Impact of Dyslipidemia on Allogeneic Transplantation Outcomes and Cardiovascular Mortality in Patients with Acute Leukemias in the Post-Transplant Cyclophosphamide Era

Background/Objectives: Allogeneic hematopoietic stem cell transplantation is associated with increased cardiovascular risk driven by endothelial dysfunction, chronic inflammation, and treatment-related metabolic disturbances, including dyslipidemia. In the contemporary era of post-transplant cyclophosphamide-based prophylaxis, the prognostic significance of dyslipidemia—particularly as assessed by non-HDL cholesterol—remains unclear. In this study, we aimed to compare the engraftment days, graft-versus-host disease (GVHD) development, relapse, overall survival rates, and cardiovascular mortality in patients using myeloablative/reduced intensity conditioning regimens with post-transplant cyclophosphamide (PTCy) 50 mg/kg/day for 2 days in patients with acute leukemias. Methods: A total of 95 adult patients with acute leukemias were included in their first remission who underwent matched sibling donor transplantation with PTCy (50 mg/kg on days +3 and +4). Patients were stratified according to pre-transplant non-HDL-C levels (<160 mg/dL vs. ≥160 mg/dL). Matched related donors were selected for the patients. All patients received either myeloablative or reduced-intensity conditioning based on EBMT criteria, with fludarabine-based combinations including busulfan, treosulfan, or TBI, along with ATLG administered at a total dose of 15 mg/kg. Peripheral blood stem cells were used for all transplants, and GVHD prophylaxis consisted of cyclosporine. Results: Platelet (median 13 vs. 14 days) and neutrophil (median 14 vs. 15 days) engraftment times and veno-occlusive disease (VOD) rates were comparable across groups (all p > 0.05); cumulative incidences of grade II–IV aGVHD at +100 days, grade III–IV aGVHD at +100 days, and moderate-severe cGVHD at 1 year, relapse-free survival, and non-relapse mortality at 1 year were comparable in two cohorts (all p > 0.05). GVHD-free/relapse-free survival (GRFS) at 1 year was also comparable across groups (p = 0.15). Median GRFS was 150 (95% CI: 120–330) days and 270 (95% CI: 154-not reached) days, respectively [HR was 0.68 (0.40–1.15), p = 0.15; GRFS at 1 year was 66.6% vs. 52.0%, respectively]. The groups were also comparable in terms of overall survival (OS). Follow-up ranged from 0.5 to 108 months, and median follow-up was 60 months in two cohorts. Median OS was not reached in non-HDL-C < 160 (95% CI: 70 months–not reached) and 67 months in non-HDL-C ≥ 160 groups (95% CI: 13 months–not reached) (Log rank = 0.21). No cardiovascular death events occurred during the follow-up period. Conclusions: In this homogeneous matched sibling donor transplant cohort with extended follow-up and uniform administration of post-transplant cyclophosphamide, cyclosporine-based GVHD prophylaxis, and anti-thymocyte lymphoglobulin (ATLG), pre-existing dyslipidemia was not associated with an adverse impact on GRFS, NRM, PFS, CMV reactivation, OS or long-term cardiovascular mortality.