‘GVHD’: graft-versus-host disease or graft-versus-Hodgkin's disease? an old acronym with new meaning

Abstract

Summary:The majority of patients with relapsed or refractory Hodgkin's lymphoma (HL) will not be cured with standard therapy. Relapse rates remain high even after autologous stem cell transplantation (SCT), particularly for patients with high-risk disease. Allogeneic SCT offers several potential advantages for patients with HL. It is feasible when autologous stem cells are not available and stem cell grafts will be tumor free. Perhaps a more important advantage is the potential to generate a graftversus-Hodgkin's lymphoma (GVHL) effect. Unfortunately, although allogeneic SCT may cure some HL patients, treatment-related mortality has been unusually high, and superior survival, when compared to autologous SCT, has not been demonstrated. Nonmyeloablative conditioning and allogeneic SCT may induce a direct GVHL reaction with less conditioning regimen-related toxicity and ultimately may have the potential to improve cure rates and survival for advanced HL patients. The success of allogeneic SCT in many cases is related not just to the intensive conditioning regimen, but also to the antitumor properties of the donor graft. This graft-versustumor (GVT) effect is independent of the high-dose conditioning therapy, and is mediated, at least in part, by donor T cells contained in the stem cell graft. In fact, the rationale for some of the first clinical attempts at SCT was based on the potential of allogeneic bone marrow to provide 'adoptive immunotherapy' and destroy leukemia cells surviving radiation therapy. The contribution of a GVT response has been studied extensively and is clearly documented in animal models of SCT.2-5 Over the past decade, evidence has also accumulated for a potent GVT effect in human SCT. Initial evidence was based on several indirect although important clinical observations that included: (1) the abrupt withdrawal of immunosuppression (or a flare of acute graft-versus-hostdisease (GVHD)) re-established complete remission in some patients with relapsed acute leukemia; 6,7 (2) the risk of leukemic relapse was higher for recipients of syngeneic marrow grafts than for recipients of allogeneic grafts; 8,9 (3) GVHD after allogeneic bone marrow transplantation (BMT) was protective against relapse in some patient groups; 8,10 and (4) T-cell depletion of an allogeneic donor graft resulted in an increased relapse risk, especially for patients with chronic myelogenous leukemia (CML). 8,11 However, the use of donor leukocyte infusions (DLI) to treat relapse after allogeneic SCT provides the most direct evidence for a GVT reaction in humans. A total of 60-80% of patients with relapsed CML will achieve a complete molecular remission after infusion of unmanipulated donor leukocytes.12-17 The majority of DLI-induced remissions for CML are durable, and event-free survival rates are over 60-70%. 18-20GVT activity is disease specific Unfortunately, not all patients develop a GVT effect after DLI. Responses are disease specific and results from various studies are shown in Table 1. Response rates for patients with ...

Superiority of reduced-intensity allogeneic transplantation over conventional treatment for relapse of Hodgkin's lymphoma following autologous stem cell transplantation

“…Early studies of myeloablative transplantation provided some evidence suggesting the existence of such an effect, and encouraging data are now emerging from RIT studies, with small numbers of patients receiving DLI for disease relapse following transplant. 17,18 The durability of the few responses seen remains unclear, with the largest of these series reporting responses in four of nine patients with median follow-up of only 7 months. 18 We previously reported responses to DLI in eight of fifteen patients included in the current analysis (seven complete, one partial).…”

Fludarabine-melphalan as a preparative regimen for reduced-intensity conditioning allogeneic stem cell transplantation in relapsed and refractory Hodgkin's lymphoma: the updated M.D. Anderson Cancer Center experience

“…35 This report does not allow any final conclusions to be drawn on this issue because of its small sample size and its limited statistical power to detect such an effect. Acute and chronic GVHD had no measurable impact on PD.…”

Therapies for Relapsed Hodgkin Lymphoma: Transplant and Non-Transplant Approaches Including Immunotherapy

“…27 Reports of responses to DLI following disease relapse or progression, and decreased relapse rates in patients with either acute or chronic GVHD also substantiate a GVL effect in HL. 34,36,37 Radiotherapy Historical data confirm that there are occasional patients where RT alone for a limited relapse results in a long-term remission. Because previous series were small and subject to selection bias, the overall benefit and applicability of this approach are hard to define.…”