Relapse of host leukemic lymphoblasts following engraftment by an HLA-mismatched marrow transplant: mechanisms of escape from the "graft versus leukemia" effect.
Leukemic relapses and graft versus host disease (GvHD) remain major complications following allogeneic bone marrow transplantation for leukemia. We present clinical and laboratory details for an eight-year-old boy who received a T-cell-depleted HLA-mismatched marrow transplant as therapy for acute lymphoblastic leukemia (ALL) in second remission. Engraftment with donor marrow was prompt and without any acute GvHD. Nevertheless, the patient's original ALL recurred and proved fatal. The patient remained a chimera with persistent donor lymphocytes present at the time of posttransplant relapse and subsequent to treatment with unsuccessful reinduction chemotherapy. In vitro immune studies showed that these leukemic cells could be recognized and destroyed by the donor's lymphocytes. The relapse itself suggests, however, that the donor's lymphocytes did not effectively destroy the patient's histoincompatible ALL cells in vivo following establishment of the chimeric state. Potential mechanisms are presented to account for this presumed "escape" from the postulated "graft versus leukemia" effect.
Sondel
P M
PM
Hank
J A
JA
Molenda
J
J
Blank
J
J
Borcherding
W
W
Longo
W
W
Trigg
M E
ME
Hong
R
R
Bozdech
M J
MJ
D000208:Acute Disease; D001853:Bone Marrow / Q000276:immunology; D016026:Bone Marrow Transplantation; D002455:Cell Division; D002648:Child; D002678:Chimera; D003131:Combined Modality Therapy; D003601:Cytotoxicity Tests, Immunologic; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006680:HLA Antigens / Q000276:immunology*; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D007231:Infant, Newborn; D007945:Leukemia, Lymphoid / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D010641:Phenotype
D006680:HLA Antigens