Autologous Stem-Cell Transplantation for High-Risk Neuroblastoma: Historical and Critical Review

Abstract

Curing high-risk neuroblastoma (HR-NB) is a challenging endeavor, which involves the optimal application of several therapeutic modalities. Treatment intensity for cancer became highly appealing in the 1990s. Investigative trials assumed that tumor response correlated with the dosage or intensity of drug(s) administered, and that this response would translate into improved survival. It was postulated that, if myelotoxicity could be reversed by stem-cell rescue, cure might be possible by increasing the dose intensity of treatment. The principle supported autologous stem-cell transplant (ASCT) strategies. High-dose therapy transformed clinical practice, legislation, and public health policy, and it drove a two-decade period of entrepreneurial oncology. However, today, no ASCT strategies remain for any solid tumor indication in adults. As with most solid malignancies, higher dosing of cytotoxic agents has not resulted in a clear benefit in survival for HR-NB patients, whereas the long-term toxicity has been well defined. Fortunately, novel approaches such as anti-GD2 immunotherapy have demonstrated a significant survival benefit with a much less adverse impact on the patient’s wellbeing. On the basis of extensive experience, persisting with administering myeloablative chemotherapy as the standard to treat children with HR-NB is not consistent with the overall aim in pediatric oncology of curing with as little toxicity as possible.

MYCN Impact on High-Risk Neuroblastoma: From Diagnosis and Prognosis to Targeted Treatment

“…Unfortunately, chemotherapy has many side effects and, particularly, myelotoxicity has been evaluated as the most dose-limiting toxicity for chemotherapeutic agents [ 88 ]. For this reason, the possibility of rescuing the stem cells from the patient and performing autologous stem cell transplantation (ASCT) after high-dose treatment could highly impact therapy outcome [ 89 , 90 ]. Many studies demonstrated how single [ 56 , 91 ] or more recent tandem transplantation [ 92 ] post-chemotherapy can increase event-free survival compared to chemotherapy alone, having a particular impact on HR-NB patients’ outcome.…”

Long-term hematopoietic transfer of the anti-cancer and lifespan-extending capabilities of a genetically engineered blood system by transplantation of bone marrow mononuclear cells

“…HSC therapy for different diseases ( Hifumi et al, 2017 ; Morgan et al, 2017 ; Giannaccare et al, 2020 ; Wu et al, 2020 ) including cancer has been intensively explored and practiced such as leukemia and neuroblastoma ( Daver et al, 2020 ; Mora, 2022 ). Also, certain characteristics of the young mice could be transferred to old mice via heterochronic parabiosis or heterochronic transplantation ( Conboy et al, 2005 ; Das et al, 2019 ; Goodell and Rando, 2015 ; Kang et al, 2020 ).…”

Long-term Hematopoietic Transfer of the Anti-Cancer and Lifespan-Extending Capabilities of A Genetically Engineered Blood System by Transplantation of Bone Marrow Mononuclear Cells

“…Hematopoietic stem cell therapy for different diseases [47][48][49][50] including cancer has been intensively explored and practiced such as leukemia, and neuroblastoma, etc 51,52 . Also, certain characteristics of the young mice could be transferred to old mice via heterochronic parabiosis or heterochronic transplantation [53][54][55][56] .…”