59 O - Thiotepa improves results of t-cell-depleted bone marrow tranplants for acute leukemia. a seven year experience

Abstract

T cell-depletion of the donor bone marrow prevents GvHD in matched BMT recipients, but this benefit is offset by an increased risk of graft failure and leukemia relapse. One approach 10 improving disease-free survival of TCD transplants recipients is to employ intensified conditioning regimens. More intensive pre-transplant immunosuppression and myeloablation should compensate for the loss of the anti-host and anti-leukemic effect, mediated by donor T cells and thereby overcome resistance to engraftment and provide a greater anti-leukemic activity. To this end, we desisned in 1989, a new conditioning regimen that added ATG and thiotepa (IT) to Cy and 1440 cGy hyperfractionated TBI, to enhance both immunosuppression and myeloablation. From June 1989, 54 patients (33 M, 21 F; median age 29 years, range 6–53) with acute leukemia (30 AML, 24 ALL) in hematological remission (22 CR L 14 CR II) or relapse (N = 18) received HLA-identical BMI depleted of T cells by the soybean agglutinin and E-rosetting technique. No additional post-transplant immunosuppressive treatment was given. All patients engrafted with a full-donor type chimerism. Neither acute nor chronic GvHD occurred in any evaluable patient of the 36 patients in remission at transplant, 24, survive event-tree at a median follow-up of 50 months (range 26.78) with a PS 100%. 6 relapsed (2AML, 4 ALL) and 6 died from TRM Of the 18 in relapse at transplant, 4 survive event-free at a median follow-up of 44 months (range 30–46), 7 relapsed (2AML.5ALL) and 6 died from TRM. We believe that TT enhances the cytoreductive elfect of the conventional conditioning regimens in T-depleted BMTs and that there is a GvL effect mediated by the expansion of immunocompetent lymphocytes in the absence of GvHD when no cyclosporine is given.