Adoptive immunotherapy with haploidentical allogeneic peripheral blood lymphocytes following autologous bone marrow transplantation.
Patients who undergo autologous bone marrow transplantation for acute leukemia are at high risk for relapse. We have evaluated the feasibility of administering cell-mediated immunotherapy with family-related haploidentical lymphocytes following autologous bone marrow transplantation in order to evoke a graft-vs-leukemia effect in the autologous setting.Twenty-six patients aged 1.5-48 years were enrolled in this study. Eighteen suffered from acute myeloid leukemia, seven from acute lymphoblastic leukemia, and one from myelodysplastic syndrome. Eleven patients were transplanted in first remission, six in second remission, one in fourth remission, and eight in relapse. Conditioning consisted of Busulfan/Cyclophosphamide or Busulfan/Thiotepa/Cyclophosphamide. Nineteen patients (Group A) were treated with gradual increments of haploidentical donor T cells, starting on day +1, with an additional course of T cells plus intravenous recombinant human interleukin-2 one month later if no signs of graft-vs-host disease developed in the interim. Seven patients (Group B) were treated with high-dose haploidentical T cells on day +1 in conjunction with intravenous recombinant human interleukin-2. Donor cells were detected in the peripheral blood of both groups 12-48 hours post-cell-mediated immunotherapy, peaking at 48 hours. Three patients in Group A developed transient Grade I graft-vs-host disease. One patient in Group B developed Grade I, and three Grade IV, graft-vs-host disease. Group A patients engrafted normally, but the Group B patients with Grade IV graft-vs-host disease showed no signs of engraftment. Our results show that it is feasible to induce graft-vs-host disease in the autologous stem cell transplantation setting. However, the high-dose regimen of haploidentical T cells in conjunction with interleukin-2 results in severe toxicity and nonengraftment.
Nagler
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A
Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel. nagler@hadassah.org.il
Ackerstein
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A
Or
R
R
Naparstek
E
E
Slavin
S
S
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D007938:Leukemia / Q000276:immunology* / Q000628:therapy*; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000276:immunology* / Q000628:therapy*; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous