An 8-year-old girl with TM received granulocyte colony stimulating factor mobilized peripheral blood stem cells (PBSCs) from an unrelated human leukocyte antigen (HLA) 9/10 matched donor. The myeloablative conditioning regimen consisted of cyclophosphamide (CTX), busulfan (BU), fludarabine (FLU), and rabbit anti-thymocyte globulin (ATG). Graft-versus-host disease (GVHD) prophylaxis included cyclosporine (CSA), low dose methotrexate (MTX), and mycophenolate (MMF). Neutrophil engraftment was achieved by day 14 post-transplantation. The donor cell chimerism was >99%. Patient A was discharged on day 25 post-transplantation without severe complications.
The patient was readmitted for persistent high fever and cough on day 73 post-transplantation. Chest computed tomography (CT) scans suggested mild pneumonia without severe pulmonary lesions (Figure 1A). Despite the administration of broad-spectrum antibiotics and antifungal treatments, the patient developed severe respiratory distress requiring ventilatory support starting on day 82 post-transplantation. A bronchoscopy was performed at this time. Bronchoalveolar lavage (BAL) fluid tested positive for Mtb DNA (2.79 x 103 copies/mL), cytomegalovirus (CMV) DNA (2.65 x 105 copies/mL), and Epstein-Barr virus (EBV) DNA (8.68 x 104 copies/mL) by real-time PCR analysis. Acid-fast bacilli (AFB) testing of the BAL fluid was negative. Thus, diagnoses of pulmonary TB, CMV, and EBV were considered. Ten days after the patient was hospitalized, TB treatment consisting of isoniazid, rifampin, and pyrazinamide, and antiviral therapy consisting of ganciclovir and intravenous immunoglobulin (IVIG) were initiated. The patient was removed from ventilator support 90 days post-transplantation.
Four days after the removal of the ventilator, the patient developed hematemesis and hemoptysis with continued high fever and persistent cough. A chest CT scan revealed the progression of pneumonia with massive pulmonary infiltrates (Figure 1B). The patient was again placed on a ventilator, and pneumorrhagia was observed during intubation. Streptomycin, linezolid, and levofloxacin were immediately added to the patient's treatment regime and antiviral treatment was changed to ganciclovir and foscarnet sodium. Empiric antibiotic and antifungal treatments were ongoing. The patient developed signs of hemophagocytic lymphohistiocytosis syndrome, including significant enlargement of the liver and spleen, pancytopenia, sudden elevated serum ferritin (18298 mmol/L), and delayed coagulation time. Methylprednisolone was added to the patient's treatment regime. The patient was removed from the ventilator support after showing progress. On day 110 post-transplantation, the patient was discharged and continued on a modified TB treatment regime of oral isoniazid, rifampin, and pyrazinamide. Chest CT scans performed on day 326 post-transplantation revealed almost full resolution of pulmonary infiltrates (Figure 1C). The patient was continued on oral isoniazid, rifampin, and pyrazinamide treatment for a year before the discontinuation of anti-TB treatment.