Central Nervous System Toxoplasmosis Beyond HIV in Patients with Hematologic Malignancies: A Contemporary Narrative Review and Illustrative Case Synthesis

Toxoplasmosis is an important opportunistic infection in immunocompromised individuals, typically resulting from reactivation of latent Toxoplasma gondii infection. CNS toxoplasmosis, most commonly presenting as toxoplasmic encephalitis (TE), is rare in patients with hematologic malignancies and after hematopoietic stem cell transplantation (HSCT). It is nevertheless life-threatening and likely underrecognized. This narrative review integrates molecular, immunological, clinical, and transplant-related evidence on T. gondii persistence and reactivation, treatment-associated immune dysfunction, diagnosis, management, prophylaxis, and molecular surveillance. Risk reflects cumulative immunosuppression, particularly impaired T-cell reconstitution, lymphocyte-depleting therapy, corticosteroid exposure, cytopenias, hypogammaglobulinemia, and absent or ineffective prophylaxis. Typical ring-enhancing lesions, positive serology, and detectable T. gondii DNA in cerebrospinal fluid may all be absent. Diagnosis therefore requires integration of immune and treatment history, magnetic resonance imaging, molecular testing, and, when necessary, histopathology. When clinical suspicion is high, empiric therapy should not be delayed; however, diagnostic specimens should be obtained whenever feasible, and evaluation for alternative diagnoses should proceed in parallel. In seropositive allogeneic HSCT recipients, trimethoprim–sulfamethoxazole prophylaxis with quantitative PCR surveillance remains the best-established preventive strategy.