Clinical course and predictive factors for cyclosporin-induced autologous graft-versus-host disease after autologous haematopoietic stem cell transplantation

The administration of cyclosporin A (CyA) after autologous haematopoietic s tem cell transplantation (HSCT) induces a systemic autoimmune syndrome mimi cking graft-vs.-host disease (GVHD). This syndrome, termed autologous GVHD has notable anti-tumour activity in animal studies. We intended to induce a utologous GVHD with CyA in patients undergoing an autologous HSCT. We prosp ectively studied 118 patients with miscellaneous malignancies undergoing an autologous HSCT with low-dose CyA to characterize the clinical syndrome, i ts frequency and clinical course, and to determine the factors affecting it s incidence. Patients received CyA from d - 1 through to d 28, first starti ng at 2 mg/kg intravenously and then orally as soon as feasible. The dose w as adjusted to achieve pre-dose blood levels around 100 ng/ml. A skin biops y was performed when a skin rash was observed. Thirty-three percent of the patients developed clinical GVHD: clinical stage 1 in 21 patients, stage 2 in seven patients, and stage 3 in three patients. Although total body irrad iation (TBI) or high-dose cyclophosphamide were previously thought to be ne eded, autologous GVHD occurred in five out of 12 patients (42%) after a pre parative regimen with high-dose melphalan alone. Autologous GVHD was signif icantly more frequent in patients older than 33 years, in patients who had received high doses of granulocyte-macrophage colony forming units (CFU-GM) and in those with a diagnosis of myeloid malignancy, compared with those w ith lymphoid malignancies or solid tumours. A significant negative associat ion was also found with HLA-DR6. In lymphoma patients, GVHD occurred more f requently in advanced disease than in first or second complete remission (C R1-2) patients. All other factors studied were not predictive for GVHD. In conclusion, CyA-induced GVHD is reproducibly and safely induced with doses of CyA adapted to achieve blood levels around 100 ng/ml. In retrospective a nalysis, there was no survival advantage for patients with GVHD. Phase III trials with this approach are needed to evaluate its anti-tumoral effect.