In vivo cytoreduction studies and cell sorting-enhanced tumor-cell detection in high-risk neuroblastoma patients: Implications for leukapheresis strategies

Lawrence B. Faulkner, Alberto Garaventa, Antonella Paoli, Veronica Tintori, Angela Tamburini, Laura Lacitignola, Marinella Veltroni, Maria Serena Lo Piccolo, Elisabetta Viscardi, Claudia Milanaccio, Annalisa Tondo, Serena Spinelli, Gabriella Bernini, Bruno De Bernardi

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Abstract

Purpose: To improve autologous leukapheresis strategies in high-risk neuroblastoma (NB) patients with extensive bone marrow involvement at diagnosis. Patients and Methods: Anti-G(D2) immunocytochemistry (sensitivity, 1 in 105 to 106 leukocytes) was used to evaluate blood and bone marrow disease at diagnosis and during the recovery phase of the first six chemotherapy cycles in 57 patients with stage 4 NB and bone marrow disease at diagnosis. A total of 42 leukapheresis samples from the same patients were evaluated with immunocytology, and in 24 of these patients, an anti-G(D2) immunomagnetic enrichment step was used to enhance tumor-cell detection. Results: Tumor cytoreduction was much faster in blood compared with bone marrow (3.2 logs after the first cycle and 2.1 logs after the first two cycles, respectively). Bone marrow disease was often detectable throughout induction, with a trend to plateau after the fourth cycle. By direct anti-G(D2) immunocytology, a positive leukapheresis sample was obtained in 7% of patients after either the fifth or sixth cycle; when NB cell immunomagnetic enrichment was applied, 25% of patients had a positive leukapheresis sample (sensitivity, 1 in 107 to 108 leukocytes). Conclusion: Standard chemotherapy seems to deliver most of its in vivo purging effect within the first four cycles. In patients with overt marrow disease at diagnosis, postponing hematopoietic stem-cell collection beyond this point may not be justified. Tumor-cell clearance in blood seems to be quite rapid, and earlier collections via peripheral-blood leukapheresis might be feasible. Immunomagnetically enhanced NB cell detection can be highly sensitive and can indicate whether ex vivo purging should be considered. (C) 2000 by American Society of Clinical Oncology.

Original languageEnglish
Pages (from-to)3829-3836
Number of pages8
JournalJournal of Clinical Oncology
Volume18
Issue number22
Publication statusPublished - Nov 15 2000

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Faulkner, L. B., Garaventa, A., Paoli, A., Tintori, V., Tamburini, A., Lacitignola, L., Veltroni, M., Lo Piccolo, M. S., Viscardi, E., Milanaccio, C., Tondo, A., Spinelli, S., Bernini, G., & De Bernardi, B. (2000). In vivo cytoreduction studies and cell sorting-enhanced tumor-cell detection in high-risk neuroblastoma patients: Implications for leukapheresis strategies. Journal of Clinical Oncology, 18(22), 3829-3836.