Influence of cytokines and autologous lymphokine-activated killer cells on leukemic bone marrow cells and colonies in AML.
We have already shown that cytokine cocktails (IL-1beta, IL-3, IL-6, SCF, GM-CSF) and/or lymphokine-activated killer (LAK) cells can reduce the amounts of clonal, CD34-positive mononuclear bone marrow cells (BM-MNC) in acute myeloid leukemia (AML). In addition, the influence of those cocktails and/or LAK cells on the clonogenic potential of AML BM-MNC was investigated. BM colonies cultured in agar during different stages of the disease were immunophenotyped in situ: 17 patients at diagnosis, 14 patients in complete remission, 8 patients at relapse, 8 healthy donors. A significant reduction in leukemic cells and colonies positive for CD34 after in vitro culture of BM-MNC with cytokine cocktails was achieved with all samples obtained at diagnosis (n = 8, p < 0.01), in 6 of 8 cases in complete remission but only in 2 of 6 cases at relapse. Cytokine cocktails stimulated granulopoiesis as well as B and T lymphopoiesis. Colonies with leukemic phenotype could never be detected in healthy BM. A significant reduction in leukemic colonies was achieved by coculture of BM-MNC (uncultured or cytokine precultured) with autologous LAK cells in all 4 cases at diagnosis and in 1 case at relapse. An additive effect of in vitro cytokine preincubation of BM samples on the leukemia-reducing effect of LAK cells could be demonstrated in all samples studied (p < 0.001; diagnosis: n = 10, relapse: n = 3, complete remission: n = 7). Patients had a better prognosis if CD34-positive colonies in AML could be reduced by cytokine incubation (p = 0.03) or coculture with autologous LAK cells in vitro (p = 0.04). Our data show that cytokines as well as LAK cells alone and in combination can reduce, however not eliminate clonogenic AML cells. Such mechanisms might be responsible for maintaining stable remissions in AML.
Braun
S W
SW
Charité, Campus Virchow-Klinikum, Experimental Surgery, Humboldt University of Berlin, Germany.
Gerhartz
H H
HH
Schmetzer
H M
HM
D000208:Acute Disease; D018952:Antigens, CD34; D001854:Bone Marrow Cells / Q000276:immunology* / Q000473:pathology*; D002454:Cell Differentiation; D002455:Cell Division; D016207:Cytokines / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007167:Immunotherapy; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology* / Q000473:pathology; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured
D018952:Antigens, CD34; D016207:Cytokines