rating new chemotherapeutic agents, targeted radiotherapy with 131I-anti-GD2 (Cheung and Miraldi 1988) 131I-MIBG (Mastrangelo et al. 2001), or biologic therapies.

Peripheral blood stem cell harvest can be performed as soon as clearance of circulating tumor cells and reduction of bone marrow tumor has been achieved. The optimal timing with respect to minimal residual disease (MRD) has not yet been determined, but in practice, a harvest after only two to three cycles has been shown to eliminate circulating tumor cells (Seeger et al. 2000) and results in tumorfree peripheral blood stem cells down to a sensitivity of 1 tumor cell per 100,000 in almost all cases (Kreiss-man et al. 2000). Quantitative studies suggest that tumor content in the blood is 100-fold less than that of marrow, and if marrow is negative for tumor by im-munocytology (<1/106), peripheral blood contamination is generally <1/108 (Faulkner et al. 2000). While rare tumor cells may continue to be present by sensitive testing methods, such as immunocytology and RT-PCR (Burchill et al. 2001; Cheung et al. 2003), the ability of these rare cells to cause relapse after infusion is unknown. An ongoing randomized Children's Oncology Group study of stem cell purging with measurement of MRD in stem cell products and serial samples of peripheral blood and bone marrow by immunocytology and RT-PCR may help to resolve this question. Harvesting stem cells earlier in induction rather than later permits a better collection of

CD34 cells, before stem cells have been depleted by repeated courses of intensive chemotherapy,but risks contamination by tumor cells.

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