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In Vivo Cytoreduction Studies and Cell Sorting–Enhanced Tumor-Cell Detection in High-Risk Neuroblastoma Patients: Implications for Leukapheresis Strategies

From the Hematology-Oncology Service, Department of Pediatrics, University of Florence, Ospedale Pediatrico A. Meyer, Florence, and Oncology Service, Istituto G. Gaslini, Genoa, Italy.

Address reprint requests to Lawrence B. Faulkner, MD, Sezione di Oncoematologia, Ospedale Meyer, Via L. Giordano 13, 50132 Firenze, Italy; email l.faulkner{at}ao-meyer.toscana.it

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.

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