Thymic Recovery among Pediatric Stem Cell Recipients.
Authors: Olkinuora Helena , Kaartinen Tanja , Siitonen Sanna , Talvensaari Kimmo , Pihkala Ulla , Vettenranta Kim 
Published: April 2020

BACKGROUND: Thymic recovery is an essential part of immune reconstitution post stem cell transplantation. The process is affected by the age of the recipient, use of radiotherapy in conditioning and graft versus host disease. The duration of impaired T cell function depends mainly on thymic recovery and is associated with an increased risk of complications such as infections. The aim of this study was to evaluate thymic recovery post-transplant in pediatric patients. And also to detect differencies in thymic recovery between recipients of autologous stem cell rescue and those of allogeneic grafts from sibling and unrelated donors

MATERIAL AND METHODS: Between 8/2001–8/2005 a total of 66 patients with a mean age of 7 yrs with either a malignant or non-malignant disease were studied. 31 received a matched unrelated, 21 a sibling graft and 14 were given autologous stem cell rescue. Thymic function was evaluated by quantifying TREC (T cell receptor excision circles) levels in peripheral blood mononuclear cells by real time quantitative PCR once prior to transplant and once every three months during the first year and at 18 months post-transplant. FOXP3 levels were evaluated simultaneously with those of TREC by real time quantitative PCR. The data was related to the clinical status of patients and the recovery of peripheral blood T cell numbers. In 29% (6/21) of the recipients of sibling grafts and 65% (20/31) of recipients of unrelated grafts had clinically significant (Gr II–IV) acute graft versus host disease. About 30 % in both groups developed chronic graft versus host disease.

RESULTS: Comparison of TREC levels in children following SCT indicated that thymic recovery was brisk among recipients of autologous stem cell rescue by the 6 months and within the allogeneic group the recovery was significantly better in recipients of sibling grafts than in recipients of unrelated grafts (Figure 1.0). There was an significant negative association between the values of TREC and the occurrence of chronic graft versus host disease from 6 months to 18 months post-transplant. Children with low (below median) TREC values had increased mortality. Patients with low TREC experienced more infections during first six months post-transplant than children with high (above median) TREC values. Blood numbers of CD4 naive cells (CD45RA+) and CD27+ cells correlated significantly with TREC values.

FOXP3 values were associated at three months post-transplant with acute graft versus host disease and with its chronic form at 12 and 18 months post-transplant. FOXP3 correlated with blood CD4 naive cells (CD45RA+) and CD27+ cells at 12 and 18 months post-transplant.

There was a significant correlation between levels of TREC and FOXP3 at 12 and 18 months post stem cell transplant.

CONCLUSIONS: Our data may indicate a difference in the kinetics of thymic recovery post-transplant between recipients of sibling and URD grafts and those of autologous stem cell rescue.

Chronic GVHD seems to associate with thymic dysfunction and herpesviral infections with the pace of thymic recovery.

Figure Figure