Haema 2013; 4(3):263-274
by Vassilios Papadakis1, Georgia Avgerinou2
1Pediatrician – Haematologist, Director NHS,
2Haematologist University Scholar, Cancer Unit “Marianna V. Vardinogianni – ELPIDA”, Department of Pediatric Haematology – Oncology, Children Hospital “Agia Sofia”, Athens, Greece
Abstract
Over the last decades, advances in the treatment of pediatric cancers have increased cure rates, but children with metastatic or recurrent solid tumors have dismal prognosis despite initial transient responses to therapy. Steep dose-response relationship has been observed with many chemotherapeutic agents. In an effort to overcome resistance and improve cure rates, high dose therapy with autologous hematopoietic stem cell support (ASCT) has been applied in high risk patients. Most published experience consists of retrospective, or single-arm prospective studies; while randomized clinical trials are limited, due in part to the rarity of pediatric cancers treatable by ASCT. International cooperation is needed and it is emerging. ASCT has improved outcomes in patients with metastatic neuroblastoma with refinements in the preparative regimens, and there is substantial evidence to also expect improvements in patients with Ewing sarcoma, germ cell tumors and some subtypes of central nervous system malignancies. ASCT is also frequently used to treat patients with other high-risk solid tumors such as osteosarcoma, rhabdomyosarcoma, Wilms’ tumor, retinoblastoma and brain tumors. Published literature demonstrates that high dose therapy in these tumors results in equivalent or superior outcomes when compared with conventional therapies. However, patient selection and heterogeneity, graft characteristics and processing and the varied conditioning regimens pose difficulties in extracting solid conclusions. Most importantly, all studies clearly demonstrate a marked decrease in regimen-related toxicities over time. Thus, the vast majority of treatment failures are now due to disease recurrence. Recent progress in elucidating disease specific markers, genetic and signaling pathways with parallel development of targeted therapies and immunotherapies necessitates large prospective clinical trials, in order to identify the role and usefulness of each treatment modality in improving patient outcome, with the least possible acute and long-term toxicity. Meanwhile, a large proportion of patients with high risk solid tumors will undergo ASCT in an effort to improve patients’ outcome.