Two Case Reports of Successful Withdrawal of Mycofenolate Mofetil After Living Donor Lobar Lung Transplantation

Abstract

We have no personal conflicts of interest or outside support for this research to declare 2 INTRODUCTIONIn most cases of lung transplantation, immunosuppression is maintained using calcineurin inhibitors (CNIs), anti-metabolites and steroids. Lung transplant recipients on such a regimen of triple immunosuppressants are susceptible to infectious diseases.Moreover, many prophylactic antibiotics and laboratory studies are needed, including monitoring of immunosuppressant levels and respiratory function tests, to prevent or predict allograft rejection. However, serum immunosuppressant levels alone may not accurately reflect immune status. ImmuKnow® (Cylex, Columbia, MD) is a novel and promising in vitro assay for measuring the cell function of stimulated T cells. 1 Bhorade et al. 2 reported that ImmuKnow® levels were lower in lung transplant recipients with infection than in non-infected recipients. We report two clinical cases in which mycofenolate mofetil (MMF) was successfully withdrawn after living donor lobar lung transplantation while monitoring patient immune function with the ImmuKnow® assay. CASE REPORT Case 1A 43-year-old woman underwent living donor lobar lung transplantation (LDLLT) for pulmonary alveolar proteinosis. The left lower lobe was donated by her older brother, while the right lower lobe was donated by her husband. Both donors appeared healthy.Postoperative course was uneventful, and she was discharged without any oxygen support. She had been receiving a standard triple immunosuppressant regimen, comprising tacrolimus (target trough level, 15-20 ng/ml for the first 3 months, followed by 10-15 ng/ml), MMF (1500 mg/day), and prednisolone (0.4 mg/kg/day for the first 6 months, followed by 0.2 mg/kg/day). Our prophylactic strategies for fungal, viral, and protozoan infections were oral itraconazole at 100 mg/day, valganciclovir at 900 mg/day, and trimethoprim-sulfamethoxazole at 1 g every other day, respectively. Six months 3 after transplantation, the patient developed invasive pulmonary aspergillosis (IPA). MMF was withdrawn immediately, and the trough level of tacrolimus was reduced to around 5-8 ng/ml to allow the immune status of the patient to recover and battle this fatal infection. The patient was treated with oral voricocazole at 300 mg twice daily, inhalation of amphotericin B at 10 mg 5 times daily, and intravenous micafungin at 300 mg/day.Fortunately, her condition improved over 3 months of hospitalization, and she was discharged without any symptoms. Oral voriconazole and inhaled amphotericin B were continued as prophylaxis for 9 months. Details of the clinical course have been reported previously. 3 Immune function in this patient was monitored using the ImmuKnow® assay from 14 to 37 months after transplantation ( Case 2A 24-year-old man underwent LDLLT for cystic fibrosis. He had paranasal sinusitis, but curative surgery had already been performed before transplantation. The left lower lobe was donated by his father, while the right lower lobe was donated by his uncle. After LDLLT, ...

Infectious Episodes Lead to the Oxidative Stress Response after Lung Transplantation

“…Thus, it is desirable for clinicians to correctly and promptly distinguish and diagnose infections from allograft rejection and treat them. Given the present results, serial measurement of d-ROMs could be an effective tool to identify and monitor the effect of treatment for infections, similar to the ImmuKnow assay reported previously [ 14 ].…”

Severe hematologic complications after lung transplantation in patients with telomerase complex mutations

“…Therefore a procedure with reduced immunosuppression is currently proposed for patients with dyskeratosis congenita [29][30][31]. Some reports suggest that mycophenolate mofetil and azathioprine may be safely removed from the drug regimen following lung transplantation [28,32]. Whether mycophenolate mofetil might be better tolerated than azathioprine in this setting warrants further study.…”

“…None of the treatment was associated with any objective pulmonary improvement assessed either by CT scan or an increase in VC or DLCO by 10% of the predicted value or greater. At the last visit before transplantation, VC and DLCO were 42% [75-22] and 22% [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] of predicted, respectively.…”

De novo malignancy after lung transplantation in Japan

“…To distinguish allograft rejection and infection, a convenient laboratory kit is available by measuring the amount of activated of CD4 ? T cells, and this might help us solve this problem [14].…”