High-dose chemotherapy and autologous haematopoietic stem cell rescue for children with high-risk neuroblastoma

Background Despite the development of new treatment options, the prognosis of high-risk neuroblastoma patients is still poor; more than half of patients experience disease recurrence. High-dose chemotherapy and haematopoietic stem cell rescue (i.e. myeloablative therapy) might improve survival. Objectives To compare the effectiveness of myeloablative therapy with conventional therapy in children with high-risk neuroblastoma. Search strategy We searched CENTRAL (The Cochrane Library 2009, issue 1), MEDLINE/PubMed (1966 to January 2009) and EMBASE/Ovid (1980 to January 2009). In addition, we searched reference lists of relevant articles, conference proceedings and ongoing trial databases. Selection criteria Randomised controlled trials (RCTs) comparing the effectiveness of myeloablative therapy with conventional therapy in high-risk neuroblastoma patients. Data collection and analysis Two authors independently performed study selection, data extraction and risk of bias assessment. If possible, we pooled results. Main results We identified three RCTs including 739 children. The meta-analysis of event-free survival showed a significant difference in favour of the myeloablative therapy group (HR 0.78; 95% CI 0.67 to 0.90), as did the meta-analysis of overall survival (HR 0.74; 95% CI 0.57 to 0.98). The meta-analysis of secondary malignant disease and treatment-related death did not show a significant difference between the treatment groups. In one study a significant difference in favour of the conventional therapy group was identified for renal effects, interstitial pneumonitis and veno-occlusive disease, whereas for serious infections and sepsis no significant difference between the treatment groups was identified. In the individual studies we evaluated different subgroups, but the results were not univocal in all studies. All studies had some methodological limitations. Authors' conclusions Based on the currently available evidence, myeloablative therapy seems to be a good treatment option for children with high-risk neuroblastoma. It results in higher survival rates than conventional therapy, although possible higher levels of adverse effects should be kept in mind. A definitive conclusion regarding the effect of myeloablative therapy in different subgroups is not possible. This systematic review only allows a conclusion on the concept of myeloablative therapy; no conclusions can be made regarding the best treatment strategy. Future trials on the use of myeloablative therapy for high-risk neuroblastoma should focus on identifying the most optimal induction and/or myeloablative regimen. The best study design to answer these questions is a RCT. These RCTs should be performed in homogeneous study populations (for example, regarding stage of disease and patient age) and have a long-term follow up. Different risk groups should be taken into account.