Post-transplant thrombotic microangiopathy (TMA) is a multi-factorial complication of allogeneic hematopoietic cell transplantation (allo-HCT) whose incidence is increased when using a sirolimus plus tacrolimus regimen for acute graft-versus-host disease (aGVHD) prophylaxis. We evaluated the incidence and possible risk factors for TMA in a case series of 177 patients who received allo-HCT using SIR/TAC-based GVHD prophylaxis. Donors were either sibling (n=82) or matched unrelated (n=95). Within the first 100 days post-HCT, 30 (17%) patients were diagnosed with TMA, and an additional nine patients (5%) were classified as probable TMA cases. The median time to TMA onset was 4.6 weeks (range: 1.6-10.6). Thirty-four patients developed both TMA and aGVHD, with the majority of patients (81%) developing aGVHD first. By multivariable analysis, the following factors were found to be associated with increased risk of TMA: day 14 serum sirolimus: ≥9.9 ng/ml (HR: 2.19, 95% CI: 1.13-4.27, p=0.02), presence of prior aGVHD grades II-IV (HR: 3.04, 95% CI: 1.38-6.71, p<0.01), and fully myeloablative conditioning (HR: 3.47, 95% CI: 1.60-7.53, p<0.01). The risk factors for TMA suggest that when using sirolimus/tacrolimus for GVHD prophylaxis, careful monitoring and adjustment of sirolimus dosages is critical, particularly in patients with active aGVHD.

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Preformed and posttransplant ndDSA were associated with AMR. C3d + DSA correlates with complement deposition on the graft and higher risk of AMR which may permit the application of personalized immunotherapy targeting the complement pathway.

Early detection and adequate duration of therapy for ESBL-producing Enterobacteriaceae in solid organ transplants and MCS device recipients are essential in successful patient outcomes including prevention of recurrent infection.

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