Autologous Bone Marrow Transplantation - Blog Science Connections

700 Conditioning Regimens in AML
cytosine arabinoslde
cyclophosphamide
Vm 26
TBI
cyclophosphamide
(f)TB
7
^
busulphan
cyclophosphamide
piperazinedione
• melphalan
BCNU
AMSA
VP 16
cytosine arabinoside
6-thioguanine
cytosine arabinoside
CCNU
cyclophosphamide
BCNU
adriamycin
cyclophosphamide
cytosine arabinoside
6-thioguanine
Figure 1. Ablative conditioning regimens preceding bone marrow transplantation in
patients with acute leukemia.
of ablative chemo- and radiotherapy, and not the presence of reinfused
leukemic cells in the autologous marrow graft. Arguments for this statement
are: 1) Similar relapse rates occur after autologous and isologous BMT.
2) Leukemia relapses occur at about the same time after autologous, isologous,
and allogeneic BMT, median of 9 months. 3) The ED 5 0
for human AML is
KP-IO 4
clonogenic cells (extrapolated from preclinical data in the brown
Norway rat AML (Leuk Res 1985;9:1389-1395). 4) So far in vitro "purging" has
had no beneficial effect.
The differences in efficacy of different conditioning regimens in eradicating
residual leukemia in the host lack a quantitative basis in terms of log
leukemic cell kill. In parallel to the clinical studies, therefore, the antileukemic
effect of the components of two conditioning regimens were evaluated in AML
in the brown Norway rat as a relevant model for AML: CY with TBI, and ÇY with
Bu. All experiments were initiated on day 13 after inoculation with 10 7
brown
Norway rat myelocytic leukemia (BNML) cells. At that particular stage the total
leukemic cell load amounts to 5 x 10 9 -10 10
cells.
MATERIALS AND METHODS
Rats
The experiments were performed with the inbred brown Norway rat strain
produced in the Rijswijk colony. Male rats between 13 and 16 weeks of age and
a mean body weight of 200 g were used.
The Rat Leukemia Model
The origin, classification, transplantation procedure, and growth characteristics
of the BNML model have been described in detail elsewhere (2,3).