PREVENTION OF GRAFT-VERSUS-HOST-DISEASE WITH ANTI-CD5 RICIN-A CHAIN IMMUNOTOXIN AFTER CD3-DEPLETED HLA-NONIDENTICAL MARROW TRANSPLANTATION IN PEDIATRIC LEUKEMIA PATIENTS

To determine if partial T cell depletion and intensive post-transplant immunosuppression is effective for the prevention of graft-versus-hos t disease (GVHD) in pediatric recipients of HLA-non-identical marrow t ransplants, 10 children with leukemia received high-dose thiotepa, cyc lophosphamide and total body irradiation followed by transplantation o f CD3-depleted marrow from matched unrelated or one-antigen mismatched related adult donors. To maximize the number of stem cells infused, a large volume (1-1.51) of marrow was harvested from the donors. After immunopurging, the marrow infused contained a median of 3.7 x 10(6) CD 34(+) cells/kg, 1.4 x 10(6) CD3(+) cells/kg, and 1.6 x 10(6) CD5(+) ce lls/kg as assessed by flow cytometry. Cyclosporine, methylprednisolone and anti-CD4 ricin A chain immunotoxin (XZ-CD5) were used for prevent ion of GVHD post-transplant. All patients achieved an ANC > 0.5 x 10(9 )/l. No patient developed capillary leak syndrome or renal failure fro m XZ-CD5. Five developed grade 2-4 acute GVHD, and all responded to tr eatment with steroids. Five of nine evaluable patients developed chron ic GVHD. Two patients relapsed, but the most common cause of death was infection with or without chronic GVHD. Four patients survive 10+ to 27+ months post-transplant. XZ-CD5 is well-tolerated in T cell-deplete d marrow transplant recipients. However, partial T cell depletion and intensive post-transplant immunosuppression did not prevent moderate a cute GVHD or chronic GVHD. This may have been due to the high number o f T cells infused with the marrow.