AUTOLOGOUS BONE-MARROW MIXED WITH HLA-HAPLOIDENTICAL ALLOGENEIC MARROW TRANSPLANTATION FOR TREATMENT OF PATIENTS WITH MALIGNANT BLOOD-DISEASES

We have previously demonstrated that syngeneic marrow mixed with H-2 h aploidentical marrow transplantation could provide not only protection against graft-versus-host disease (GVHD) but also anti-leukemic (GVL) effects in mice. In the present studies, we report clinical observati ons using autologous marrow mixed with HLA-haploidentical allogeneic m arrow transplantation for treatment of patients with malignant blood d iseases. Sixteen cases, including 12 with acute leukemia and four with advanced malignant lymphoma, were treated by autologous marrow, which was purged in vitro by hyperthermia (42.5 degrees C for 70 min) follo wing incubation for 5 days with interleukin 2 (IL-2) in liquid culture and mixed with HLA haploidentical marrow cells from their sibling or parent. Acute GVHD was not observed in any patient after transplantati on. Hematological rescue in the clinical setting was demonstrated in a ll cases but one who died early from hepatic venoocclusive disease (VO D). Five cases who were transplanted at the time of CR2 or CR3 and in advanced phase of lymphoma, relapsed 4 to 7 months after transplantati on. The relapse rate was 31.3%. None of eight patients who received al logeneic BMT within 2 h after ABMT relapsed wth median follow-up of 12 months and two of them died from procedure-related complications. Sev en cases are still alive and disease-free with a median follow-up of 1 2 months. Mixed chimerism was found in 3/6 cases, who had different se x donors, by analysis of sex chromosomes. These results show that mixe d transplantation is a safe, effective and new approach to treating pa tients with malignant tumors. In order to detect the effects of GVL, s tudies are now in progress in our clinic.