Abstract
A group of 12 children with advanced neuroblastoma (7 Stage IV and 5 Stage III), selected by their initial response to chemotherapy with pulsed cyclophosphamide/vincristine/Adriamycin (CVA), were given consolidation therapy with high-dose melphalan (140 mg/m2) and then surgical removal of residual disease. Twenty-two high-dose melphalan procedures were combined with autologous marrow grafting to offset myelotoxicity and were well tolerated. In each of 2 additional children, procedures carried out without marrow autografting led to serious marrow and mucosal toxicity. There were no treatment-related deaths. In 7/11 patients with evaluable computerized tomographic (CT) scans there was a decrease in maximum diameter of the primary tumour after melphalan. Complete response was achieved in 6 patients, of whom 3 are well and have no evidence of disease at 35, 33 and 18 months from completion of all treatment; however, although survival (median 23 months) of all 12 autografted patients is longer than that of 28 comparable children treated between 1970-77 with conventional chemotherapy (median 14 months) the difference is not statistically significant. High-dose melphalan is a safe and tolerable treatment in children when combined with autologous marrow grafting, but further study is required to determine whether the procedure can improve prognosis for patients with advanced neuroblastoma.
Highlights
Summary.-A group of 12 children with advanced neuroblastoma (7 Stage IV and 5 Stage III), selected by their initial response to chemotherapy with pulsed cyclophosphamide/vincristine/Adriamycin (CVA), were given consolidation therapy with high-dose melphalan (140 mg/M2) and surgical removal of residual disease
Tumours, reported 2-year survival figures vary more, but in no series exceed 50 %; our own experience is that Stage III patients with unresectable primary disease fare just as badly as those with Stage IV disease (Ninane et al, 1981)
Between 1977 and 1979, in an attempt to improve the prognosis for children with advanced neuroblastoma, we studied the effect of high-dose melphalan (HDM) chemotherapy in 14 patients with Stage III or IV disease who had undergone "induction" chemotherapy with cyclophosphamide, vincristine and Adriamycin (CVA)
Summary
Diagnosis and staging.-In each of the patients (Table I), a diagnosis of neuroblastoma was established by either (a) tissue biopsy or (b) significantly elevated 24h urinary vanillyl-mandelic acid (VMA) excretion and cytological evidence of marrow infiltration by tumour cells. Surgery was eventually performed in 10 patients and yielded histological confirmation in 9 of them. Staging investigations included full blood count, chest X-rays, IVU, skeletal survey, liver and bone radioisotope scans, and marrow aspirates and/or trephine biopsies from at least 2 sites. Computerized tomography (CT) and ultrasound examinations were used serially to assess the size of the primary tumours. In 5 patients, lymph nodes were involved; because most of the primary tumours were abdominal and since
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