Usefulness and limitations of polymerase chain reaction (PCR) for the diagnosis and management of toxoplasmosis following allogeneic hematopoietic cell transplant: Single center experience with 31 patients over 16 years

Background Toxoplasmosis is an early post-transplant complication in recipients of allogeneic hematopoietic cell transplant (HCT), typically arising from reactivation of latent infection. Toxoplasma gondii PCR has improved detection. Methods Single center, retrospective review of allogeneic HCT recipients who developed toxoplasmosis from August 2008 to November 2024. Results We identified 31 cases of toxoplasmosis among 1,235 HCT recipients. Ten had infection and 21 had end-organ disease. Fever was the most common clinical manifestation (74.2%). Patients with pulmonary or CNS disease often lacked organ-specific symptoms. Toxoplasmosis primarily occurred in patients not on prophylaxis (90.3%), at a median of 28 days post-HCT (IQR 20 to 69 days). Whole blood Toxoplasma PCR diagnosed 80.6% cases and showed a cumulative sensitivity of 93.3%. However, PCR was not always positive at symptom onset, and some asymptomatic patients already had end-organ disease at the time of first PCR positivity. Trimethoprim-sulfamethoxazole (TMP/SMX) was the most used treatment (48.4%). Mortality directly attributable to toxoplasmosis was 12.9%, but all-cause mortality was 61.3%. Conclusions Toxoplasmosis is an early post-HCT complication with high morbidity and mortality. Prophylaxis is essential. TMP-SMX is effective, but sometimes it is withheld early post-HCT due to potential myelotoxicity. Given the short time window between infection and progression to disease, we recommend twice-weekly monitoring with whole blood PCR while off TMP-SMX and early initiation of TMP-SMX post-HCT for Toxoplasma seropositive patients. Atovaquone may be considered as a bridging prophylaxis until TMP-SMX is started, but its absorption may be compromised early post-HCT and breakthrough cases have been reported.