Outcomes Following Intolerance to Tacrolimus/Sirolimus Graft-versus-Host Disease Prophylaxis for Allogeneic Hematopoietic Cell Transplantation

Abstract

Although tacrolimus and sirolimus (TAC/SIR) is an accepted graft-versus-host disease (GVHD) prophylaxis regimen following allogeneic hematopoietic cell transplantation (HCT), toxicity from this regimen can lead to premature discontinuation of immunosuppression. There are limited studies reporting outcomes and subsequent treatment of patients with TAC/SIR intolerance. This study was conducted to assess the outcomes of patients with TAC/SIR intolerance and guide their subsequent management. We retrospectively analyzed transplantation outcomes of consecutive adult patients at Moffitt Cancer Center who underwent allogeneic HCT with TAC/SIR as GVHD prophylaxis between 2009 and 2018. TAC/SIR intolerance was defined as discontinuation of either TAC or SIR due to toxicity before post-transplantation day +100. A total of 777 patients met the inclusion criteria. The median duration of follow-up was 22 months (range, 0.2 to 125 months). Intolerance occurred in 13% (n?=?104) of the patients at a median of 30 days (range, 5 to 90 days). The most common causes of intolerance were acute kidney injury (n?=?53; 51%), thrombotic microangiopathy (n?=?31; 28%), and veno-occlusive disease (n?=?23; 22%). The cumulative incidence of grade II-IV acute GVHD at 100 days was 50% (95% CI, 39% to 64%) in the TAC/SIR-intolerant patients and 25% (95% CI, 22% to 29%) in patients tolerant to this regimen (P?< .0001). In multivariate analyses, the incidence of grade II-IV 4 acute GVHD was significantly higher in the TAC/SIR-intolerant patients (hazard ratio [HR], 2.40; 95% CI, 1.59 to 3.61; P?

View details for DOI 10.1016/j.jtct.2022.01.003

View details for Web of Science ID 000798213900006

View details for PubMedID 35017119