According to a study published in Biology of Blood and Marrow Transplantation, treating patients who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) with sirolimus could be clinically relevant for preventing cytomegalovirus (CMV) infection. The results indicated that the risk of CMV DNAemia requiring preemptive treatment decreased by 6% per 1 ng/mL increase in sirolimus trough concentrations.
Sirolimus, a macrocyclic lactone, is an immunosuppressive drug used to prevent organ rejection after transplant and is known to protect against CMV infection in organ transplant, but its role in alloHSCT has remained controversial.
In this multicenter, retrospective study, researchers assessed sirolimus exposure and risk of developing first CMV DNAemia in 167 patients who underwent consecutive reduced-intensity conditioning (RIC) and alloHSCT and received sirolimus- and tacrolimus-based graft-versus-host-disease (GVHD) prophylaxis. CMV serostatus was positive for donors and/or recipients.
Patients had a median age of 59 years, and 60% were male. Median follow-up was 25 months (range, 4-85), and approximately 20% of patients had an HLA mismatch with the donor. A total of 73% of patients were allografted from an unrelated donor; in 31% (51 patients), the donor CMV serostatus was negative.
At a median of 56 days after stem cell infusion, 34% (56 patients) of recipients developed CMV DNAemia that required preemptive treatment, and the 2-year cumulative incidence was 36%. A Gompertz function, which is a sigmoid function that describes growth as slowest at the beginning and end of a given time period, best described time to CMV DNAemia requiring preemptive treatment.
Factors that predicted CMV DNAemia were antithymocytic globulin-based conditioning regimens (hazard ratio [HR] = 2.2, 95% confidence interval [CI], 1.1-4; P <.01) and concentration of sirolimus (HR = 0.94, 95% CI, 0.87-0.99; P <.01).
These results taken together with the risk of CMV DNAemia decreasing 6% per 1 ng/mL increase in trough concentrations of sirolimus indicate an association between serum concentration of sirolimus in patients who underwent alloHSCT and incidence of CMV DNAemia requiring preemptive treatment.
1. Guglieri-Lopez B, Perez-Pitarch A, Garcia-Cadenas I, et al. Effect of sirolimus exposure on the need for pre-emptive antiviral therapy for CMV infection after allogeneic hematopoietic stem cell transplantation [published online January 10, 2019]. Biol Blood Marrow Transplant. doi: 10.1016/j.bbmt.2019.01.012