Epstein-barr virus DNAemia monitoring for the management of post-transplant lymphoproliferative disorder.

BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is a potentially fatal complication of allogeneic hematopoietic cell transplantation (HCT). Epstein-Barr virus (EBV) reactivation (detectable DNAemia) predisposes to the development of PTLD. METHODS: We retrospectively studied 306 patients monitored for EBV DNAemia after Thymoglobulin-conditioned HCT to determine the utility of the monitoring in the management of PTLD. DNAemia was monitored weekly for ≥12 weeks post-transplantation. RESULTS: Reactivation was detected in 82% of patients. PTLD occurred in 14% of the total patients (17% of patients with reactivation). PTLD was treated with rituximab only when and if the diagnosis was established. This allowed us to evaluate potential DNAemia thresholds for pre-emptive therapy. We suggest 100,000-500,000 IU per mL whole blood as this would result in unnecessary rituximab administration to only 4-20% of patients and near zero mortality due to PTLD. After starting rituximab (for diagnosed PTLD), sustained regression of PTLD occurred in 25/25 (100%) patients in whom DNAemia became undetectable. PTLD progressed or relapsed in 12/17 (71%) patients in whom DNAemia was persistently detectable. DISCUSSION: In conclusion, for pre-emptive therapy of PTLD, we suggest threshold DNAemia of 100,000-500,000 IU/mL. Persistently detectable DNAemia after PTLD treatment with rituximab appears to have 71% positive predictive value and 100% negative predictive value for PTLD progression/relapse.

Risk factors for post-transplant lymphoproliferative disorder after Thymoglobulin-conditioned hematopoietic cell transplantation.

Epstein-Barr virus (EBV)-induced post-transplant lymphoproliferative disorder (PTLD) occurs frequently when rabbit antithymocyte globulin (ATG) is used in hematopoietic cell transplant (HCT) conditioning. We retrospectively studied 554 patients undergoing ATG-conditioned myeloablative HCT. Strategies used to minimize mortality due to PTLD were either therapy of biopsy-diagnosed PTLD in the absence of EBV DNAemia monitoring (n = 266) or prompt therapy of presumed PTLD (based on clinical/radiologic signs and high EBV DNAemia, in the setting of weekly EBV DNAemia monitoring) (n = 199). Both strategies resulted in similar mortality due to PTLD (0.7% vs 1% at 2 years, P = .43) and similar overall survival (63% vs 67% at 2 years, P = .23) even though there was a trend toward higher PTLD incidence with the prompt therapy. Donor positive with recipient negative EBV (D+R-) serostatus was a risk factor for developing PTLD. Older patient age, HLA-mismatched donor, and graft-versus-host disease were not associated with increased risk of PTLD. In summary, in ATG-conditioned HCT, D+R- serostatus, but not older age, mismatched donor or GVHD is a risk factor for developing PTLD. EBV DNAemia monitoring may be a weak risk factor for developing/diagnosing PTLD; the monitoring coupled with prompt therapy does not improve survival.

A Pharmacist-Managed Hydroxyurea Prescribing Protocol Improves Uptake and Optimization among Patients with Sickle Cell Disease.

Sickle cell disease (SCD) is a common genetic disorder with potentially serious sequelae that can be effectively treated with hydroxyurea. Despite its favorable benefit-risk profile, hydroxyurea uptake in patients with SCD is low. A pilot study was conducted at the Southern Alberta Rare Blood and Bleeding Disorders (SARBBDs) Comprehensive Care Program between January 2020 and September 2023 to assess the implementation of a pharmacist-led protocol for supporting the uptake of hydroxyurea among eligible patients with SCD and optimizing its dosing. The protocol standardized the prescription, monitoring, dose titration, and patient counselling by a clinic pharmacist. The number of patients enrolled in the SARBBDs program increased from 98 in January 2020 to 168 in 2023. During this period, the proportion of patients on hydroxyurea increased from 37.8% to 62.5%, the proportion of patients on hydroxyurea who were at a maximum tolerated dose (MTD) increased from 35.1% to 63.8%, and the average hemoglobin F level increased from 13.9% to 19.7%. The mean time to reach MTD was 10 months and required eight pharmacist interventions, six laboratory assessments, and three dose increases. Hydroxyurea continuation rates were high, with most discontinuations resulting from loss to follow-up or transition to a transfusion management strategy. This real-world pilot study demonstrated that implementation of a pharmacist-led prescribing and monitoring protocol nearly doubled hydroxyurea uptake and achievement of MTD in patients with SCD managed in a rare blood disorders clinic.