Early T cell reconstitution and cytokine profile may help to guide a personalized management of human cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation

Human cytomegalovirus (HCMV) infection is one of the major causes of mortality and morbidity after allo-hematopoietic stem cell transplantation (HSCT). Antiviral therapies are associated with toxicity and high economic burden. The aim of this retrospective study was to identify allo-HSCT HCMV-seropositive recipients at low risk of clinically significant HCMV infection who could avoid antiviral therapies. Sixty adult patients who underwent allo-HSCT were clustered in two groups: i) 22 (37%) spontaneously controlling HCMV reactivation (Controllers); ii) 38 (63%) developing clinically significant HCMV infection and receiving pre-emptive therapy (Non-Controllers). We analyzed several patient baseline characteristics, total/HCMV-specific CD4(+) and CD8(+) T-cell counts and their cytokine production (IFN gamma, TNF alpha, IL2). Controllers presented a higher number of total/HCMV-specific CD4(+) and CD8(+) T-cells (P=0.001 and P=0.017 for total CD4(+) and CD8(+) T-cells respectively; P<0.001 for HCMV-specific T-cells) and a lower percentage of mono-functional IFN gamma-producing HCMV-specific CD8(+) T-cells (P=0.002). In bi-variable models, the prognostic impact of the percentage of mono-functional HCMV-specific CD8(+) T-cells on treatment-free survival, adjusted for total/HCMVspecific CD4(+) and CD8(+) T-cells, was confirmed. An HCMV-seronegative donor was the only baseline characteristic associated with a clinically significant infection. These data, when confirmed by a larger prospective study, may provide information for guiding the personalized management of HCMV infection in allo-HSCT recipients.

Automated summary

This retrospective study found that HSCT recipients who spontaneously controlled HCMV reactivation had higher CD4(+) and CD8(+) T-cell counts and lower percentage of HCMV-specific T-cells. The only baseline characteristic associated with clinically significant infection was an HCMV-seronegative donor.