An unexpected cause of pancytopenia after allogeneic bone marrow transplant

The patient was a 56-year-old man with Philadelphia chromosome-negative acute lymphoblastic leukaemia (ALL) treated recently with stem cell transplant, who presented with fever of unknown origin, thrombocytopenia and failure to thrive. He received a haploidentical (brother) stem cell transplant 2 months earlier; engraftment occurred 1 month post-transplant. In the hospital, he developed altered mental status and acute respiratory failure. Computed Tomography (CT) of the brain was negative for acute pathology. Chest X-ray revealed pericardial effusion, bilateral pleural effusions and bilateral diffuse pulmonary opacities. Blood and urine cultures were negative as well as extensive infectious workups including viral polymerase chain reactions (PCRs) and testing for fungal and parasitic organisms. Despite being on broad-spectrum antibiotics, his condition continued to deteriorate. His family decided to de-escalate the care to comfort care only and the patient died shortly after. At autopsy, bone marrow sampling revealed rare cyst-like structures containing crescent-shaped organisms (top left, haematoxylin and eosin, objective ×100). Immunostain confirmed the diagnosis of Toxoplasma gondii infection (top right, T. gondii, objective ×100). Parasites were found in multiple organs including the heart and lungs (bottom left and right, respectively, haematoxylin and eosin, objective ×100). Retrospective examination of the antemortem marrow, however, showed no stainable organisms. Post-transplant infection by T. gondii is rare and occurs due to alterations in host immunity in the early post-engraftment period (days 30–100). The estimated incidence is 0.25% in the United States in patients undergoing allogenic bone marrow transplant. Patients with pretransplant immunoglobulin G (IgG) positivity are at particularly high risk, as in this patient. However, tissue biopsy is often of low yield due to sparse organisms present. The classic ring-enhancing lesions may or may not be present on brain magnetic resonance imaging (MRI) or CT scan despite clinical symptoms of cerebral involvement.1 In the current case, despite the patient's altered mental status, brain imaging did not show obvious lesions. This case illustrates that diagnosing T. gondii infection after transplant is extremely challenging, and most reported cases are diagnosed post-mortem.2 As clear guidelines are currently lacking for testing T. gondii after bone marrow transplant, clinical suspicion needs to be high, and empirical treatment might be required before diagnosis can be established.