Abstract

Leukemia relapse is the main cause for mortality after allogeneic stem cell transplantation (allo-SCT). Donor-derived allo-immune responses eliminate the residual host hematopoiesis and protect against relapse. Cytomegalovirus (CMV) reactivation (CMV-R) after allo-SCT may trigger anti-leukemic effects. The impact of CMV-specific CD8+ T-cells (CMV-CTLs) on the outcome after allo-SCT is currently unknown. Here, we studied the relationship between CMV-CTLs, overall T-cell reconstitution and relapse incidence in 103 patients with acute leukemia (n = 91) or myelodysplastic syndrome (n = 12) following CMV-seropositive recipient/donor (R+/D+) allo-SCT. Patients were subdivided based on the presence or absence of CMV-CTLs at 3 months after allo-SCT. Presence of CMV-CTLs was associated with preceding CMV-R and a fast T-cell reconstitution. Univariate analysis showed a significantly lower 1-, 2- and 5-year cumulative incidence of relapse (CIR) in patients with CMV-CTLs compared to those without CMV-CTLs. Multivariable regression analysis of the outcome performed with other relevant parameters chosen from univariate analysis revealed that presence of CMV-CTLs and chronic graft-versus-host disease (cGvHD) were the only independent factors associated with a low CIR. Onset of relapse was significantly later in patients with CMV-CTLs (median 489 days) than in in those without (median 152 days, p = 0.041) during a five-year follow-up. Presence of CMV-CTLs was associated with a lower incidence of early relapses (1 and 2-years), while cGvHD lead to a lower incidence of late relapses (2 to 5-years). In conclusion, our data show that CMV-CTLs indicate a functional immune-reconstitution protective against early relapse.

Highlights

  • Relapse is the main cause for mortality after allogeneic stem cell transplantation in patients with acute leukemia and myelodysplastic syndrome (MDS) [1]

  • Our study is the first to show that the presence of CMV-CTLs at 3 months after allo-SCT in patients with hematological malignancies transplanted in the CMV R+/D+ setting is associated with a reduction of early relapses

  • The present study focused on the impact of CMV-CTLs in comparison to other demographic and clinical parameters on the outcome selectively in acute leukemia and MDS patients after allo-SCT

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Summary

Introduction

Relapse is the main cause for mortality after allogeneic stem cell transplantation (allo-SCT) in patients with acute leukemia and myelodysplastic syndrome (MDS) [1]. We have shown recently that patients transplanted in the CMV R+/D+ setting after RIC have a faster overall T-cell reconstitution and lower host chimerism levels in the presence of CMV-CTLs at 3 months after allo-SCT [20].

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