Low-dose donor memory T-cell infusion after TCR alpha/beta depleted unrelated and haploidentical transplantation: results of a pilot trial. (March 2018)

• Record Type: Journal Article
• Authors: Maschan, Michael; Blagov, Sergey; Shelikhova, Larisa; Shekhovtsova, Zhanna; Balashov, Dmitriy; Starichkova, Julia; Kurnikova, Elena; Boyakova, Elena; Muzalevskii, Yakov; Kazachenok, Alexei; Trakhtman, Pavel; Osipova, Elena; Khripkova, Natalia; Zhogov, Vladimir; Novichkova, Galina; Maschan, Alexei
• Is Part Of: Bone marrow transplantation. Volume 53:Number 3(2018)
• Page Start: 264
• Page End: 273
• Publication Date: 2018-03
• Subjects: Bone marrow -- Transplantation -- Periodicals; 617.4410592
• DOI: 10.1038/s41409-017-0035-y
• Languages: English
• ISSNs: 0268-3369

Abstract

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 × 103 /kg CD3 cells from haploidentical or 100 × 103 /kg CD3 from MUD donors. Up to 3 doses of donor lymphocytes were administered at monthly intervals, escalating to 100 × 103 /kg in haploidentical transplants and 300 × 103 /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.