Novel CD62L depleted donor lymphocyte infusion with T-cell receptor alpha-beta depleted haploidentical hematopoietic stem cell transplantation in children

Abstract

Ex-vivo depletion of donor CD45RA+ naïve T-cells can reduce graft-versus-host-disease (GVHD) in haploidentical hematopoietic stem cell transplantation (HSCT) while providing memory T-cells to reduce infections. CD62L is another marker of naïve T-cells. Depletion of CD62L+ cells may offer advantages of removing central memory T-cells which may also cause mild GVHD, and retain CD45RA+ effector memory T-cells (TEMRA). We aimed to evaluate the depletion efficiency, safety and immunoreconstitution after novel CD62L depleted donor lymphocyte infusion (DLI) with T-cell receptor (TCR)-αβ depleted haploidentical HSCT. Children with malignant or non-malignant diseases who underwent the first TCRαβ depleted haploidentical HSCT were recruited to receive CD62L depleted DLI on day 0 at a dose of 1 × 10⁶/kg or 5 × 10⁶/kg CD3+CD62L- cells using the CliniMACS device. Six children aged 0.3–15 years received 4.6-10 × 10⁶/kg CD34+ cells. CD62L depletion resulted in undetectable CD3+CD62L+ cells in 4 patients and 3.39–3.52 log reduction in 2 patients. Infusion was well-tolerated. All patients had neutrophil and platelet engrafted early (medians 10 and 9.5 days respectively) with 100 % donor chimerism. Only one patient had grade 1 acute GVHD. None had chronic GVHD. Post-transplant recovery of CD3+ cells reached a median of 117/uL at 1 month and as high as 352/uL at 3 months. TEMRA cells were present at 1 month (median 2 cells/uL) and increased 3 months post-transplant (median 21 cells/uL). In conclusion, CD62L depletion is highly efficient and appears safe and does not affect engraftment. It provides TEMRA and effector memory T-cells to protect the recipient against infections. Risk of GVHD is low.