Adoptive immunotherapy using donor leukocytes following bone marrow transplantation for chronic myeloid leukemia: is T cell dose important in determining biological response?
We investigated the use of donor leukocytes for the treatment of Epstein-Barr virus (EBV) lymphoproliferative disease following T cell-depleted bone marrow transplantation (BMT) for chronic myeloid leukemia (CML). We wanted to determine whether donor leukocyte treatment would result in altered biological responses with respect to anti-EBV lymphoma activity, donor-host chimerism and graft-versus-leukemia (GVL) responses. Three patients with CML in cytogenetic remission received < 10(6)/kg donor leukocytes for treatment of EBV lymphoproliferative disease. Lineage specific chimerism and residual leukemia detection were assessed using sensitive PCR methodologies. Following donor leukocyte treatment 1 patient had no recurrence and the other 2 had responsive EBV lymphoma. The 2 patients who were mixed T cell chimeras before treatment, remained so after treatment. Two were BCR-ABL positive by PCR before and after treatment and both developed hematologic relapse. None of the 3 patients developed acute graft-versus-host disease (GVHD) with 1 patient developing limited chronic GVHD. These data suggest that small numbers of donor T cells can eradicate EBV lymphoproliferative disease but may not alter donor-host chimerism or mediate GVL responses.
Mackinnon
S
S
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Papadopoulos
E B
EB
Carabasi
M H
MH
Reich
L
L
Collins
N H
NH
O'Reilly
R J
RJ
D000328:Adult; D016026:Bone Marrow Transplantation; D005260:Female; D004854:Herpesvirus 4, Human; D006801:Humans; D007155:Immunologic Factors; D016219:Immunotherapy, Adoptive; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000628:therapy*; D008232:Lymphoproliferative Disorders / Q000628:therapy* / Q000821:virology; D008297:Male; D012008:Recurrence; D012074:Remission Induction; D013601:T-Lymphocytes
D007155:Immunologic Factors