Autologous Bone Marrow Transplantation - Blog Science Connections

168 Acetaldophosphamide Ex Viuo Chemotherapy
Table 3. Regrowth of CFUs-GM From Acetaldophosphamide-depleted
Bone Marrow
Treatment With
A-ALD
CFUs-GM/Culture (* 103)
(Aig/22* 106/ml/60min) Day 0 Day 6 Day 21 Day 28
A-ALD-treated cultures
0 29.5 30.7 2.1 0.7
6 3.6 33.7 12.0 3.7
10 0.5 17.4 10.3 3.3
12 0 7.1 6.9 4.3
Feeder layer
0 0 ND 0.10 0.12
Abbreviation: CFUs-GM, granulocyte-macrophage colony-forming units.
culture. The initial increase in A-ALD-treated cultures is largely proportional to
the number of surviving CFCI-GMs. The CFCI-GM 7D compartment in cultures of
untreated control marrows is maintained at initial size. After 3 and 4 weeks,
however, the size of the CFG-GM compartments in A-ALD-pretreated CFU-
GM-depleted cultures actually overshoots the size in controls. In control
cultures containing feeder layers, the number of CFG-GM released and
detected was less than 1% of CFUs-GM in flasks containing depleted marrow
treated with 12 ug/m\ of A-ALD.
DISCUSSION
Our results demonstrate that the newly synthesized aldophosphamide
analogue acetaldophosphamide acts on both classes of human marrow-derived
CFUs-GM as 4-HC does but is more toxic by weight and on a molar basis. To
determine whether its ex vivo effect depends less on cell concentration during
drug exposure than does that of 4-HC (3) will require further comparative
studies. Data showing survival of CFU-GMT
5 d
in marrow exposed at a higher cell
density seem to indicate such a possibility. Our work with A-ALD-treated
marrow grown in long-term suspension cultures clearly indicates A-ALD's
selective effect on various cell compartments. Regrowth kinetics of CFU-GM 7 D
in cultures depleted of these cells by A-ALD strongly favors its sparing effect on
CFU-GM precursor cells, the putative stem cells. Our most recent studies of
early regrowth kinetics of CFUs-GM after their depletion by A-ALD further
support the theory of CFU-GM repopulation from their progenitor cell pool;
absence of such regrowth in marrow depleted of CFU-GM to a comparable
degree by x-irradiation and maintained under identical conditions (M. Beran,
unpublished results) lends further support to selective action of A-ALD. When
compared with regrowth of CFUs-GM in long-term cultures of marrows
depleted by 4-HC (2), the CFU-GM recovery after A-ALD appears both more
rapid and more extensive. Whether this sparing effect is the result of an