Autologous Bone Marrow Transplantation - Blog Science Connections

Merocyanine 540 Marrow Decontamination 155
10CH
AZ:100 ug/ml
MC:15 ug/ml
o
c
o
o
o
sol
i
i
AZ
MC540
90
AZ
MC540
MC 540
+
AZ
Figure 2. Effect of mafosfamide (AZ), merocyanine 540 (MC; MC 540), or both on murine
spleen colony-forming units on day 11. Values are means from three to six experiments
plus or minus the standard error. Colony-forming units were derived from spleen colony
assays in 22-31 surviving recipient mice. Results are expressed as a percentage of values
from the control
suspension.
In our model, when the clonogenic cell frequency was 5% of the total cell
number, both mafosfamide and MC-540 proved able to effectively eliminate all
acute leukemia CCRF-SB lymphoblasts present in the cell mixtures. In the
mixtures containing K562 cells, both agents yielded a result of 1 residual blast
per 10 4
cells of cleansed mixture (i.e., 99.97% decontamination).
To define the decontaminating limits of these two agents, we tested both
agents alone and in combination with cell mixtures in which the clonogenic cell
frequency had been increased to 15%. In the case of CCRF-SB cells,
mafosfamide was able to yield a satisfactory result, but with the K562 cells the
results were dismal.
Combined treatment with mafosfamide followed by the photosensitizer
MC-540 proved no longer toxic on pluripotentday 11 CFC1-S (Fig 2). With K562
cells, the combined treatment was equally ineffective, but with the CCRF-SB line
results improved when MC-540 was added to mafosfamide, residual blasts
dropping from 0.6/well to 0.25/well. It should, however, be noted that the CE
proved very low (Table 1; Fig 1), which may reflect a high number of residual
leukemic cells. In this case, the increased proliferation rate of the residual
leukemic cells, as measured by tritium-labeled thymidine uptake, can give rise
to false-negative results and hence an unexpectedly high proportion of negative
wells. In our microtray assay system, though cultures are refed periodically,