Autologous Bone Marrow Transplantation - Blog Science Connections

Summary 741
T cell-depleted bone marrow grafts. The analysis of the European Bone
Marrow Transplantation Group (EBMTG) did not indicate a difference between
purging and no purging (8), but this study is a retrospective one and not
a controlled clinical trial.
The general impression is that ABMT in first-remission patients with
acute nonlymphocytic leukemia (ANLL) may result in similar survival rates as
are being obtained with allogeneic BMT, but the follow-up periods are not yet
long enough to provide insight into late relapse rate.
Several speakers suggested that TBI is not necessary in the conditioning
for ABMT, which might be an advantage in the long run. As alternative
cytotoxic treatment, they employed high-dose combination chemotherapy,
such as BCNCI (carmustine), m-AMSA, cyclophosphamide, VP-16-213 (etoposide),
or carmustine, Adriamycin (doxorubicin), ara-C (cytarabine), cyclophosphamide,
and thioguanine.
Goldstone showed that the latter regimen could be repeated followed by
a second ABMT (so-called double autografting) in some patients. The basic
idea underlying double grafting is to accumulate the cytoreductive (antileukemic)
effect and to affect an "in vivo purging" of the bone marrow. Many
patients, however, cannot tolerate double grafting so that a selected subgroup
of only 40% proceeded to the second graft.
Both Lowenberg and Gorin observed a slower recovery of platelets and
granulocytes in their autografted patients than is seen after allografting.
Although this difference was particularly apparent in patients with ANLL, it
was not in patients with acute lymphocytic leukemia (ALL). Both ALL and
ANLL patients have received similarly severe chemotherapy before their
marrow was harvested, so it is unlikely that this factor accounts for this
phenomenon. The delayed hematopoietic regeneration after ABMT might be
disease related, although the underlying mechanism remains obscure at
present. One explanation that came to my mind was based on a difference
Prins and 1 observed in spatial distribution of cells in rat models of acute
myelogenous leukemia (AML) and ALL (9). With the progression of AML in
the bone marrow we found that AML blasts tend to occupy the sites that are
preferred by stem cells (i.e., the endosteal surfaces), while ALL blasts are
distributed randomly over the bone marrow. This has led to a more rapid
replacement of stem cells by AML blasts with a resulting steeper decrease in
stem cell numbers than in ALL.
There is general agreement that questions on the value of ABMT can only
be solved by appropriate prospective randomized trials, such as were started
in 1984 by a Dutch ABMT study group and reported by Lowenberg. So far, 29
patients have been entered in the autologous marrow arm of this study, and
eight of these patients have relapsed. The study is continuing.
Results of ABMT in leukemia patients during second or subsequent
remissions were reported by several speakers. In general, survival is less than
that observed in patients treated in first remission and that difference is