Clinical implications of chimerism after allogeneic hematopoietic stem cell transplantation in children with non-malignant diseases

Abstract

BackgroundThe effects of chimerism on outcomes following allogeneic hematopoietic stem cell transplantation (HSCT) are unclear and may differ between diseases. We retrospectively evaluated the association between chimerism and transplant outcomes in children with nonmalignant diseases.MethodsChimerism was evaluated using short-tandem repeat polymerase chain reaction (STR-PCR) in 48 patients, with mixed chimerism (MC) defined as greater than 1% recipient cells.ResultsThe only variable exerting a significant influence on patients' chimerism status was the number of infused CD34+ cells. MC was detected in 23 transplants (9 showing transient MC; 10 with sustained low levels [≤30%] of autologous cells; and 4 with high-level MC [>30%]). The degree of STR-PCR at 28 days after HSCT was significantly higher in patients with high-level MC than those with transient or low-level MC. All patients with transient or low-level MC successfully maintained engraftment and showed a clinical response to HSCT, whereas 2 of the 4 patients with high-level MC experienced graft failure. The incidences of grades II-IV acute and chronic graft-versus-host disease (GVHD) were significantly higher in patients with complete donor chimerism (CC) than MC. We observed no significant survival differences between CC and MC groups. However, the survival rate was lower in patients with high MC than those with low-level or transient MC (P=0.03).ConclusionIn non-malignant diseases, MC may indicate a tolerant state with a decreased incidence of GVHD. However, high-level MC may signify an increased risk of graft failure and a lower survival rate.