Increasing mixed chimerism and the risk of graft loss in children undergoing allogeneic hematopoietic stem cell transplantation for non-malignant disorders

Abstract

We performed quantitative PCR-based serial chimerism testing of whole blood (WB) and CD3 þ cells and retrospectively correlated the results of chimerism tests and the risk of graft loss in children undergoing transplant for non-malignant disorders. Twenty-four children were included in this study. All patients initially engrafted; subsequently, 12% lost the graft, 21% achieved complete donor chimerism and 67% had mixed chimerism (MC). Patients underwent delayed taper of cyclosporine (CsA) if they had MC. Overall survival was 87 ± 7% (s.d.) at 5-years post transplant, and it was not affected by chimerism status. Both WB and CD3 þ chimerism showed significant fluctuations with a peak in autologous cell signal occurring at a median of 7 months for WB and 2 months for CD3 þ cells. Initial post transplant chimerism percentage in either WB or CD3 þ lineage was not related to graft loss. Increasing MC to 430% host cells was seen in 33% of patients, and it was related to increased risk of graft loss, as previously published. However, 63% of children with increasing MC did not lose their graft. Additional studies of post transplant chimerism are required to improve our ability to accurately identify children at risk of graft loss following transplant for non-malignant disorders.

Haploidentical related-donor hematopoietic cell transplantation in children using megadoses of CliniMACs-selected CD34+ cells and a fixed CD3+ dose

“…We determined that a sample size of 21 patients was required to estimate the 95% confidence interval (CI) of the engraftment rate based on binomial approximations with the lower bound of 65.5%, and we closed the trial once that sample size was accrued. Donor engraftment was measured by analysis of short tandem repeats, as described previously, 13 beginning approximately 1 month post HCT and continuing monthly for the first year. The 2-year EFS, OS and relapse incidence (RI) were estimated by the Kaplan-Meier method using log-rank tests (SPSS 16.0, Chicago, IL, USA).…”

Early recipient chimerism testing in the T- and NK-cell lineages for risk assessment of graft rejection in pediatric patients undergoing allogeneic stem cell transplantation

“…6 Although the methods of chimerism testing are well established and its importance for graft monitoring is widely accepted, there is still considerable controversy regarding the actual relevance of distinct levels of recipient chimerism (RC) and its dynamics for graft outcome. [7][8][9][10][11][12] It is conceivable that the predictive value of chimerism levels might vary significantly depending on the underlying disease, the preparative regimen, the donor/recipient constellation and post-transplant immunosuppression.…”

Reduced-intensity conditioning hematopoietic SCT for pediatric patients with LAD-1: clinical efficacy and importance of chimerism

“…16,17 Mixed chimerism is defined by detection of 5-95% donor's HSC, in the recipient's BM or peripheral blood; full chimerism is quantified when 495% donor's HSC is detected in recipient's BM or peripheral blood. [18][19][20] Neutrophil engraftment is defined when ANC is 500/mL or greater on 3 consecutive days. Platelet engraftment is defined when the platelet count exceeded 20 Â 10 3 /mL for 3 consecutive days unsupported by platelet transfusion.…”