The graft-versus-lymphoma effect: clinical review and future opportunities

Abstract

Summary:Numerous lines of preclinical and clinical evidence support the existence of a graft-versus-leukemia effect, but less evidence supporting a comparable graft-versus-lymphoma effect exists. We review here current clinical data addressing the graft-versus-lymphoma effect, including comparisons of autologous, syngeneic, and allogeneic transplantation; responses to immunomodulation; and responses to nonmyeloablative stem cell transplantation. Despite several limitations of the data, we believe that there is sufficient evidence suggesting a significant graftversus-lymphoma effect. In addition, we discuss approaches for clinical management of lymphoma patients, opportunities for mechanistic studies afforded by donor leukocyte infusions and nonmyeloablative transplantation, and suggestions for clinical studies to further define the magnitude and applicability of the graft-versus-lymphoma effect. For over two decades, scientists and clinicians have recognized the existence of a graft-versus-tumor effect, whose role has become increasingly important in the treatment of hematologic malignancies. Initially suggested by numerous animal studies and corroborated by considerable retrospective analysis of clinical data, this effect is most directly supported by durable responses to withdrawal of immunosuppression, administration of donor leukocytes, and more recently, nonmyeloablative stem cell transplantation. Most studies to date have investigated the graft-versusleukemia effect, while comparable studies of a graft-versuslymphoma effect have been limited. Current data regarding graft-versus-lymphoma activity, however, have increasingly supported the likelihood of its existence. We review below the most recent evidence, composed of case reports and small series, larger retrospective analyses, and few prospective studies, suggesting a graft-versus-lymphoma effect.

Allogeneic hematopoietic cell transplantation for diffuse large B cell lymphoma: who, when and how?

“…Differences in the intrinsic antigen-presenting ability of DLBCL cells as compared with indolent lymphomas may provide an explanation for a potentially weaker GVL effect in DLBCL. 48 In addition, the more aggressive growth kinetics of DLBCL (compared with follicular and mantle cell lymphoma) may outpace an effective GVL response in many cases. However, there are strategies that could be employed to enhance the GVL response.…”

Immunotherapy of recurrent B-cell malignancies after allo-SCT with Bi20 (FBTA05), a trifunctional anti-CD3 × anti-CD20 antibody and donor lymphocyte infusion

“…[2][3][4] In a retrospective data analysis of the International Bone Marrow Transplant Registry and European Group for Blood and Marrow Transplantation, allogeneic transplantation was not superior to syngeneic transplantation, indicating the absence of an allogeneic GVL effect. 5 However, several studies and observations report a GVL effect of donor lymphocyte infusions (DLIs).…”

Ibritumomab tiuxetan (Zevalin) combined with reduced-intensity conditioning and allogeneic stem-cell transplantation (SCT) in patients with chemorefractory non-Hodgkin's lymphoma

“…3 Allogeneic SCT offers a potentially curative option to patients with lymphoma by providing high-dose chemotherapy as well as a graft-versus-lymphoma (GVLy) effect. 4 Allogeneic SCT may be a therapeutic option for patients with chemo-refractory aggressive lymphoma and for patients failing a prior autologous SCT. It also may be offered as an option to cure patients with indolent lymphoma, where autologous SCT is not considered curative.…”