Trends of Maintenance Immunosuppression in Hand and Facial Transplantation
Amit K. Manjunath, BS1, Rami S. Kantar, MD2, Michael J. Cammarata, BS2, Adam Jacoby, MD2, William J. Rifkin, BA2, Bruce E. Gelb, MD3, Rodrigo Diaz-Siso, MD2, Eduardo D. Rodriguez, MD, DDS2.
1NYU School of Medicine, New York, NY, USA, 2Hansjörg Wyss Department of Plastic Surgery, NYU Langone Health, New York, NY, USA, 3Department of Surgery, NYU Langone Health, New York, NY, USA.
In select patients, vascularized composite allotransplantation (VCA) offers functional and aesthetic outcomes superior to autologous reconstruction. However, its role in the reconstructive armamentarium is limited by the need for life-long immunosuppression. Furthermore, some studies have suggested that skin-containing VCA requires greater maintenance immunosuppression than solid organ transplants due to higher antigenicity. This study evaluates trends of maintenance immunosuppression in skin-containing VCA recipients and kidney recipients to determine differences in therapeutic risk.
VCA immunosuppression data were collected through a review of hand and face transplant literature. Kidney transplant immunosuppression data were collected through an institutional review board-approved retrospective chart review of a randomly selected group of 100 patients whose transplants were performed between 1997 and 2016. Data from patients younger than 18, patients not receiving triple maintenance immunosuppression therapy, and patients with missing immunosuppression information were excluded from the analysis. Prednisone doses (mg/day) and mycophenolate mofetil (MMF) doses (gm/day) were compared between VCA and kidney recipients at predefined follow-up intervals (<1, 1-5, and >5 years). Tacrolimus target trough levels (TTTL) were stratified into our institution's kidney transplant risk-based target ranges (low risk: 4-6 ng/ml, high risk: 6-8 ng/ml) or higher (>8 ng/ml). The distribution of VCA recipient and kidney recipient TTTL was calculated at follow-up intervals of 1-5 and >5 years within each cohort.
Immunosuppression data were available for 57 VCA recipients and 98 kidney recipients. There were no significant differences in prednisone doses between groups at all follow-up intervals. While the mean MMF dose of VCA recipients was significantly greater than that of kidney recipients at less than 1 year (1.71 ± 0.58 vs. 1.16 ± 0.55 gm/day; p=0.01), there was no significant difference at subsequent follow-up intervals. For VCA recipients, there was a significant difference (p=0.02) in TTTL distribution over the three predefined therapeutic ranges (4-6 ng/ml, 6-8 ng/ml, >8 ng/ml, respectively) between 1-5 years (24.0%, 20.0%, 56.0%, respectively) and greater than 5 years (28.6%, 42.9%, 28.6%). Kidney recipients showed no significant difference in TTTL distribution over the three defined therapeutic ranges (4-6 ng/ml, 6-8 ng/ml, and >8 ng/ml) between the follow-up intervals.
At longer follow-up, VCA and kidney recipients receive comparable MMF and prednisone doses. In addition, the majority of VCA recipients are treated with TTTL similar to kidney recipients after 5 years. These findings suggest that VCA recipients may not be subject to a higher level of dose-related immunosuppressive therapeutic risk than kidney recipients at longer follow-up. While the benefits of VCA have proven difficult to quantify, a detailed understanding of therapeutic risk may serve to enhance the informed consent process. Transparent outcome reports are warranted to determine safe and effective strategies for minimization of immunosuppression in VCA.
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