Clinical impact of NK-cell reconstitution after reduced intensity conditioned unrelated cord blood transplantation in patients with acute myeloid leukemia: analysis of a prospective phase II multicenter trial on behalf of the Société Française de Greffe de Moelle Osseuse et Thérapie Cellulaire and Eurocord

Abstract

Unrelated cord blood transplantation (UCBT) after a reduced intensity conditioning regimen (RIC) has extended the use of UCB in elderly patients and those with co-morbidities without an HLA-identical donor, although post-transplant relapse remains a concern in high-risk acute myeloid leukemia (AML) patients. HLA incompatibilities between donor and recipient might enhance the alloreactivity of natural killer (NK) cells after allogeneic hematopoietic stem-cell transplantation (HSCT). We studied the reconstitution of NK cells and KIR-L mismatch in 54 patients who underwent a RIC-UCBT for AML in CR in a prospective phase II clinical trial. After RIC-UCBT, NK cells displayed phenotypic features of both activation and immaturity. Restoration of their polyfunctional capacities depended on the timing of their acquisition of phenotypic markers of maturity. The incidence of treatment-related mortality (TRM) was correlated with low CD16 expression (P=0.043) and high HLA-DR expression (P=0.0008), whereas overall survival was associated with increased frequency of NK-cell degranulation (P=0.001). These features reflect a general impairment of the NK licensing process in HLA-mismatched HSCT and may aid the development of future strategies for selecting optimal UCB units and enhancing immune recovery.

Impact of graft sources on immune reconstitution and survival outcomes following allogeneic stem cell transplantation

“…Their activation occurs both by producing interferon-g and by cytotoxic activity, which are especially enriched in UCB grafts. 8,[24][25][26][27] Some studies have reported the potential kinetics of differentiated NK cells with respect to posttransplantation outcomes, especially during relapse, 24,28,29 GVHD, and NRM. 15,24,27,28 In contrast, CD20 1 B cells are well-known as mature B cells that are activated after allogeneic HSCT and show expansion in CBT.…”

Robust CD4+ T-cell recovery in adults transplanted with cord blood and no antithymocyte globulin

“…Our study could have benefited from an even larger patient sample size and more frequent lymphocyte subset immunophenotyping assessments. In addition, detailed evaluation of thymopoiesis, including T-cell receptor excision circles 15 and T-cell repertoire diversity, 43,46 virus-specific T-cell responses, 29,39,[48][49][50] and analysis of phenotypic or functional NK-cell reconstitution, 62,70,71 were not routinely performed. These should be investigated in the future to further elucidate the biology of immune recovery after CBT.…”

Clinical Relevance of Immunobiology in Umbilical Cord Blood Transplantation

“…The time to NK cell reconstitution (>0.1 × 10 9 /L) was similar between UCBT (1 month) and unrelated BMT (1.4 months), when both groups received ATG as part of the conditioning regimen [30]. Notably, after UCB with no ATG in the conditioning regimen, NK cell count reconstitution at 1 month after UCBT was similar to healthy controls [49,50]. Moreover, a better NK cell reconstitution with higher NK cell counts was observed over a 24-month period in UCBT than PBSCT [31,51].…”