Treatment of high-risk solid tumors of childhood with intensive therapy and autologous bone marrow transplantation.

Autologous bone marrow transplantation (ABMT) allows delivery of intensive, marrow-ablative chemotherapy or chemoradiotherapy to children with high-risk solid tumors. Results from several studies of neuroblastoma suggest that outcome is improved by ABMT; however, relapses can occur months to years after complete clinical remission. Other high-risk tumors including peripheral neuroepithelioma, Ewing's sarcoma, rhabdomyosarcoma, Wilms' tumor, and brain tumors also appear to be responsive to intensive marrow-ablative therapy, although few studies have been reported. For tumors that can metastasize to marrow, a sensitive method is necessary for detecting tumor cell contamination. Immunocytologic analysis with monoclonal antibodies can identify one neuroblastoma cell per 10(5) normal marrow cells; this method also is applicable to other tumors with appropriate antibodies. Ex vivo removal (purging) of tumor cells decreases the probability of infusing tumorigenic cells with the ABMT. There is considerable experience in tumor detection and purging for neuroblastoma, but little has been done for other childhood solid tumors. Future investigations of ABMT will aim to further increase disease-free survival by intensifying induction and marrow-ablative regimens and by developing therapies to be given after ABMT that are directed at minimal residual disease. As pilot investigations mature, the efficacy of ABMT and conventional chemotherapy will be compared in multi-institution randomized studies.