Graft versus Leukemia

T Ichim TEICHIM at AHS.watstar.uwaterloo.ca
Tue Mar 26 00:00:27 EST 1996

     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?

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