https://orcid.org/0000-0002-9268-9655
Key Points
PTCy uniquely alters vascular biomarkers, with an increase in Ang-2 and a decrease in EGF at day +28 post-transplant.
Tac/Sir regimen also alters vascular biomarkers, increasing follistatin and endoglin, and decreasing VEGFR2.
Abstract
Post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis regimens are associated with very low rates of severe acute and chronic GVHD after hematopoietic cell transplant (HCT). However, concerns about cardiac and other organ toxicities persist. This study aimed to compare the vascular biomarker profile of PTCy with other GVHD regimens, including Tacrolimus/Sirolimus (Tac/Sir) and Tacrolimus/Methotrexate (Tac/MTX), to generate hypotheses for toxicity mitigation strategies. Plasma samples from day +28 post-transplant were analyzed against pre-transplant baseline measurements in patients receiving PTCy-based GVHD prophylaxis as part of BMT CTN (Blood and Marrow Transplant Clinical Trials Network) 1202 (N=112), versus Tac/MTX (N=98) and Tac/Sir (N=95) regimens from BMT CTN 0402. Compared to Tac/MTX, PTCy was associated with increasing angiopoietin-2 levels and decreasing epidermal growth factor levels at day +28. In contrast, Tac/Sir displayed increasing follistatin and endoglin levels and decreasing VEGFR2 plasma levels after HCT. Across all cohorts, increasing epidermal growth factor (EGF) was protective from non-relapse mortality, and decreasing VEGFR2 was associated with subsequent development of extensive chronic GVHD. These distinct biomarker profiles offer insights that could guide strategies to mitigate unique GVHD prophylaxis-associated toxicities.
