Incidence and Impact of Endothelial Dysfunction Events and Veno-Occlusive Disease in Haploidentical Stem Cell Transplantation with Post-Transplant Cyclophosphamide: A Retrospective Analysis From the Argentinian Group of Marrow Transplant and Cellular Therapy (GATMO-TC).

Endothelial dysfunction events (EDE) and veno-occlusive disease (VOD) are clinically relevant early complications after hematopoietic stem cell transplantation (HSCT). Data in haploidentical HSCT (HaploSCT) using post-transplant cyclophosphamide (PTCy) are limited in Latin American settings. We conducted a retrospective multicenter study including 310 consecutive adult patients (≥18 years) undergoing unmanipulated HaploSCT with PTCy between 2015 and 2022 across 8 centers in Argentina. EDE was defined as a composite endpoint including VOD, transplant-associated microangiopathy (TMA), renal dysfunction, diffuse alveolar hemorrhage (DAH), and posterior reversible encephalopathy syndrome (PRES); acute GvHD (aGvHD) was analyzed separately (MAGIC criteria). VOD cases were re-adjudicated using EBMT criteria as the standard. Disease risk was categorized using the disease risk index (DRI). All patients received ursodeoxycholic acid prophylaxis and PTCy-based GvHD prophylaxis. Cumulative incidence functions were estimated with competing risks and compared with Gray's test; Fine-Gray models were used for multivariable analyses. Overall survival (OS) was analyzed by Kaplan-Meier and log-rank testing (2-sided P < .05). Median age was 42 years (range 18 to 77) and median follow-up was 37.7 months. Most patients received myeloablative conditioning (75.2%); conditioning backbone was busulfan-based in 54.0%, TBI-based in 34.6%, and melphalan/other in 11.4%. At 1 year, cumulative incidence of EDE (composite including VOD) was 5.5% (95% CI 3.0 to 8.0), with median time to first EDE 30.5 days (IQR 16.3 to 36.8). Among 18 EDE cases, phenotypes were VOD (n = 9; 50.0%), transplant-associated microangiopathy (TMA) (n = 5; 27.8%), renal dysfunction (n = 2; 11.1%), diffuse alveolar hemorrhage (DAH) (n = 1; 5.6%), and posterior reversible encephalopathy syndrome (PRES) (n = 1; 5.6%). Patients aged ≤25 years had higher EDE incidence than >25 years (11.5% [95% CI 3.9 to 19.0] versus 3.8% [95% CI 1.3 to 6.2]; Gray P = .021). In multivariable Fine-Gray regression, age ≤25 years was the only independent predictor of EDE (SHR 4.26; 95% CI 1.42 to 12.74; P = .01). By day 100, cumulative incidence of grade II to IV and grade III to IV aGvHD was 29.8% (95% CI 24.2 to 35.4) and 9.0% (95% CI 5.3 to 12.8), respectively; EDE was associated with higher aGvHD incidence (SHR 3.14; 95% CI 1.47 to 6.68; P = .003). Median time to VOD diagnosis was 25 days (range 8 to 57); 44.4% were classical (≤21 days) and 55.6% late-onset, with severe VOD comprising 55.6%. Three-month VOD incidence was higher in patients ≤25 years (8.6% [95% CI 2.0 to 15.3]) versus >25 years (1.2% [95% CI 0.0 to 2.7]; Gray P = .001). OS was worse in patients with EDE (log-rank P = .014): median OS 7.9 months (95% CI 2.3 to 15.5) versus 23.4 months (95% CI 16.3 to 29.6), and 2-year OS 25.0% (95% CI 6.7 to 49.1) versus 49.6% (95% CI 43.2 to 55.7). In this multicenter adult HaploSCT-PTCy cohort, EDE and VOD were infrequent but associated with substantially inferior OS. Age ≤25 years consistently identified a higher-risk subgroup for EDE and VOD, supporting intensified surveillance and early recognition strategies in this platform.