Table 3.
Summary of recent reported EBV preventative strategies using rituximab in HCT
| Study | Patients and HCT Protocol | Monitoring | Sample | Pre-emptive EBV threshold |
Treatment details | EBV reactivation and PTLD rates |
|---|---|---|---|---|---|---|
| Jain et al. 2019 [37, 38] | N = 488 myeloablative and non-myeloablative HCT GVHD Px included a selection of TAC, MMF, MTX ATG 2.5-7.5mg/kg in 306/488 patients |
Weekly until day 100, or beyond this if GVHD, immunosuppressants or previous EBV PTLD. Repeat testing every 3-5 days after reactivation |
Whole blood | >2,000copies/mL and continues to rise on a weekly basis; OR 2,000-5,000copies/mL and considered high risk of EBV reactivation; OR >5,000copies/mL |
Pre-emptive rituximab 375mg/m2 weekly | 14% (67/488) EBV reactivations as per criteria 1.4% (7/488) EBV PTLD |
| Van Besien et al. 2019 [49] | N = 198 haplo-cord donors, supplemented by CD34 selected third-party cells to accelerate recovery most commonly FluMel+/−TBI GVHD Px included TAC, MMF, ATG 4.5-6mg/kg, rituximab 375mg/m2, 2 weeks prior to HSCT (n=38), prior treatment with rituximab (n=13), no rituximab (n=147) |
Twice weekly during hospitalization, then weekly for the first 100 days, then second weekly until day180 or as clinically indicated | Not reported | Not reported, PTLD reported based on “rapid increasing EBV levels”, positive PET scan and biopsy proven PTLD | Prophylactic rituximab 375mg/m2 was administered 2 weeks prior to HSCT (n=38) unless prior treatment with rituximab was given for primary B-cell malignancy (n=13). | Prior rituximab: 2% (1/51) EBV viremia (>200 copies/mL). No EBV PTLD No prior rituximab: 18% (27/146) EBV viremia. 12% (16/146) EBV PTLD |
| Ru et al. 2020 [12] | N = 890 Bu/Cy, TBI/Cy, Flu/Bu/Cy or Flu/Bu/Ara-C GVHD Px included CSP, MTX; MMF and ATG for URD and Haplo (27.9%) |
Weekly until day +90, then fortnightly until day +180 | Whole blood | 105 Copies/mL or 104 Copies/mL for 2 weeks | Initially reduction in immunosuppression and treatment with ganciclovir/foscarnet, then pre-emptive treatment with rituximab (no dose given) | 19.6% (175/890) EBV reactivation. 0.7% (7/890) EBV PTLD Incidence of ATG patients not reported separately. The cumulative incidence of EBV reactivation was 2.9%, 11.7%, 27.3%, and 41.9% for patients with 0, 1, 2, and 3 risk factors including ATG, haplo, and GVHD |
| Marzolini et al. 2021 [36] | N = 515 Cy/TBI or Flu/Cy/TBI GVHD Px included Alemtuzumab 20-100mg |
Weekly up to day 100 | Plasma | Only treated if clinical signs of “EBV disease” | Immunosuppression reduced and rituximab 375mg/m2 was administered weekly for 4 weeks | 35% (192/515) EBV reactivation. 3.9% (20/515) EBV disease, 19 PTLD, 1 EBV encephalitis. |
Abbreviations: AraC, cytarabine; ATG, antithymocyte globulin; Bu, busulfan; CSP, cyclosporin; Cy, cyclophosphamide; Flu, fludarabine; GVHD, graft versus host disease; Mel, melphalan; MMF, mycophenolate; MTX, methotrexate; Px, prophylaxis; TAC, tacrolimus; TBI, total body irradiation.