Toxoplasmosis after allogeneic haematopoietic cell transplantation: experience using a PCR-guided pre-emptive approach.

ABSTRACT

OBJECTIVES: Prophylaxis with trimethoprim-sulphamethoxazole (TMP-SMZ) is recommended in Toxoplasma-seropositive allogeneic haematopoietic cell transplant (HCT) recipients to prevent reactivation, but it is associated with numerous side effects. We report our experience of a pre-emptive approach guided by a polymerase chain reaction (PCR) in patients not receiving prophylaxis. METHODS: In this retrospective, single-centre experience, seropositive recipients and seronegative recipients receiving a graft from a seropositive donor were screened by PCR for the presence of Toxoplasma gondii DNA in peripheral blood until at least 6 months after transplantation. Confirmed PCR positivity triggered a pre-emptive anti-Toxoplasma therapy. Cases of Toxoplasma reactivation (using the European Society for Blood and Marrow Transplantation definitions) were compared with four controls (without reactivation), matched in time and recipient serostatus, to identify risk factors for reactivation by multivariate analysis. RESULTS: From November 2001 to August 2020, 1455 consecutive adult patients (59 cases and 1396 controls) were screened. The overall 1-year cumulative incidence of toxoplasmosis was 4.1% and the 1-year cumulative incidence in the seropositive recipients was 8.8%. Reactivation was associated with second transplant (OR 2.51, 95%CI 1.28-4.94, p 0.011), myeloablative conditioning (OR 2.24, 95%CI 1.17-4.41, p 0.011), total body irradiation (OR 2.29, 95%CI 1.17-4.44, p 0.010), acute graft-versus-host disease (GvHD) (OR 2.27, 95%CI 1.26-4.08, p 0.008) and use of high-dose corticosteroids (OR 2.08, 95%CI 1.14-3.78, p 0.018). In multivariate analysis only acute GvHD remained significant (adjusted OR 2.54, 95%CI 1.16-5.71, p 0.021). CONCLUSIONS: A PCR-based pre-emptive approach might serve as an acceptable alternative for patients unable to start with or to continue TMP-SMZ prophylaxis. Acute GvHD was identified as the single independent predictor for reactivation.