Leukopenia With Mycophenolate in Calcineurin Inhibitor-Free, Corticosteroid-Free Renal Transplant Recipients.

Abstract

Leukopenia is common in corticosteroid (CS) free immunosuppressive (IS) regimens, possibly due to increased mycophenolic acid (MPA) exposure. This study evaluated the effect of MPA exposure on leukopenia and neutropenia in patients receiving belatacept (BELA) based regimens without calcineurin inhibitors or CS. Methods: The 0-12 hour area under the curve (AUC0-12h) of MPA was monitored in kidney-alone transplant recipients at 1 & 3 months post-transplant. Patients were on mycophenolate mofetil (MMF), CS-free, with either BELA (n=30) or tacrolimus (TAC; n=19) maintenance IS regimens. MPA exposure was estimated using a Bayesian estimator and a linear regression equation from Pawinski, et al (7.75 + 6.49C0 + 0.76C0.5 + 2.43C2). Target FK levels were 10-15ng/ml for the 1st month and 5-10ng/ml after. Leukopenia and neutropenia were defined as white blood cell count <3000cells/uL and absolute neutrophil count <1500cells/uL. Results: Risk of leukopenia and neutropenia increased with increased MPA AUC0-12h. An AUC0-12h>60ug*h/ml, calculated with Bayesian estimation, in BELA patients correlated with higher risk of neutropenia.Table: No Caption available.BELA patients with leukopenia or neutropenia >1 month post-transplant had a higher average 1st measured AUC0-12h than patients with neither (p=0.04).Figure: No Caption available.Similar results were not found in TAC patients, possibly due to insufficient sample size. The Bayesian and Pawinski methods provided comparable clinical guidance on when it may be appropriate to decrease MMF dose for AUC0-12h>60ug*h/ml in BELA and TAC patients (p=1). Conclusions: Risk of neutropenia increases with MPA AUC0-12h >60ug*h/ml in renal transplant patients on CS-free, BELA regimens. Elevated 1st measured MPA AUC0-12h predicts increased risk of adverse events >1 month in these patients. Estimates of MPA exposure by the Bayesian method agree with the Pawinski equation results in guiding clinical decisions for MMF dose changes.