Evaluation of Chimerism Dynamics after Allogeneic Hematopoietic Stem Cell Transplantation in Children with Nonmalignant Diseases

Maura Faraci, Francesca Bagnasco, Massimiliano Leoni, Stefano Giardino, Paola Terranova, Lorenzo Subissi, Marco Di Duca, Daniela Di Martino, Edoardo Lanino

It is recognized that chimerism following hematopoietic stem cell transplantation (HSCT) is a dynamic process. The aims of this study were to describe the evolution of chimerism in children with non-malignant diseases who underwent allogeneic HSCT, and to analyze the risk factors influencing chimerism status. 101 HSCTs were performed in 85 patients with non-malignant diseases. The donor was unrelated in 62.4% of HSCTs. Reduced intensity conditioning (RIC) regimen was administered in 48.5% of patients. Acute Graft-versus-Host Disease (a-GvHD) occurred in 51.7%, and chronic GvHD (c-GvHD) in 39.7% of patients. Analysis of chimerism was performed through amplification of nine specific short tandem repeats (STRs) by polymerase chain reaction (PCR) at engraftment and 1, 6 and 12 months after HSCT. Upon first evaluation, complete chimerism (CC) was detected in 34.7% and mixed chimerism (MC) in 55.4%, while graft failure occurred in 9.9% of patients. Severe a-GvHD was associated with CC (P=0.031). The last chimerism evaluation showed CC in 72.1%, stable mixed chimerism (SMC) in 12.8% and progressive mixed chimerism (PMC) in 3.5%. CC was associated with a higher incidence of a-GvHD (P=0.016) and c-GvHD (P=0.022), while the reduced-intensity conditioning regimen was associated with graft failure (P=0.026). One- and 3-year overall survival (OS) was 87.4% and 80.5% respectively, with a lower OS at 3 years in patients with CC compared to those with MC (P=0.008). Acute and chronic GvHD represent factors favoring CC, thus close, careful follow-up of chimerism is recommended in patients affected by non-malignant disease.