Data from Development of Tumor-Reactive T Cells After Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplant for Chronic Lymphocytic Leukemia

Abstract

<div>Abstract<p><b>Purpose:</b> Allogeneic nonmyeloablative hematopoietic stem cell transplant (NM-HSCT) can result in durable remission of chronic lymphocytic leukemia (CLL). It is thought that the efficacy of NM-HSCT is mediated by recognition of tumor cells by T cells in the donor stem cell graft. We evaluated the development of CTLs specific for CLL after NM-HSCT to determine if their presence correlated with antitumor efficacy.</p><p><b>Experimental Design:</b> Peripheral blood mononuclear cells obtained from 12 transplant recipients at intervals after NM-HSCT were stimulated <i>in vitro</i> with CLL cells. Polyclonal T-cell lines and CD8<sup>+</sup> T-cell clones were derived from these cultures and evaluated for lysis of donor and recipient target cells including CLL. The presence and specificity of responses was correlated with clinical outcomes.</p><p><b>Results:</b> Eight of the 12 patients achieved remission or a major antitumor response and all 8 developed CD8<sup>+</sup> and CD4<sup>+</sup> T cells specific for antigens expressed by CLL. A clonal analysis of the CD8<sup>+</sup> T-cell response identified T cells specific for multiple minor histocompatibility (H) antigens expressed on CLL in six of the responding patients. A significant fraction of the CD8<sup>+</sup> T-cell response in some patients was also directed against nonshared tumor-specific antigens. By contrast, CLL-reactive T cells were not detected in the four patients who had persistent CLL after NM-HSCT, despite the development of graft-versus-host disease.</p><p><b>Conclusions:</b> The development of a diverse T-cell response specific for minor H and tumor-associated antigens expressed by CLL predicts an effective graft-versus-leukemia response after NM-HSCT.</p></div>