autologous blood and marrow transplantation - Blog Science ...

96 Chapter 2: ALL
Table 1. Summary of outcome for CR2 ALL (excluding children with late relapses)
Therapy EFS TRM
Chemotherapy 10% 15%
AutoBMT 20% 15%
Matched sibling donor BMT 50% 25%
Unrelated donor BMT 40% 50%
leukemia has remained an important question. Studies in which the leukemia
contamination was quantitated by an in vitro progenitor assay done before purging
as an indicator of pretransplant leukemia burden, and then done after purging,
indicate that it is the burden of leukemia remaining at the time of BMT that
determines relapse and not the burden of leukemia infused. 9
The availability of
sensitive molecular detection methods may allow a better assessment of leukemia
burden pre- and postpurging of bone marrow, and also may allow better selection
of patients as candidates for autoBMT. 10
Recently, the use of peripheral blood stem
cells has been identified as an interesting source for grafting which may have a
lower burden of leukemia, but if in vivo leukemia burden is not eradicated, it may
not lead to significant improvements in outcome. Overall, improvement in outcome
with autoBMT for ALL will require improvements in "in vivo" purging.
In contrast to autoBMT, UD BMT has a relatively low relapse rate but high
transplant-related mortality, both of which are related to GVHD. The existence of
a GVL reaction for ALL is now unequivocal, based on lower relapse rates after UD
vs. MSD BMT, 6
correlation of lower relapse rates with occurrence of GVHD, 11
and
an antileukemia effect of donor leukocyte infusions for relapses of ALL post-
1 2
BMT. A GVL effect for first-remission ALL in matched sibling donor BMT was
1 3
found to be correlated with acute GVHD but not chronic GVHD.
In contrast to
both acute and chronic myeloid leukemias (AML and CML), there does not appear
to be a GVL effect independent of GVHD. This may make for a very difficult
situation in terms of improving outcomes of UD BMT for ALL, since GVHD is the
largest contributor to treatment failure, and attempts to abrogate GVHD may very
well lead to higher relapse rates. A hypothetical breakdown of the components of
both auto- and UD BMT as they contribute to outcome in patients with high-risk
ALL is listed in Table 2.
AUTOLOGOUS GVL REACTIONS
An approach to improving autoBMT might then be to mimic a GVL effect
without generating fatal GVHD. One approach is through modulation of the host
immune system with agents that can induce autoimmune reactions. This has been
1 4
demonstrated in autoBMT for AML with use of post-BMT cyclosporine A.