Transplantation of autologous and allogeneic bone marrow with liver from acadaveric donor for primary liver cancer

Background. In histocompatibility mismatched experimental animals, a combin ation of T-cell-depleted autologous and allogeneic marrow may induce mixed chimerism and tolerance. Patients with large primary Liver tumors have a po or outcome. We investigated whether it were possible to induce mixed chimer ism and obtain an antitumor effect in a patient with a large primary liver cancer after combined liver and bone marrow transplantation (BMT), Methods. A 46-year-old female with a primary non resectable liver cancer re ceived a liver transplant from a cadaveric donor. Subsequently, she was con ditioned with 4x2 Gy of total lymphoid irradiation, 120 mg/kg cyclophospham ide, and 7.5 Gy total body irradiation, Twelve days after liver transplanta tion, she received T-cell-depleted autologous: cadaveric 5/6 antigen HLA-mi smatched marrow in a proportion of CD34+ cells of 0.5 : 3.0x10(6)/kg, Chime rism status was determined with polymerase chain reaction amplification of variable number tandem repeats from DNA obtained from CD3+, CD19+, and CD45 + magnetic-bead-separated cells. Results. The early posttransplant period was uneventful; Liver function was normal and the hematopoietic engraftment of donor and recipient origin was prompt, alpha-fetoprotein levels dropped from 440 to 35 mu g/l. One month after marrow transplantation, donor T-cells decreased markedly. Monoclonal antibody OKT-3 and 10(5)/kg donor T-cells were given, One month later, the patient developed diarrhea and abdominal pain. A colonoscopy showed moderat e gastrointestinal acute graft-versus-host disease and a Cryptosporidium in fection. Three months after BRIT, she became a complete donor chimera, Chim era cells showed little, if any, reactivity in mixed lymphocyte cultures to recipient and donor cells, but reacted to third party, Five months after B RIT, she developed progressive Aspergillus fumigatus pneumonia and died, No tumor was found at the autopsy. Conclusion. We obtained mixed donor-recipient hematopoietic chimerism witho ut severe acute graft-versus-host-disease, after combined T-cell depleted a utologous and allogeneic BMT and a transplantation of a liver from an HLA-m ismatched cadaveric donor. Additional donor T-cells enhanced donor bone mar row engraftment, but rejected the autograft, On the basis of this first att empt, further clinical studies are warranted.