Monitoring Early CMV-Specific CD8+ T-Cell Responses After Allogeneic Stem Cell Transplantation By Pentamer and Streptamer Staining

Abstract

We present the results of a pilot study using pentamer (PM) and streptamer (ST) multimer complexes for monitoring CMV-specific CD8+ T-cells (CTLs). We analysed 15 patients that underwent allogeneic Stem Cell Transplantation (HSCT). Patient characteristics are summarized in Table 1. All patients and donors were positive for the HLA-A*02:01 allele. PM and ST were directed against the epitope NLVPMVATV (495-503) of the CMV phosphoprotein 65 (pp65). Samples were obtained at 15-day intervals until day +90 and monthly thereafter.PatientCMV status (D/R)GenderAgeDiagnosisDonorConditioningEngraftment (day)Follow up (months)GVHD (day)1+/+F43NHLSIBRIC2415-2-/+F33MDSURDRIC1912-3+/+M55AMLSIBMAC1714474-/+F41AMLURDMAC2121-5+/+F32AMLSIBMAC2013256+/+F64MDSSIBRIC2714897-/+M58CLLURDRIC2313928+/+M57ALLURDMAC155-9+/+F39AMLURDMAC2012-10-/+M42ALLURDMAC2125-11-/+M44AMLURDMAC12815312+/+F65AMLSIBRIC258-13-/+M27AMLSIBMAC3031814+/+M65AMLSIBRIC1966215+/-F30SAASIBRIC133- Three patterns were observed. In 3 patients (20%) no CMV-specific-CTLs could be detected despite several CMV reactivations, requiring prolonged cumulative antiviral therapy (median 68 days; range 67-136). In 7 patients (47%) CMV reactivation occurred at a mean of 41 days (10-94) and triggered a rapid increase of CMV-specific-CTLs with a median of 22.7 x 105/L (range 1.3-279.7). The CMV-PCR became immediately negative and antiviral therapy was stopped promptly after a median of 15.5 days (6-23). Finally, 5 patients (33%) showed an early immune reconstitution with CMV-specific-CTLs detected with a median of 0.7 x 105/L (range 0.2-2.8) in the absence of CMV-PCR reactivation at a median of 21 days (10-34) post-SCT. No CMV-PCR reactivation was observed in this group with a median follow-up of 12 months (5-14). Discussion Monitoring CMV-specific-T-cells might be able to distinguish patients at higher risk of recurrent virus reactivation and in need of prolonged antiviral therapy. Patients with increasing CMV-specific-CTLs detectable at the time of CMV-PCR reactivation may only need a short course of antiviral therapy, while those with early CMV-specific-CTLs may be protected from CMV reactivation. Conclusion Using Multimer-based (Pentamer and Streptamer) monitoring of CMV-specific T-cell immune reconstitution after allogeneic HSCT may contribute to the clinical decision regarding when and for how long to commence anti-CMV therapy. Disclosures: No relevant conflicts of interest to declare.