Autologous Bone Marrow Transplantation - Blog Science Connections

430 Purged Marrow Engraftment in Neuroblastoma
(CF(Js-GM) are considered (data not shown). Of interest is the observation that
marrow harvested from patients receiving previous radiotherapy often contained
fewer CFCIs-GM (12.6 ± 8.3 x 10 4 /kg compared with 17.5 ± 9.3 x 10 4 /kg),
although the total nucleated cell numbers were similar in harvests from both
irradiated and nonirradiated patients (3.63 x 10 8 /kg compared with 3.72 x
10B/kg).
DISCUSSION
This pilot project shows the feasibility of hematologic support through
autologous marrow infusions for children with disseminated neuroblastoma
undergoing marrow-ablative therapy with curative intent. The purging technique
that we have used compares favorably in both safety and efficacy with other in
vitro physical separation and cytotoxic methods. No complement is needed, no
toxin is introduced, and normal hematopoietic cells are unaffected. It is also
adaptable for removing other malignant cells from marrow.
We encountered no difficulties with transporting marrow for in vitro
treatment, and the viability of hematopoietic cells is such that marrow can be
shipped throughout the North American continent. With careful coordination,
this capability permits the development of multicenter clinical trials in which the
purging procedure is carried out at a single institution.
Although we cannot prove that immunomagnetic purging eliminates the
risk of reseeding the patient with malignant cells, extensive testing indicates that
it consistently removes all neuroblastoma cells detectable by currently available
assays. Of concern is the delayed engraftment and nonengraftment that we
observed in four patients. We believe that these problems are owed primarily to
the quality of the marrow harvested rather than the procedure used for purging.
In particular, marrow collected from patients who suffered prior relapse and
who were heavily pretreated, particularly with a combination of chemotherapy
and skeletal and/or abdominal irradiation, may have limited hematopoietic
potential, even when the nucleated cell count appears adequate. For this reason
and because patients who have relapsed are probably more resistant to
chemotherapy, we believe that it is essential to harvest bone marrow for purging
when patients enter initial remission and their marrow is cytologically free of
tumor. More extensive studies are needed to establish if ablative therapy is more
effective when given at an early clinical stage before signs of disease progression.
We cannot draw firm conclusions yet about the efficacy of our protocol for
treating patients with neuroblastoma at high risk of relapse. Others have
achieved similarly promising results in single-arm studies of such therapy. The
Pediatric Oncology Group is about to undertake a prospective multicenter
study to compare autologous or allogeneic marrow transplantation with the
best available conventional therapy in newly diagnosed children with disseminated
neuroblastoma. This is the essential next step in establishing the
value of such therapy in this refractory cancer.