Mixed chimerism after allogeneic hematopoietic stem cell transplantation for severe aplastic anemia

Abstract

Background: Mixed chimerism (MC) frequently occurs in patients with severe aplastic anemia (SAA) after allogeneic hematological stem cell transplantation (allo-HSCT). Methods: A retrospective study on 287 patients with SAA who underwent allo-HSCT between October 2012 and January 2020 was conducted to explore the outcomes, risk factors and treatment options for MC. Among 287 AA patients who excluded Fanconi anemia (FA), Congenital dyskeratosis (DKC), Paroxysmal nocturnal hemoglobinuria (PNH), etc.112 underwent matched sibling donor (MSD)-HSCT, 91 matched unrelated donor-HSCT and 84 haploidentical-HSCT. Patients were divided into the following 4 groups: group 1: Donor chimerism (DC); group 2: MC without cytopenia; group 3: MC with cytopenia; group 4: secondary graft failure (SGF). Results: Compared with the other three groups, SGF predicted a poor prognosis of SAA (P< 0.001). In addition, SGF was associated with the early (within 3 months after transplantation) presence of MC and the high levels of MC. Uni-and multivariate logistic regression analysis showed that donor/recipient sex-mismatching and CTX + ATG regimen were high-risk factors for MC. Of note, in MC patients with cytopenia (group 3), the effective response rate reached 55% (6/11) following enhanced immunosuppression combined with cellular therapy, while only one of the four was effective who received enhanced immunosuppression alone. Conclusion: SGF was associated with poor prognosis, early presence of MC and increased levels of recipient chimerism. The donor/recipient sex-mismatching and CTX + ATG regimen based MSD-HSCT were risk factors for MC. Cellular therapy could improve the effective response rate of patients with progressive MC.

Comparable long-term outcomes between upfront haploidentical and identical sibling donor transplant in aplastic anemia: a national registry-based study

“…Our findings underline that ISD SCT was associated with a higher incidence of mixed chimerism (18.7% vs. 2.8%), in line with results reported previously. 14 , 25 The results suggest that more intensive regimens might be attempted in ISD-SCT. For the recovery of routine blood tests in HID or ISD SCT, more than 95% of patients achieved normal complete blood counts at the final follow-up.…”

Mixed chimaerism is associated with poorer long-term failure-free survival among aplastic anaemia patients receiving HLA-matched donor transplantation

“…In our current analysis, we found that patient age and pre-SCT ferritin level were predictive adverse factors for the occurrence of mixed chimaerism among SAA patients who received HLA-matched donor transplantation. The association of patient age with mixed chimaerism has not been described in these studies [8][9][10][11] , which included not only HLA-matched transplants. In addition, the predictive role of pre-SCT ferritin was inconsistent with previously published literature.…”

“…On the other hand, an increasing number of studies have indicated that mixed chimaerism is an unsettling status that leads to cytopenia or graft rejection in SAA patients [9][10][11] . Regarding the effect of MC on overall survival outcomes, the reported studies have demonstrated con icting conclusions.…”

Mixed chimaerism is associated with poorer long-term failure-free survival among aplastic anaemia patients receiving HLA-matched donor transplantation

“…The reported incidence of mixed chimaerism ranges from approximately 20%-60% and varies among different conditioning regimens in HLA-matched donor transplantation for treating SAA 9,11,12,14 . Hill et al published their experience with Cy (200 mg/kg total) conditioning for MRD HSCT in 96 patients with SAA and demonstrated that a majority (58.3%) of the patients had evidence of mixed chimaerism post MRD SCT 12 .…”