Critical Illness Immunosuppression: Ultra-Rapid Taper to Monotherapy

Abstract

<h3>Purpose</h3> Immunosuppression (IS) is a critical component leading to the success of heart transplantation (HT). However, clinicians need to balance the risks of infection with the need for adequate rejection prophylaxis. Most programs maintain the highest levels of IS in the first 2-3 months following HT. With recent allocation changes which prioritize critically ill candidates, the acuity of such patients (pts) is rising. <h3>Methods</h3> At our institution, standard IS consists of tacrolimus (TAC), steroids and mycophenolate mofetil (MMF). Induction therapy is given for selected pts, particularly with severe hemodynamic instability or multiorgan dysfunction. For pts where the risk of rejection is outweighed by the risk of infection, we have established a critical illness IS protocol where MMF and steroids are stopped within 2-3 weeks of txp. Rejection was defined as ISHLT grade 2R or higher. Outcomes are described. <h3>Results</h3> From May '19 to July '21 there were 64 adult HT performed. Of these, 6 pts were given critical illness IS. The median recipient age was 63.5 years old (IQR 50.1-66.6), 2 were male, most dilated cardiomyopathy. Half were UNOS Status 1 pre-HT, one was status 3 and two were status 4 (stable ventricular assist device). 4/6 had severe primary graft dysfunction (PGD) following HT requiring ECMO and the others had severe coagulopathy and massive bleeding. 4 of 6 received at least one dose of induction antibody. Pts were weaned to TAC monotherapy over a mean of 18.2 +/- 4.4 days post-HT (range 13-25). The pts underwent 11.7 +/- 3.7 biopsies. One pt died of overwhelming sepsis at day 42 but the others are all alive with median follow-up of 282 days (IQR 77.2-568.2). No pt required resumption of corticosteroids or MMF. <h3>Conclusion</h3> Transplant IS is a delicate balance between the risk of severe rejection and the risk of infection. We describe ultra-fast tapering of IS in a cohort of mostly severe PGD recipients. It is feasible to treat highly selected pts with single-drug IS when the risk/benefit equation favors this approach.