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 stem cell transplantation (HSCT) induces a systemic autoimmune syndrome mimicking graft-vs.-host disease (GVHD). This syndrome, termed autologous GVHD has notable anti-tumour activity in animal studies. We intended to induce autologous GVHD with CyA in patients undergoing an autologous HSCT. We prospectively studied 118 patients with miscellaneous malignancies undergoing an autologous HSCT with low-dose CyA to characterize the clinical syndrome, its frequency and clinical course, and to determine the factors affecting its incidence. Patients received CyA from d -1 through to d 28, first starting at 2 mg/kg intravenously and then orally as soon as feasible. The dose was adjusted to achieve pre-dose blood levels around 100 ng/ml. A skin biopsy 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 irradiation (TBI) or high-dose cyclophosphamide were previously thought to be needed, autologous GVHD occurred in five out of 12 patients (42%) after a preparative regimen with high-dose melphalan alone. Autologous GVHD was significantly 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 with lymphoid malignancies or solid tumours. A significant negative association was also found with HLA-DR6. In lymphoma patients, GVHD occurred more frequently in advanced disease than in first or second complete remission (CR1-2) 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 analysis, there was no survival advantage for patients with GVHD. Phase III trials with this approach are needed to evaluate its anti-tumoral effect.
Baron
F
F
Department of Medicine, Division of Haematology, University of Liège, Liège, Belgium.
Gothot
A
A
Salmon
J P
JP
Hermanne
J P
JP
Pierard
G E
GE
Fillet
G
G
Beguin
Y
Y
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000601:surgery; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D015235:HLA-B Antigens / Q000276:immunology; D015808:HLA-DR6 Antigen / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000188:drug therapy / Q000276:immunology / Q000601:surgery; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007938:Leukemia / Q000188:drug therapy / Q000276:immunology / Q000601:surgery*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000276:immunology / Q000601:surgery; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000276:immunology / Q000601:surgery; D008223:Lymphoma / Q000188:drug therapy / Q000276:immunology / Q000601:surgery*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000276:immunology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000276:immunology / Q000601:surgery; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000276:immunology / Q000601:surgery; D011446:Prospective Studies; D014182:Transplantation, Autologous
D015235:HLA-B Antigens; C049278:HLA-B16 antigen; D015808:HLA-DR6 Antigen; D007166:Immunosuppressive Agents; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016572:Cyclosporine