoproliferative disorder after allogeneic hematopoietic cell transplantation

Abstract

Abstract Introduction: Reactivation of Epstein-Barr virus (EBV) is common in allogeneic hematopoietic cell transplantation(allo-HCT). EBV related post-transplant lymphoproliferative disorder (EBV-PTLD) is a rare but life-threatening complication after allo-HCT. Early clearance of B cells may eliminate the proliferation sites of EBV, reducing the incidence of EBV reactivation and mortality of EBV-PTLD Aims: To explore the efficacy of early single low dose of rituximab after allo-HCT on the incidence of EBV viremia and EBV-related PTLD. Methods: From August 2024 to April 2025, a total of 37 patients with hematological disease underwent allo-HCT at Chengdu BOE Hospital and Shanghai Lu Daopei hematology Hospital. All patients was EBV-specific IgG positive before HCT. All patients received ATG based conditioning, and letermovir for CMV prophylaxis. All patients were treated with rituximab 200mg on the 5th day after stem cell reinfusion (the dose for children was adjusted according to their weight). EBV screening is performed once a week by q-PCR and more frequent if EBV DNA positive. Recurrent EBV viremia is diagnosed by detection of EBV-DNA in plasma. PTLD was screened in patients with EBV viremia by lymph node ultrasound and biopsy if needed. The incidence of EBV viremia and PTLD within 100 days and treatment-related toxicity was retrospectively analyzed, and the incidence of GVHD, CMV reactivation, and the survival status was observed. Results: The median age of the patients was 29 years (range, 8-62). 23 patients were females and 14 were males. Diagnosis was acute myeloid leukemia in 5 patients, acute lymphocytic leukemia/lymphoblastic lymphoma in 30 patients and severe aplastic anemia in 2 pts. The stem cell donors were from matched sibling donors in 5 patients, unrelated donors in 4 patients, cord blood in one patient, and haploidentical donors in 27 patients. The median follow-up was 162 days (101〜285 days). Of the 37 patients, only 3（8%）developed EBV viremia in 100 days, persisting from 1 to 2 weeks, none of the patients developed PTLD. There were no severe adverse effect or aggravated infection events during the medication process. Cumulative incidences (CI) at day +100 of grade II-IV and grade III-IV aGVHD were 10.8% and 2%, respectively. Incidence of CMV reactivation was 10.2%. Till last follow up, all the patients presented with B-cell deficiency and hypoimmunoglobulinemia, requiring immunoglobulin replacement therapy. 36 patients were still alive with disease free and 1 died of acute GVHD. Conclusion: Our study shows that early single low dose of rituximab after allo-HCT can significantly reduce incidence of EBV viremia and the risk of EBV-related PTLD, without severe adverse effect despite delayed humoral immune reestablishment. It will provide an effective prophylactic strategy for patients at high risk of EBV and reduce transplant-related mortality after allo-HCT.