Clonogenicity of circulating neuroblastoma cells: implications regarding peripheral blood stem cell transplantation

Abstract

Peripheral blood stem cells (PBSCs) are being used as an alternative to autologous marrow rescue for hematopoietic reconstitution after high- dose chemotherapy in patients with neuroblastoma and other solid malignancies. Use of PBSCs is preferred by some because of the belief that there is less risk of tumor contamination. Because tumor stem cell contamination is thought to be one contributing cause of relapse after myeloablative therapy and autologous reconstitution, we examined the potential risk of reinfusing circulating neuroblastoma cells by in vitro evaluation of their clonogenicity. Immunocytologic and tumor cell clonogenic analyses were performed on 74 blood samples obtained from 56 children with advanced-stage neuroblastoma. Concurrently drawn bone marrow specimens were evaluated in 30 instances. Circulating neoplastic cells were detected in 19 of 74 (26%) for all specimens and by immunologic techniques (26%). Using a clonogenic assay, 13 grew identifiable tumor colonies. Comparing results with the two techniques showed tumor colony growth in 10 of the 19 positive specimens by immunocytology. However, 3 of 53 samples (6%) that were negative by immunocytology were positive by the clonogenic assay. Of the 11 positive blood samples, 9 concurrent marrows contained neuroblastoma cells; of the 19 negative blood specimens, 3 concurrent marrows had metastatic disease. We conclude that circulating neuroblastoma cells are present in peripheral blood and have clonogenic properties in vitro. This supports the view that tumor cell contamination may well be one cause of relapse after autologous reconstitution. Consequently, PBSC collections should also undergo meticulous monitoring for tumor contamination before autologous reinfusion.

Mobilization of Myeloma Cells Involves SDF‐1/CXCR4 Signaling and Downregulation of VLA‐4

“…Comobilization of tumor cells following chemotherapy or growth factor has also been documented for hematological malignancies [15][16][17][18][19][20][21] and for solid tumors [22][23][24]. leukemia [34][35][36], non-Hodgkin's lymphoma [37][38], chronic myelogenous leukemia [39], and acute leukemias [40,41].…”

Minimal residual disease at the time of peripheral blood stem cell harvest in patients with advanced neuroblastoma

“…Although high-dose chemotherapy and subsequent haemopoietic rescue are widely used in the treatment of patients with advanced neuroblastoma, the value of removing tumour cells from bone marrow or peripheral stem cells prior to reinfusion remains controversial. The clinical significance of reinfusing neuroblastoma cells during transplantation procedures has been questionable, although recent studies demonstrating the clonogenic properties of tumour cells isolated from peripheral blood [4] and the identification of reinfused tumour cells at the site of metastases [5,6] suggest that they may play a role in the development of secondary disease and relapse.…”

Multiple myeloma: reduced plasma cell contamination in peripheral blood progenitor cell collections performed after repeated high‐dose chemotherapy courses

“…Reinfused tumour cells may contribute to disease recurrence following autograft, as suggested by recent studies in patients with haematological and extrahaematological malignancies (Brenner et al, 1993;Zwicky et al, 1996;Moss et al, 1994). A correlation between autograft with heavily contaminated material and relapse has been also suggested for MM (Gazitt et al, 1996;Henry et al, 1996;Vescio et al, 1996;Schiller et al, 1995;Gertz et al, 1995).…”