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Autologous Bone Marrow Transplantation - Blog Science Connections

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Purging Methods in Burkitt's Lymphoma 363<br />

very sensitive to the complement lysis; in contrast, the IMD procedure provided<br />

an optimal BL cell elimination on the BLg 3<br />

cell line partially resistant to<br />

complement. The analysis of individual experiments, in which one or the other<br />

procedure failed, supplied complementary data, as shown in the three<br />

examples of Table 3. Indeed, we demonstrated a complementarity between the<br />

two immunologic procedures. It has been previously reported that chemical<br />

(mafosfamide) and immunologic purging methods have additive effects<br />

(6-10). Such a complementary effect could appear more surprising in the case<br />

of two immunologic methods. It is in fact quite logical if one remembers that the<br />

resistance of malignant cells to complement lysis (as shown for BL 9 3<br />

) is<br />

relatively independent of the monoclonal antibody used and that quality criteria<br />

required from monoclonal antibodies and the recognized antigen in the IMD are<br />

different from those required in the complement lysis procedure (see V.<br />

Combaret et al. in this volume).<br />

CONCLUSION<br />

Our work shows that one or the other procedure enables us to purge a<br />

bone marrow having minimal involvement (i.e., 1% or less), but a few<br />

unpredictable partial failures were observed with both methods. Considering<br />

such results, we are tempted to propose combining the purging methods, to<br />

allow the cleansing of bone marrow contaminated by more than 1% malignant<br />

cells and to avoid the few failures we observed. We will, however, strongly reject<br />

such an idea. Indeed, in the first hypothesis, if the marrow contains more than<br />

156 malignant cells, it could probably be purged by a combination of these<br />

procedures, but the peripheral disease would not be eradicated by high-dose<br />

chemotherapy. In the second hypothesis, in order to avoid a few failures in some<br />

patients it is unacceptable to increase for all of them the toxicity and the cost of<br />

the purging by combining two procedures. We will, therefore, suggest a purging<br />

"a la carte" for which optimal monoclonal antibodies and consequently optimal<br />

methods will be selected for each patient in a preclinical assay (4; see also 1.<br />

Philip et al. in this volume). Such an approach is certainly a very difficult one for<br />

laboratory investigators but could allow the evaluation of the purging method<br />

Table 3. Complementary Effects of Two Immunologic Procedures<br />

Mean Cell Kill<br />

(log)<br />

Cell<br />

Line<br />

Complement<br />

Magnetic<br />

Depletion<br />

BL99 >5 2<br />

BL93 2 >5<br />

BL 2 >5 3<br />

Note: These three individual experiments (one on each line) are part of Table 2<br />

results and are given as examples. When one of the two techniques fails, the other one<br />

is highly<br />

efficient.

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