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T Hercend, T Takvorian, A Nowill, R Tantravahi, P Moingeon, KC Anderson, C Murray, C Bohuon, A Ythier and J Ritz
To identify cells with potential antileukemia activity following bone
marrow transplantation, we have monitored immunologic reconstitution in a
patient with acute lymphocytic leukemia in second remission who received
intensive chemotherapy and total body irradiation followed by infusion of
allogeneic histocompatible marrow. Prior to transplantation, donor bone
marrow cells were depleted of T lymphocytes by in vitro treatment with
anti-T12 monoclonal antibody and rabbit complement. In the first 3 weeks
following bone marrow transplantation, the predominant regenerating
mononuclear cell population in peripheral blood exhibited a phenotype
characteristic of natural killer (NK) cells. After 4 weeks, T lymphocytes
became predominant, but NK cells persisted. Cultured peripheral blood
lymphocytes obtained 12 weeks posttransplant were able to display
significant cytotoxicity against leukemic blasts that had been
cryopreserved at the time of relapse 5 months prior to bone marrow
transplantation. To further characterize those cells with antileukemia
activity, we used in vitro cloning techniques to identify four monoclonal
populations, termed TC12, -48, - 50, and -59, with strong antitumor
activity. Cytogenetic analysis demonstrated that each clone was of donor
origin. Phenotypic characterization showed that the four clones expressed
NKH1A but did not express T3, T4, or T8 antigens. Three of the four clones
expressed T11/E rosette antigen. Each clone exhibited strong cytotoxicity
against genetically unrelated hematopoietic tumor cell lines such as K562,
Molt- 4, JM, and U937. In addition, we found that these patient clones were
similar to cloned NK cells previously derived from normal individuals.
Taken together, these results suggest that at least some clones with
antileukemia activity following bone marrow transplantation are cells with
NK-like function and phenotype. Functional analysis of these cytolytic
cells in larger numbers of patients will be necessary to determine the
clinical significance of this finding.
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