Autologous Bone Marrow Transplantation - Blog Science Connections

Purged ABMT in CR of Acute Leukemia 21
one; and primary biliary cirrhosis, one. Except for the patient with graft-versushost
disease features, who died of gastrointestinal bleeding, all other
autoimmune manifestations were resolved either spontaneously or with steroid
therapy.
Three patients developed chromosomal abnormalities that, in two of them,
involved chromosome 1. Two of these patients are disease free at 11 and 41
months after transplantation: one still has chromosomal abnormalities in a
small faction of marrow cells; in the other, these disappeared 10 months after
the surgery. The third patient, who had ALL, relapsed and died 19 months after
transplantation without resolution of the chromosomal abnormalities. We
postulated that marrow incubation with mafosfamide is responsible for the
genesis of these aberrations.
CONCLUSIONS
We drew the following conclusions from the present status of our clinical
trial:
1. In adult patients with acute leukemia in first remission and who do not
have identical siblings, ABMT may offer a chance similar to that of allogeneic
bone marrow transplantation.
2. Results at the moment look more favorable for AML than for ALL
patients, with disease-free periods of 58% at 4 years for the former and 40% at 3
years for the latter. Strikingly enough, the very low incidence of leukemic
relapses in standard-risk patients with AML in first remission ( 35% ) as well as a later occurrence of relapse in patients with
ALL.
3. The design of our study precludes any estimation of the value of our
marrow-purging procedure—mafosfamide at dosage determined according to
the sensitivity of stem cells in each patient. Obviously, an evaluation would have
required a randomized trial to compare ABMT with purged and nonpurged
marrow. Such trials are in progress in several institutions (9). Although results
of the European Bone Marrow Transplantation Group (EBMTG) registry do not
at the moment indicate any advantage of marrow purging over nonpurging
(10), the low rate of leukemic relapses in our AML patients contrasts with the
42% incidence rate in the EBMTG study, suggesting that our study, which
involves a small number of patients, should be pursued.
4. In AML, prolonged delays in platelet recovery increase the rate of deaths
from toxic effects, which makes urgent a rapid evaluation of the antitumor effect
of our marrow-purging procedure in order to consider reducing the dose of
mafosfamide used (CFCl-GM LD 9 0
or lower).
5. Finally, late relapses in ALL may justify some increase in the therapeutic
maneuvers. Consideration may be given to an increase in the pretransplantation
consolidation regimen, perhaps with additional cytosine arabinoside; the
introduction of maintenance chemotherapy after ABMT; and double autografting.