Association of Cyclosporine Dose with Early Onset Hypertension in Allogeneic Hematopoietic Cell Transplant Patients: A Cohort Study

Background: Cyclosporine A (CsA) is a cornerstone in graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic cell transplantation (allo-HCT), and a higher starting dose of 5 vs. 3 mg/kg reduces the risk of acute GVHD. Since hypertension is a relevant side effect of CsA, data on whether a higher CsA starting dose affects the incidence of hypertension are warranted. Methods: In this monocentric cohort study, 367 patients with no preexisting hypertension and treated with a CsA-containing GVHD prophylaxis were included: 230 (63%) with a CsA starting dose of 3 mg/kg and 137 (37%) with 5 mg/kg. The primary outcome was the incidence of early new-onset hypertension during the engraftment period. Potential risk factors for early new-onset hypertension were assessed using uni- and multivariable Cox regression models. Results: Overall, the cumulative incidence of early new-onset hypertension was 67% (246/367), but the incidence rate for early new-onset hypertension in the higher CsA group was lower (CsA 5 vs. 3 mg/kg: 57 vs. 67 per 1,000 patient-days; p = 0.414). In the multivariable analysis, risk factors for early new-onset hypertension were advanced patient age, obesity and prior autologous HCT, while a higher CsA starting dose was not associated with increased early new-onset hypertension (adjusted hazard ratio, 0.90; 95% CI, 0.67–1.21). Conclusions: A higher CSA starting dose of 5 vs. 3 mg/kg did not increase the risk of hypertension. Since previous analyses demonstrated a reduction in GVHD with a higher CsA starting dose of 5 mg/kg, current findings further support the safety of a higher CsA starting dose.