Immunologic monitoring of cytomegalovirus for controlling clinically significant CMV infection in pediatric allogeneic hematopoietic stem cell transplant recipients

• Published in: PloS one 2021-02, Vol.16 (2), p.e0246191
• Main Authors: Seo, Euri, Choi, Eun Seok, Kim, Jung Hwa, Kim, Hyery, Koh, Kyung-Nam, Im, Ho Joon, Lee, Jina, Palaniyandi, Senthilnathan
• Format: Article
• Language: English
• Subjects: Children; Control; Cytomegalovirus infections; Diseases; Genetic aspects; Health aspects; Hematopoietic stem cells; Transplantation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0246191

The dynamics of recovery of cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) and its impact on controlling clinically significant CMV infections following hematopoietic stem cell transplant (HSCT) are rarely reported in pediatric HSCT recipients. In this study, dynamics of recovery of CMV-specific CMI and its clinical significance in controlling CMV viremia and clinically significant CMV infections were assessed in pediatric allogeneic HSCT recipients. All subjects underwent CMV pp65- and IE1-specific enzyme-linked immune absorbent spot (ELISPOT) assays just before transplantation and then monthly until the detection of CMV-specific CMI with [greater than or equal to] 5 spot-forming cells (SFC) / 2.0 x 10.sup.5 cells. Clinically significant CMV infections were defined as CMV diseases, prolonged CMV infections, recurrent CMV infections or late onset CMV infections. Among 52 recipients, 88.5% of recipients recovered CMV-specific CMI with [greater than or equal to] 5 SFC/ 2.0 x 10.sup.5 cells at a median of 34 days (interquartile range [IQR]: 29-95 days) following HSCT, 55.8% at 30 days following HSCT, and 73.1% at 90 days following HSCT. The presence of CMV-specific CMI before HSCT was the significant factors for the reconstitution of CMV specific CMI after HSCT (adjusted odds ratio [aOR] = 13.33; 95% confidence interval [CI] = 1.21-142.86). After HSCT, 30 recipients experienced CMV viremia, of which 20 were clinically significant CMV infections. The full recovery of CMV-specific CMI with [greater than or equal to] 50 SFC / 2.0 x 10.sup.5 cells after HSCT was the protective factor for the development of clinically significant CMV infections (aOR = 0.13; 95% CI = 0.22-0.71). In the haploidentical HSCT recipients, 82.1% recovered CMV-specific CMI at a median of 65 days after HSCT (IQR: 34-118 days) with a tendency to recover their CMV-specific CMI later than did those from non-haploidentical donors (65 days vs. 30 days; P = 0.001). Clinically significant CMV infections tended to occur more frequently in the haploidentical HSCT recipients compared to those with matched donor HSCT (46.4% vs. 29.2%; P = 0.205). The full recovery of CMV-specific CMI with [greater than or equal to] 50 SFC/2.0 x 10.sup.5 cells after HSCT also lowered the risk of development of clinically significant CMV infections (aOR = 0.08; 95% CI = 0.01-0.90). However, transplantation from haploidentical donors was a significant risk factor hampering recovery of CMV-specific CMI (aOR