PMC5985128_01
PMC5985128_02
Graphic representation of induction immunosuppression regimen for presented face transplant recipient. The cumulative dose of rabbit antithymocyte globulin (ATG) reached 6 mg/kg (total of 575 mg). Patient also received tacrolimus and mycophenolate mofetil (MMF) en route to the operating room for the facial transplant procedure. The shaded area indicates the initiation of maintenance immunosuppression.
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Based on FCXM results, an induction regimen was designed consisting of rATG 6 mg/kg (575 mg total dose), methylprednisolone taper, and the anti-CD20 agent rituximab (1 g) (Figure 1).
Patient's maintenance tacrolimus trough levels recorded in the posttransplant period. Shaded area represents the target trough levels, which have gradually decreased over time.
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Maintenance immunosuppression has remained stable, with progressive decreases in tacrolimus trough target levels (Figure 2) as well as MMF and prednisone doses (Figures 3 and 4).
Patient's total maintenance dosage of mycophenolate mofetil. Dose reductions were made to mitigate leukopenia requiring filgrastim treatment. Brief treatment interruptions were made in the setting of suspected viral gastroenteritis (postoperative day 87-91) and suspected viral bronchitis (postoperative day 227-229).
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Maintenance immunosuppression has remained stable, with progressive decreases in tacrolimus trough target levels (Figure 2) as well as MMF and prednisone doses (Figures 3 and 4).
Patient's total maintenance dosage of prednisone during posttransplant period.
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Maintenance immunosuppression has remained stable, with progressive decreases in tacrolimus trough target levels (Figure 2) as well as MMF and prednisone doses (Figures 3 and 4).
Patient's posttransplant renal function represented by blood urea nitrogen (BUN) and creatinine levels. Bars represent range of values in a 25-day period; plotted points represent the mean value during the same time period.
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CD3+ and CD19+ lymphocyte subset studies shows depletion of T cells and B cells immediately after induction with rabbit antithymocyte globulin and rituximab. Gradual B cell repopulation began at approximately postoperative day 200, as expected. T cell repopulation is apparent at approximately postoperative day 25; patient has presented prolonged leukopenia.
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The B lymphocyte (CD19+) population reappeared in laboratory studies after approximately POD 200 and has undergone gradual reconstitution. The patient has presented with prolonged neutropenia, treated with filgrastim regimen as needed (Figure 6).
Hematoxylin and eosin (H&E) staining revealed perivascular dermatitis with eosinophils at our 1 year time point (a) and perivascular lymphocytic dermatitis at the 2-year mark (c); C4d staining was negative at our 1 year time point (b) compared with sparse but focal superficial dermal positivity at 2 years after transplant (d). Black arrows indicate inflammatory infiltrates which correspond with focal C4d positivity.
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Histopathology analysis of allograft skin biopsy performed on POD 410 (Table 1) showed sparse perivascular dermatitis with eosinophils (Figure 7(a)), consistent with Banff grade 0-1; C4d immunohistochemistry staining was negative (Figure 7(b)). Histopathology of allograft skin biopsy performed on POD 711 (Table 1) showed focal perivascular lymphocytic dermatitis (Figure 7(c)), consistent with Banff grade 0; C4d immunostain showed focal positivity in the superficial dermis (Figure 7(d)).