A 9-year-old boy received a haploidentical bone marrow (BM) and GCSF mobilized PBSC transplant from his biological father for TM treatment, and an HLA-mismatched umbilical cord blood (UCB) transplant from an unrelated donor 6 days later. The patient's preparation regime consisted of CTX, BU, FLU, ATG, and thiotepa (TT). GVHD prophylaxis included post-transplant CTX, MMF, and tacrolimus (FK506). Neutrophil engraftment, delayed owing to UCB engraftment, was observed by day 40 post-transplantation with an absolute neutrophil count greater than 0.5 x 109 cells/L. On day 79 post-transplantation, the patient was treated for CMV reactivation with IVIG. Critical complications, including severe GVHDs, refractory pancytopenia, and life-threatening infections were not observed.
Patient B returned to the hospital with intermittent fever and enlargement of the lymph nodes of the neck and groin on day 89 post-transplantation. An ultrasound revealed that largest lymph node in the neck was 2.6 cm x 1.0 cm. Chest CT scans showed enlarged mediastinal and bronchial lymph nodes without significant pulmonary lesions (Figure 1D). PCR revealed plasma EBV-DNA (1.08 x 105 copies/mL). Post-transplant lymphoproliferative disorder (PTLD) was suspected but could not be confirmed owing to the refusal of the patient's parents to provide consent for a lymph node biopsy. A positron emission tomography-CT (PET-CT) scan revealed enlarged lymph nodes with increased uptake of fluorodeoxyglucose in the neck, mediastinum, abdomen, and groin, supporting a diagnosis of PTLD. Consequently, the patient was administered foscarnet sodium, and rituximab once weekly for 3 weeks, a course of CTX, and a donor-derived EBV-specific cytotoxic T lymphocyte infusion between day 89 and 114 post-transplantation. The patient also received broad-spectrum antibiotics and prophylactic antifungals. The patient tested negative for EBV-DNA after receiving the first dose of rituximab.
Two weeks after the onset of symptoms, the patient had accelerated chest pain and breathing difficulties. On day 114 post-transplantation, biopsies of the lymph nodes in the neck were performed showing granulomas with caseous necrosis, indicating lymph node TB. On day 116 post-transplantation, AFB testing confirmed TB, and treatment with isoniazid, rifampin, pyrazinamide, levofloxacin, and linezolid was started immediately. The patient did not improve and developed severe chest pain, tachypnea, hypoxemia, and orthopnea within 5 days of the initiation of anti-TB treatment. Chest CT scans revealed bronchial stenosis in both bronchial tubes and worsening lymphadenectasis. A bronchoscopy revealed multiple granulomas severely restricting the primary bronchi (Figure 1G, H). AFB testing was negative; however, BAL fluid tested positive for Mtb by PCR.
Patient B developed type 1 respiratory failure after a week. Chest CT scans revealed massive infiltration, consolidation, and atelectasis of the right upper lobe of the lung, suggesting pulmonary TB (Figure 1E). The patient was then put on a ventilator after 3 days. Cryosurgery was performed via bronchoscopy to remove the granulomas and open the airways (Figure 1I). After a second cryosurgery, the patient showed gradual improvement. On day 155 post-transplantation, a bronchoscopy showed clearance of granulomas from the bronchi (Figure 1J). On day 166 post-transplantation, chest CT scans revealed the dissolution of the majority of pulmonary infiltrates, and the patient was discharged (Figure 1F). He was prescribed oral rifapentine, isoniazid, pyrazinamide, and linezolid for a week, and then changed to rifapentine, isoniazid, and pyrazinamide treatment for the following 4 weeks. Pyrazinamide was discontinued after a month owing to elevated liver enzyme levels and as of the writing of this case report, the patient continues to receive oral rifapentine and isoniazid.