Low-dose donor memory T-cell infusion after TCR alpha/beta depleted unrelated and haploidentical transplantation: results of a pilot trial

Abstract

Recovery of immunity is delayed in recipients of T-depleted grafts. Adoptive transfer of memory T-cells may improve immune response to common pathogens. A cohort of 53 patients with malignant (n = 36) and non-malignant conditions (n = 17) received TCR alpha/beta depleted grafts from haploidentical (n = 25) or MUD (n = 28) donors. Donor lymphocytes were depleted of CD45RA-positive cells. At a median of 48 days after transplantation, patients received DLI at 25 × 10/kg CD3 cells from haploidentical or 100 × 10/kg CD3 from MUD donors. Up to 3 doses of donor lymphocytes were administered at monthly intervals, escalating to 100 × 10/kg in haploidentical transplants and 300 × 10/kg in MUD transplants. At a median follow-up of 23 months, the cumulative incidence of de novo acute GVHD after DLI is 2% (1 of 43), while the rate of reactivation of preexisting aGVHD was 50% (5 of 10). The transplant-related mortality is 6%. The overall survival rates are 80% and 88% in malignant and non-malignant conditions, respectively. Among patients with absent CMV-specific immune reactivity at baseline (n = 31) expansion of CMV-specific T-cells was demonstrated in 20 (64.5%) within 100 days. Infusions of low dose donor memory T-lymphocytes are safe and constitute a simple measure to prevent infections in the setting of alpha/beta T cell-depleted transplantation.

αβ-T-cell-depleted haploidentical hematopoietic stem cell transplantation in children with chemorefractory acute myeloid leukemia

“…Семь пациентов получили в среднем по 3 (от 1 до 6) инфузии αβ-деплетированных Т-клеток; медиана времени до проведения терапии -44 (от 39 до 64) дня, среднее количество NK-клеток в продукте -10 × 10 6 /кг. С 2014 года часть пациентов получила инфузию CD45RA-деплетированных лимфоцитов в рамках пилотного исследования, результаты которого опубликованы ранее [13].…”

Haploidentical transplantation in high‐risk pediatric leukemia: A retrospective comparative analysis on behalf of the Spanish working Group for bone marrow transplantation in children (GETMON) and the Spanish Grupo for hematopoietic transplantation (GETH)

“…The choice is based on each center's experience. Research has focused on solving the issue of delayed immune reconstitution, mostly through adoptive transfer of non‐alloreactive T cells, either genetically modified or specifically selected …”

Selective T cell‐depleted haploidentical hematopoietic stem cell transplantation for relapsed/refractory neuroblastoma

“…Engraftment occurred at median of Day+11, and acute GvHD (Grade III/IV) was observed in 3 patients; only 3 patients had CMV viremia, and 1 had adenovirus cystitis despite the heavy pretreatment. Graft manipulation with TCRαβ/CD45RA depletion in our most recent patient combined the strength of TCRαβ/CD19 depletion and CD3/CD45RA depletion and is analogous to the recently reported strategy of HSCT with TCRαβ‐depleted graft followed by CD45RA‐depleted DLI . We offer initial data in the use of CD45RA‐depleted haploidentical grafts for patients with advanced NB.…”

“…The use of TCRαβ depletion allows preservation of TCRϒδ T cells, whereas CD45RA depletion conserves memory T cells, both of which possess antitumor effect without causing GvHD and facilitates engraftment . The presence of memory T cells also contributes to early quantitative and functional immune reconstitution.…”