Single and double high-dose chemotherapy with autologous stem cell transplantation in children with advanced solid tumours:: first experience

The disease-free survival of children with malignant disorders has increased impressively over the last three decades due to better understanding of tumour biology and the resultant improvement in diagnosis and therapy. Children with advanced and relapsed solid tumours, such as brain tumour, alveolar rhabdomyosarcoma, Ewing's sarcoma, or neuroblastoma, have not benefited from this progress. The concept of myeloablative high-dose chemotherapy (HDT) is based on the observation that certain cytostatic drugs have a steep linear dose-response curve, and thus escalating the dose may increase the tumour cell kill. The interest in HDT intensified when autologous stem cells mobilised from the peripheral blood became available, in view of the possibility of increasing the cell dose, which correlates directly with the time period of haematopoietic recovery and thus reduces therapy-associated toxicity. The aim of the study was to evaluate the feasibility of single or double HDT by autologous peripheral blood stem cell transplantation (PBSCT) after each cycle in children, and to obtain pilot data for future prospective clinical trials. 11 children aged between 2.8 and 17.2 years with brain tumours, soft tissue sarcomas, germ-cell tumours and neuroblastomas were analysed over a 2-year-period. 7 of the 11 children are in complete remission 2+ and 24+ months after HDT, 3 died of progressive disease and one child died of therapy-associated complications. The median hospital stay was 29.5 (22-104) days. An absolute neutrophil granulocyte count of 0.5x10(9)/l was achieved after a median stay of 11 days and a platelet count of >20 x 10(9)/l independent of platelet transfusions was achieved after 11 days. Painful stomatitis leading to total parenteral nutrition (9 children) and intravenous morphine therapy (6 children) was the most serious toxicity. Single or double HDT with autologous PBSCT after each cycle is feasible in children and offers basic data for conducting phase III paediatric clinical studies.