Patients with disseminated neuroblastoma are considered a poor-risk category, hence, our approach towards their treatment should be reconsidered in terms of the-unique clinical and biological characteristics of neuroblastoma tumor growth. To this end, we have devised a treatment program consisting of surgery, and a schedule of sequentially escalating doses of cyclophosphamide combined with other drugs until a minimal disease status is obtained. When this is achieved, the patient is treated with maximal therapy, i.e., total body irradiation, high-dose L-phenylalanine mustard and dianhydrogalactitol followed by reconstitution with an autologous bone marrow graft. Details of this program include problems associated with evaluation of response, i.e., evaluation of risk, determination of minimal tumor burden, avoidance of toxicity, and compensation for supportive measures during maximal therapy. Additional problems of purging bone marrow of tumor cells are considered.