Autologous peripheral blood stem cell transplantation with induction of autologous graft-versus-host disease in acute myeloid leukemia

Abstract

Summary:We studied whether the induction of autologous graftversus-host disease (GVHD) has an antileukemic effect and consequently increases the survival of patients undergoing autologous peripheral blood stem cell transplantation (PBSCT). In all, 22 acute myeloid leukemia patients with favorable and intermediate cytogenetic risk, in their first complete remission, were administered cyclosporine c.i.v. from day 0 to day þ 28 at a dose of 3.0 mg/kg per day and interferon-c (IFN-c) at 0.025 mg/m 2 s.c. every other day from day þ 14 to day þ 42 following autologous PBSCT. Natural-killer (NK)-cell activity assays and skin biopsies were performed. Successful engraftment was achieved in all patients at a median of 13 days without significant additional toxicity. Histologically confirmed cutaneous GVHD developed in 12 patients, and NK-cell activity was significantly augmented after autologous PBSCT in those patients (P ¼ 0.03). After a median follow-up duration of 37.7 months (range, 7.3-72.8), the 3-year disease-free survival (DFS) and overall survival (OS) rates were 64.4 and 73.1%, respectively, without significant correlation with GVHD status or augmentation of NK-cell activity. These data suggest that the administration of cyclosporine and IFN-c following autologous PBSCT improves OS and DFS, which may be attributable to the antileukemic effect, although no difference in survival could be demonstrated between cutaneous GVHD-positive and -negative groups. Bone Marrow Transplantation (2003) 32, 889-895. doi:10.1038/sj.bmt.1704251 Keywords: autologous GVHD; autologous stem cell transplantation; interferon-g; cyclosporine; natural-killercell activity; acute myeloid leukemia Clinically beneficial antitumor effects of graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation (BMT) have been reported previously, despite the fact that GVHD is associated with increased morbidity and mortality.1 Unfortunately, only 25% of patients have a suitable donor for allogeneic BMT and the remaining patients are eligible only for autologous stem cell transplantation (SCT) or unrelated-donor BMT. Although unrelated or mismatched-related BMT are associated with potent antitumor effects, many patients still lack a suitable donor or are not suitable candidates. The lack of a graftversus-tumor effect associated with GVHD may at least partly account for the higher relapse rate in autologous SCT patients. 2On the basis of findings that the relapse rate after allogeneic SCT is remarkably lower in patients with GVHD compared with patients who do not develop this syndrome, 1,3,4 the induction of autologous GVHD is one potential approach with which to improve the outcome for autologous SCT. Autologous GVHD can be induced by the administration of cyclosporine A (CsA) for a short period following autologous SCT. [5][6][7] This autoaggression syndrome shares a similar cutaneous pathology with acute GVHD after allogeneic SCT, even though autologous GVHD is milder, involves only the skin, and is self-limiting. Several initial ...

Autologous graft-versus-host disease: harnessing anti-tumor immunity through impaired self-tolerance

“…Park et al 23 examined CsA and IFN-g as post transplant immunotherapy in 22 first complete remission AML patients with favorable or intermediate-risk cytogenetic features. They administered myeloablative conditioning, followed by infusion of peripheral blood stem cells.…”

“…Phase I and II studies were performed to evaluate the potential efficacy of post transplant immune modulation using CsA with or without IFN-g to induce auto-GVHD. 10,14,[21][22][23][24][25][26] We will review these data from a clinical and mechanistic perspective and speculate as to how auto-GVHD might be more effectively harnessed in future clinical trials.…”