Adoptive immunotherapy with haploidentical allogeneic peripheral blood lymphocytes following autologous bone marrow transplantation

Objective. Patients who undergo autologous bone marrow transplantation for acute leukemia are at high risk for relapse, We have evaluated the feasibil ity of administering cell-mediated immunotherapy with family-related haploi dentical lymphocytes following autologous bone marrrow transplantation in o rder to evoke a graft-vs-leukemia effect in the autologous setting. Patients and Methods. Twenty-six patients aged 1.5-48 Sears were enrolled i n this study. Eighteen suffered from acute myeloid leukemia, seven from acu te lymphoblastic leukemia, and one from myelodysplastic syndrome. Eleven pa tients were transplanted in first remission, six in second remission, one i n fourth remission, and eight in relapse. Conditioning consisted of Busulfa n/Cyclophosphamide or Busulfan/Thiotepa/Cyclophosphamide. Nineteen patients (Group A) were treated with gradual increments of haploidentical donor T c ells, starting on day +1, with an additional course of T cells plus intrave nous recombinant human interleukin-2 one month later if no signs of graft-v s-host disease developed in the interim. Seven patients (Group B) were trea ted with high-dose haploidentical T cells on day +1 in conjunction with int ravenous recombinant human interleukin-2. Results. Donor cells were detected in the peripheral blood of both groups 1 2-48 hours post-cell-mediated immunotherapy, peaking at 48 hours. Three pat ients in Group A developed transient Grade I graft-vs-host disease. One pat ient in Group B developed Grade I, and three Grade IV, graft-vs-host diseas e. Group A patients engrafted normally, but the Group B patients with Grade IV graft-vs-host disease showed no signs of engraftment. Conclusion. Our results show that it is feasible to induce graft-vs-host di sease in the autologous stem cell transplantation setting. However, the hig h-dose regimen of haploidentical T cells in conjunction with interleukin-2 results in severe toxicity and nonengraftment. (C) 2000 International Socie ty for Experimental Hematology. Published by Elsevier Science Inc.