Autologous Bone Marrow Transplantation - Blog Science Connections

24 First-Remission Autograft forAML
syngeneic transplants for AML in first remission (4). More recent experience
with the use of T-lymphocyte depletion, which provides protection from GVHD,
may show higher rates of relapse in AML similar to those already observed in
chronic granulocytic leukemia after the use of this technique (5).
For many researchers and clinicians, the major conceptual objection to
autografting in acute leukemia is the assumption that, because relapse of
disease seems inevitable, the autograft is certain to contain occult leukemia
cells that will inevitably result in disease recurrence. This traditional view may
not be inconsistent with the possibility of achieving a measure of success. In
addition, a proportion of the leukemic blast cells are lost during storage. Few
clonogenic cells may remain to be reinfused if it is considered that no more than
1 -2% of marrow cells are harvested from the patient in remission who may have,
at most, a similar percentage of blast cells present, of which fewer than 10% are
clonogenic, and they may even seed to the irradiated marrow microenvironment
less efficiently than normal hematopoietic precursors. Although it cannot be
denied that residual leukemic cells contaminating the marrow may result in
relapse, perhaps the major problem remains eradication of the disease from the
patient. There should be little doubt that this is the major obstacle to success, as
indicated by the fact that currently used regimens failed to eradicate the disease
in half the syngeneic grafts.
In the majority of clinical studies done in recent years, no attempt was
made to remove occult disease from the autograft. Whether there are effective
ways of doing this remains debatable. These studies indicated that about 50% of
patients remain disease free (6,7). Although these patients require longer
follow-up, the negligible difference from syngeneic results suggests that
residual disease in the graft may currently be a minor issue.
A valid criticism of the autograft data so far is that several of the procedures
were done for patients who had already been in remission for several weeks and
therefore had an improved prognosis anyway.
There is little doubt that, to ensure the best results, first remission is the
optimum time for autograft. But timing is still one of the important remaining
issues: When in first remission should the autograft be incorporated into the
overall treatment protocol?
THE GLASGOW AUTOGRAFT EXPERIENCE—AN UPDATE
Since 1981 in Glasgow, patients with AML in first remission have been
offered ablative chemoradiotherapy as remission consolidation. If they were
younger than 40 years and had a donor with identical homologous leukocytic
antibodies, allogeneic marrow transplant was the treatment of choice. Those
who did not have a donor and were up to 55 years old were offered autograft.
Twenty-three patients have received ABMT. Before the procedure, all
patients received induction and consolidation chemotherapy involving daunorubicin,
cytosine arabinoside, and 6-thioguanine, but the number of courses
and the durations of remission before the autograft differed.