Abstract
Cyclosporine A (CsA) is commonly used for Graft versus Host Disease (GvHD) prophylaxis at a recommended starting dose of 3 mg/kg/d: Evidence for the effect of different CsA starting doses on GvHD risk is limited. We therefore estimated the association of 5 mg/kg/d (CsA5) and 3 mg/kg/d (CsA3) CsA starting doses with GvHD risk in two consecutive cohorts of allogeneic hematopoietic cell transplantation (allo-HCT) patients, exploring potential risk factors for incident acute GvHD, with a focus on CsA starting dose. We analyzed 519 patients within CsA5 (n = 153) and CsA3 (n = 366). The cumulative incidence function of acute GvHD grade ≥2 was higher in the CsA3 compared to the CsA5 group (41% vs. 33%, respectively; p = 0.043), without impacting chronic GvHD. In multivariable analysis, a CsA starting dose of 3 mg/kg/d, no ATG use, unrelated donor and high to very high disease risk index were significantly associated with acute GvHD grade ≥2. A higher CsA starting dose of 5 mg/kg/d was independently associated with lower acute GvHD risk, and higher CsA levels in the early period after allo-HCT were reached.
Highlights
Allogeneic hematopoietic cell transplantation offers a potential curative option for various hematological disorders [1,2,3], but is associated with significant morbidity and mortality [4, 5]
The Graft versus Host Disease (GvHD) is a frequent complication after allo-HCT with impact on morbidity and mortality [4, 5]
Continuous and detailed investigations to optimize GvHD prophylaxis are warranted [12, 13]. Calcineurin inhibitors such as CsA have been the backbone of GvHD prophylaxis for decades [20, 21]
Summary
Allogeneic hematopoietic cell transplantation (allo-HCT) offers a potential curative option for various hematological disorders [1,2,3], but is associated with significant morbidity and mortality [4, 5]. We could demonstrate that close monitoring of CsA dosing with active adjustments to maintain therapeutic CsA levels >195 μg/L in the first 10 days after allo-HCT significantly may reduce the incidence of aGvHD [36]. It is unclear if higher CsA starting doses affect post-allo-HCT CsA levels and GvHD risk [22, 27, 36, 37]. We report the potential impact of this measure on clinical outcomes
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