Induction of a syngeneic graft-versus-leukemia effect following bone marrow transplantation for chronic myeloid leukemia.
Although clinical data support the concept of a graft-versus-leukemia (GVL) effect following allogeneic bone marrow transplantation (BMT), there are few data to support a similar GVL activity following syngeneic BMT in man. To identify cells with a potential antileukemic activity post-BMT, we monitored the immunological reconstitution in a patient with chronic phase chronic myeloid leukemia (CML) who received a syngeneic BMT from his identical twin brother. Peripheral blood mononuclear cells (PBMC) from the donor prior to the transplant and from the recipient posttransplant were cultured with recombinant interleukin-2 to generate lymphokine activated killer (LAK) cells. LAK cells from both sources lysed the cell line target cells K562 and LCL and also recipient and allogeneic CML target cells in a 51Cr release cytotoxicity assay. Donor-derived LAK cells did not kill normal donor marrow. LAK cells had similar effects on granulocyte-macrophage progenitor cells (CFU-GM): LAK cells from both donor pre-BMT and recipient post-BMT inhibited the proliferation of CFU-GM from the patient's CML cells, but again donor LAK cells did not inhibit the colony growth of normal donor marrow. These results suggest that a syngeneic GVL effect is inducible following BMT in man and that this activity may be truly antileukemic and spare normal marrow progenitors.
Mackinnon
S
S
MRC/LRF Leukaemia Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, U.K.
Hows
J M
JM
Goldman
J M
JM
D000328:Adult; D000951:Antigens, Neoplasm / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology*; D003114:Colony-Forming Units Assay; D006087:Graft vs Host Reaction / Q000276:immunology*; D006098:Granulocytes / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000276:immunology / Q000601:surgery*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000502:physiology; D008297:Male; D010641:Phenotype; D014185:Transplantation, Isogeneic / Q000276:immunology*
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D007376:Interleukin-2