Dynamics of cytomegalovirus‐specific T‐cell recovery in allogeneic hematopoietic cell transplant recipients using a commercially available flow cytometry assay: A pilot study

Abstract

AbstractBackgroundCytomegalovirus‐specific T‐cell‐mediated immunity (CMV‐CMI) protects from CMV infection in allogeneic hematopoietic cell transplantation (allo‐HCT), but to date, there is no validated measure of CMV immunity for this population.MethodsIn this prospective, observational, pilot study, CMV T‐cell responses were evaluated monthly and at onset of graft‐versus‐host disease (GVHD) or CMV infection in CMV‐seropositive allo‐HCT recipients using a commercial flow cytometry assay, the CMV inSIGHT T‐Cell Immunity Panel (CMV‐TCIP). The primary endpoint was the time to first positive CMV‐TCIP, defined as percentage of interferon‐γ‐producing CD4+ or CD8+ CMV‐specific T cells >0.2%. Letermovir was prescribed from day +10 to ≥100.ResultsTwenty‐eight allo‐HCT recipients were enrolled. The median time to first positive CMV‐TCIP result was earlier for CD4+ (60 days [interquartile range, IQR 33‒148]) than for CD8+ T cells (96 days [IQR 33‒155]) and longer for haploidentical and mismatched transplant recipients (77 and 96 days, respectively) than for matched donors (45 and 33 days, respectively). CD4+ and CD8+ CMV‐CMI recovery was sustained in 10/10 (100%) and 10/11 (91%) patients, respectively, without GVHD, whereas CD4+ and/or CD8+ CMV‐CMI was lost in 4/6 and 2/6 patients, respectively, with GVHD requiring steroids. As a predictor of clinically significant CMV infection in patients with low‐level CMV reactivation, the sensitivity and negative predictive value of CMV‐TCIP were 90% and 87.5%, respectively, for CD4+ CMV‐TCIP and 66.7% and 62.5%, respectively, for CD8+ CMV‐TCIP.ConclusionsThere was significant variability in time to CMV‐CMI recovery post‐HCT, with slower recovery after haploidentical and mismatched HCT. CD4+ CMV‐CMI may protect against CS‐CMVi, but immunity may be lost with GVHD diagnosis and treatment. image