Enhanced immune reconstitution of γδ T cells after allograft overcomes negative impact of pre-transplant MRD positive status in AML patients.: γδ T cells and MRD+ AML.

Klyuchnikov, Evgeny; Badbaran, Anita; Massoud, Radwan; Fritsche-Friedland, Ulrike; Janson, Dietlinde; Ayuk, Francis; Wolschke, Christine; Bacher, Vera; Kröger, Nicolaus (2021). Enhanced immune reconstitution of γδ T cells after allograft overcomes negative impact of pre-transplant MRD positive status in AML patients.: γδ T cells and MRD+ AML. Transplantation and cellular therapy, 27(10), pp. 841-850. Elsevier 10.1016/j.jtct.2021.06.003

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BACKGROUND

Minimal residual disease (MRD) prior to allogeneic stem cell transplantation (allo-SCT) in AML is a poor risk factor for outcome. The γδ T cells represents a unique minority lymphocyte population which is preferentially located in peripheral tissues, can recognize antigens in non-MHC restricted manner and plays a "bridging" role between innate and adaptive immune system.

OBJECTIVES

In this study, we investigated a potential graft-vs-leukaemia effect of γδ T cells reconstitution post-transplant in AML patients with pre-transplant positive minimal/measurable disease status (MRD+).

STUDY DESIGN

We investigated a potential graft-vs-leukaemia effect of γδ T cells reconstitution post-transplant in AML patients with pre-transplant positive MRD+. MRD assessment was performed in 202 patients (MRD+, n=100) with multicolored flow cytometry ("different from normal" strategy). Analysis for absolute concentrations of CD3+, CD4+, CD8+, NK, and γδ T cells were performed by flow cytometry according to an internal protocol at day +30 and +100 post-transplant. Differences between categorical and continuous variables were determined by Chi-square and Student's T-test, respectively. The Mann-Whitney test was used to compare medians of continuous variables. Spearman correlation was used for nonparametric assessment of correlation between different cell subsets during immune reconstitution. Kaplan Meier survival analysis and Cox regression analysis were used to investigate the associations between immune reconstitution and survival outcomes. Grays' analysis was used to compute incidences of relapses, non-relapse mortality (NRM) and graft-vs-host disease (GvHD).

RESULTS

Follow-up for survivors was 28 months (3-59). Younger age (≤58) of recipient and donor (<30), sex mismatch, matched donors, CMV reactivation and ATG were associated with a faster γδ T cell reconstitution. In multivariable analysis for MRD+ patients, higher than median level of γδ T cells on days +30 and +100 resulted in a significant improved leukaemia-free (HR 0.42, p=0.007 and HR 0.42, p=0.011, respectively) and overall survival (HR 0.44, p=0.038 and HR 0.33, p=0.009, respectively). Further, higher γδ T cell level on day +30 led to significant reduced risk of relapse (HR 0.36, p=0.019). No impact of γδ T cell level on day +30 and +100 could be seen in MRD- patients and no correlation with occurrence of graft-versus-host disease could be observed.

CONCLUSION

An enhanced immune reconstitution of γδ T cells post-transplant may overcome the higher relapse risk of pre-transplant MRD+ patients with AML.

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