autologous blood and marrow transplantation - Blog Science ...

420 Chapter 7: Solid Tumors
TANDEM TRANSPLANTS WITH CD34-POSITIVE AND -NEGATIVE CELLS
Dose intensification and sequential use of agents to overcome drug resistance
may benefit some patients, and interest in the concept of tandem transplants has
been growing. To improve the therapeutic efficacy under these conditions by
depleting contaminating tumor cells in the grafts, positively selected CD34 +
cells
have been used. To maximize the intensity of therapy at an acceptable cost in
toxicity, we developed a new tandem transplant strategy, in which cells recovered
in the CD34~ fraction, which still contains a large amount of clonogenic progenitor
cells identified as CFU-GM, are used in the initial transplant. 7
This was followed
by two to three courses of regular-dose chemotherapy without rescue for further in
vivo purging before the final transplant with purified CD34 +
cells, which enables
the ultimate eradication of reinfused cancer cells. Identical carboplatinum-based
regimens consisting of cyclophosphamide (1.2 g/m 2
X 2 days) and melphalan (90
mg/m 2
X 2 days) were used for both courses of high-dose therapy. Currently, 13
patients have been treated. The number of CFU-GM infused and the subsequent
engraftment speed after each transplant procedure were identical.
Based on the results, we conclude that this approach makes multiple-course
combination high-dose therapy more feasible by ameliorating cytopenia with an
improved cost/benefit ratio. Although tumor cells contaminating the CD34~
fraction might be of clinical concern, the presence of these cells in the graft is not
necessarily capable of producing a relapse of the disease on reinfusion. This risk
associated with our procedure must be weighed against the likelihood of a
significant benefit. We believe that the number of cancer cells in the first graft is
far smaller than the tumor burden remaining in the entire body at the first transplant
and that infused cancer cells can be purged by the subsequent transplant.
Nevertheless, recognizing that cancer cells might be enriched in the CD34~
fraction, the use of an additional purification of this fraction for negative depletion
of cancer cells will be evaluated.
FACILITATED ENGRAFTMENT BY INTRAMEDULLARY ADMINISTERED
ENRICHED CD34+ CELLS?
Stem cell products are commonly infused into the venous system following
myeloablative chemoradiotherapy. Hence, it is likely that only a few cells enter the
marrow space, since many cells are "trapped" in the microcirculation, including the
reticuloendothelial system, pulmonary vessels, and other capillary beds during the
first pass through the systemic circulation. When the harvested graft is
manipulated, there is a significant loss of cells and graft failure becomes a major
concern. Therefore, we hypothesized that direct puncture of the marrow cavity to
implant the graft might provide a more stable engraftment. In clinical transplan-