Early and late relapse continue to occur at a high rate, although the newer, dose-intensive induction and myeloablative therapies have considerably prolonged survival and improved EFS (Matthay et al. 1999). Relapse is most common in bone and bone marrow, and sites of hypoxic and microscopic residual disease (DuBois et al. 1999). For this reason it has become increasingly important to find new approaches to eliminate minimal residual disease with agents that will be tolerable following myeloablative therapy, when disease is likely to be minimal. This provides the ideal window of time to eradicate resistant clones that are still present using novel therapies not dependent upon standard cytotoxic mechanisms (see Chaps. 14-16); these include differentiating agents such as 13-ris-retinoic acid (Matthay et al. 1999), fenretinide (Delia et al. 1993; Maurer et al. 1999; Garaventa et al. 2003; Basniewski et al. 1999), anti-GD2 monoclonal antibodies (Ozkaynac et al. 2000), immunocytokines (Lode et al. 1997), genetically engineered vaccines (Bowman et al. 1998; Davidoff et al. 1999), anti-an-
giogenic therapy (Stern et al. 2001), small molecule inhibitors of tyrosine kinase genes (Evans et al. 1999; Smith et al. 2004), or histone deacetylase inhibitors (Huang et al. 2002).
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