DP105 | SIROLIMUS INSTEAD OF CYCLOSPORINE A IN PATIENTS WITH THROMBOTIC MICROANGIOPATHY ASSOCIATED WITH ALLOGENEIC TRANSPLANTATION (TA-TMA): SINGLE-CENTRE EXPERIENCE

Transplant associated Thrombotic microangiopathy (TA-TMA) can be a serious complication following allogeneic transplantation. cyclosporine A (CyA) use can be a trigger. In this study, we analyzed the incidence of TA-TAM and the efficacy of replacing CyA with sirolimus (SIR). From July 2021 to December 2024, 155 patients underwent an allogeneic transplant. TA-TMA screening was performed 1 time per week including LDH, haptoglobin, proteinuria and creatininuria, and renal function. Jodele's diagnostic criteria were used. Standard risk (SR) TA-TMA was defined by the absence of organ damage and in those patients CyA was replaced by SIR since April 2023. High risk (HR) TA-TMA was treated by eculizumab or ravulizumab. Primary endpoints are TA-TAM incidence and to focus on the outcome of standard risk TA-TMA switched to SIR. EASIX score was calculated before allo-SCT. Median follow-up was 22 months (2-40 months). The incidence of TA-TMA was 23% (28/122) (Table): 18% (5/28) were at HR and 82% (23/28) at SR. Before April 2023, in 7 SR TA-TMA, CyA was continued because 3 were secondary to infection, and 1 died from cerebral hemorrhage; 3 improved spontaneously. From April 2023, in 16 SR TA-TMA, CyA was replaced by SIR in 11/16 (69%) and complete remission was achieved in 9/11 (82%). 2 not responding patients were treated with eculizumab (1) and ravulizumab (1). 5/16 (31%) continued CyA because of VOD (1), aGVHD (1), CMV reactivation (1). In 2 patients, TA-TMA progressively improved without change. 5/11 patients (46%) on SIR developed grade II-III acute GVHD. Five patients with HR TA-TMA were treated with Eculizumab (4) and Ravulizumab (1). Complete response was observed in 4/5 patients. In 2 patients, triggering cause (GVHD) was treated. For the whole TA-TMA cohort, 1-y OS was 58%, 60% in HR and 57% in SR. The median EASIX score was 1.1 (range 0-115) for the whole cohort, and 1.8 (range 0.5-115) and 0.95 (range 0.2-20), in patients with or without TA-TMA, respectively. In this study, the global incidence of TA-TMA was 23%, and this was higher than a previous period (2010-2021, incidence 3% data not shown). This difference was attributable to systematic check of TA-TMA signs. This study suggests that in SR TA-TMA, SIR allows to obtain high response rate even if half of them developed aGVHD. In HR TA-TMA, the response rate to complement inhibitors was good.