Autologous Bone Marrow Transplantation - Blog Science Connections

Mafosfamide Purging in Leukemia 83
Determination of the Optimal Mafosfamide Dose
Because of the inability, at least with routine laboratory techniques, to
evaluate the risk of injuring pluripotent stem cells when destroying all CFCI-GM,
we defined the optimal mafosfamide dose for in vitro treatment of the whole BM
as the dose that spares 5% of residual CFCI-GM. As shown in Figure 1, the LD 9 5
definition zone for most patients spreads over 14-30 jug/2 x 10 7
buffy coat
cells. In our experience, this allowed an accurate and reliable determination of
the appropriate dose on a PIT. In a series of 32 marrow-cleansing procedures
(for 24 patients in the clinical trial and 8 additional ones), residual CFCI-GM were
evaluated after incubation of the whole BM with the predetermined dose, and
the results were compared with those given by the PIT. In 25 cases, in which all
the technical parameters were adequate, the actual CFCI-GM recovery measured
after treatment of collected marrow was correlated with the expected recovery
predicted by the PIT curve (r = .473, P < .03), and accuracy of the recovery was ±
4%. In the other seven cases, discrepancies were observed that could be
retrospectively attributed either to an excessive hematocrit at time of bone
marrow incubation, an inappropriately low temperature of the incubator, or the
presence of cell aggregates. Figure 1 shows that if we decided to incubate all
marrows with a standard dose of mafosfamide, rather than adapt the dose to
each patient, the best choice of dose would be 70 ug/2 * 10 7
cells, which would
fit our objective of leaving 5% residual CFCI-GM in 35% of the patients. With this
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D W 20 30 40 SO »0 '0 M> «O 100 HO 120 130 MO »50
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Figure 1. Individual susceptibility of granulocyte-macrophage colony-forming units to
mafosfamide (Asta Z 7557). (Reproduced from Blood, vol. 67, 1986, with permission of
Grune & Stratton.)