As it is well known among oncologists there is no curative treatment
for myeloid leukemia with the exception of bone marrow transplantation.
However only a minority of the population can benefit from this procedure
in that about 70% do not have donors. When donors are available there is
always treatment associated toxicities, the chance of Graft Versus Host
Disease and the propability of relapse. Recent work has shown that
besides the existence of a graft versus host reaction there is also a
graft versus leukemia effect which seems to be mediated by the immune
cells of donor origin.
Additionally there was some belief that graft versus host is
mediated via Th1 type cells and that administration of Th2 cytokines such
as IL-10 may reduce severity of this reaction. A recent publication in
Blood 86:2429 by Sykes et al. demonstrates a potent Th1 cytokine ,IL-12,
as possessing the ability to reduce graft versus host but augment
the graft versus leukemia effect. Work by Slavin's group in Israel also
shows that the Th1 cytokine IL-2 does not exagerbate graft versus host
but augments graft versus leukemia.
My question is, does anyone have any clue as to what the effectors
of this graft versus leukemia effect are? I mean it was published that
CD 4 positive lymphocytes with cytotoxic abilities can be raised against
autologous leukemia cells and the specificity of these clones maintained.
But are these the cells responsible for the in vivo effect? It is known
that in the bone marrow microenvironment suppressive factors exist which
inhibit immune responses from initiating, but is the antileukemic
response in the bone marrow? or is it perhaps mediated through cytokines
released in the periphery? Additionally, it has been shown that leukemic
mononuclear cells are deficient in IL-12 secretion after LPS stimulation,
could there be perhaps a shift from Th0 to Th2 like immune parameters in
the leukemic patient such that there is no response against the leukemia
until after we give the patient IL-2, IL-12, or IFN?
