Elfeky, R;
Shah, RM;
Unni, MN;
Ottaviano, G;
Rao, K;
Chiesa, R;
Amrolia, P;
... Veys, P; + view all
(2019)
New graft manipulation strategies improved outcome of mismatched stem cell transplantation in children with primary immunodeficiencies.
Journal of Allergy and Clinical Immunology
, 144
(1)
pp. 280-293.
10.1016/j.jaci.2019.01.030.
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Amrolia_New graft manipulation strategies improved outcome of mismatched stem cell transplantation in children with primary immunodeficiencies_AAM.pdf - Accepted Version Download (1MB) | Preview |
Abstract
BACKGROUND: Mismatched stem cell transplantation is associated with high risk of graft loss, graft versus host disease (GvHD) and transplant related mortality (TRM). Alternative graft manipulation strategies have been employed over the last 11 years to reduce these risks. OBJECTIVE: We investigated the outcome of using different graft manipulation strategies among children with primary immunodeficiency (PID). METHODS: Between 2006-2017, 147 PID patients received 155 mismatched grafts; 30 TCRαβ/CD19 depleted, 43 cords (72% with no serotherapy), 17 CD34+ selection with T cell add-back and 65 unmanipulated grafts. RESULTS: The estimated 8-year survival of the entire cohort was 79%, TRM was 21.7% and graft failure rate was 6.7%. Post-transplant viral reactivation, aGvHD grades II-IV and chronic GvHD complicated 49.6%, 35% and 15% transplants, respectively. The use of TCR αβ/CD19 depletion was associated with a significantly lower incidence of grade II-IV aGvHD (11.5%) and cGvHD (0%) however with a higher incidence of viral reactivation (70%) in comparison to other grafts. T cell immune reconstitution was robust among cord transplants however with a high incidence of aGvHD grade II-IV 56.7%. Stable full donor engraftment was significantly higher at 80% among TCRαβ+/CD19+depleted and cord transplants versus 40-60% among the other groups. CONCLUSIONS: Rapidly accessible cord and haploidentical grafts are suitable alternatives for patients with no HLA matched donor. Cord transplantation without serotherapy and TCRαβ+/CD19+depleted grafts produced comparable survival rates of around 80% albeit with a high rate of aGvHD with the former and high risk of viral reactivation with the latter that need to be addressed.
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