Autologous Bone Marrow Transplantation - Blog Science Connections

Burkitt's Lymphoma Purging Assay 357
Table 5. Summary of the Clonogenic Efficiency of BL Cell Lines in Serial Dilution
Assay or Liquid Culture Assay
Cloning
Cell Lines
Widespread
BJAB (EBV-)
JD-38 (EBV-)
Manalwa (EBV+)
Manalwa (EBV+)
Efficiency 8
15%
26%
34%
50%
Author
de Fabritüs ef al. (10)
de Fabritüs era/. (10)
de Fabritüs era/. (10)
Bast ef al. (9)
Status Undetermined
BLcell line (?)
90%"
Uckun ef al. (12)
Newly Established
BL93
BL 2
BL99
BL 1 7
> 90% c
> 90%
> 90%
> 90%
Philip ef al.
(this chapter)
Abbreviations: BL, Burkitt's lymphoma; EBV, Epstein-Barr virus.
"Estimated on the basis of published results.
b
Optimal growth in control samples at 1% BL cell concentration.
°Good outgrowth at a wide range of conditions (i.e., one residual cell among 4 x
10 6 normal bone marrow cells).
exploited for quantifying the efficacy of purging against Burkitt's cells of various
origins and different characteristics. Apparently the phenotypic features of
these lines presumably reflect the heterogeneity of the disease in the individual
patients (4,5). However, the liquid culture assay has the following limitations:
this test indicates the range of residual malignant cells in the samples rather
than their precise numbers, and though very sensitive in determining whether
the cleaning of the bone marrow is complete (> 3 log kill), it is less sensitive in
assessing the elimination under 2 logs.
More recently, we used the liquid culture to assay the efficiency of these
purging procedures on fresh tumor samples, either invaded bone marrow or
autologous nonirradiated bone marrow contaminated with fresh BL cells from
the initial site of the disease. Preliminary results show that the level of sensitivity
is close to that observed with the cell lines, and for four patients we were able to
demonstrate the growth of malignant cells prior to the clinical purging
procedure and its inhibition after the procedure. As shown for patient 7 (Table
4), this assay allows the selection of the relevant monoclonal antibodies in the
complement lysis procedure or, as in patient 6, the comparison of the efficiency
of immunomagnetic depletion and that of complement lysis.
Most purging procedures described have now been refined in terms of
toxicity and efficiency and are capable of eliminating 3 logs of malignant cells.
The next step is to transfer such procedures into clinics and to study the ability
of such procedures to cleanse bone marrow with minimal involvement. As we