Thiotepa–melphalan myeloablative therapy for high‐risk neuroblastoma

Abstract

Background Appropriate high‐dose chemotherapy (HDC) for high‐risk neuroblastoma has not yet been established. In Japan, a unique HDC regimen that comprises two cycles of a total of 800 mg/m2 of thiotepa and a total of 280 mg/m2 of melphalan is widely utilized. Methods To evaluate the safety and efficacy of this thiotepa–melphalan high‐dose therapy for high‐risk neuroblastoma, we reviewed the medical records of 41 patients with high‐risk neuroblastoma who underwent this regimen followed by autologous peripheral blood stem cell rescue between 2002 and 2012. MYCN‐amplified high‐risk neuroblastomas were observed in 23 patients. All patients underwent intensive multidrug induction chemotherapy, but none underwent anti‐GD2 antibody immunotherapy. The primary tumor was resected at the adequate time point. Results The median follow‐up duration for living patients was 9.2 years (range 5.5–14.0 years). The 5‐year event‐free survival (EFS) and overall survival from treatment initiation were 41.5 ± 7.7% and 56.1 ± 7.8%, respectively. The 5‐year EFS of MYCN‐amplified high‐risk neuroblastoma patients was 60.9 ± 10.2%, which was significantly superior compared with those with MYCN‐nonamplified high‐risk neuroblastoma (16.7 ± 8.8%; p < .001). MYCN amplification was the most favorable prognostic factor for EFS (hazard ratio = 0.29; 95% confidence interval = 0.12–0.66). Of the 41 patients, three died because of regimen‐related toxicity (infection, n = 2; microangiopathy, n = 1). Conclusion The thiotepa–melphalan high‐dose therapy with thiotepa and melphalan may be effective for high‐risk neuroblastoma. However, this regimen is toxic and warrants special attention in clinical practice.

Oral Metronomic Maintenance Therapy Can Improve Survival in High-Risk Neuroblastoma Patients Not Treated with ASCT or Anti-GD2 Antibodies

“…But, inferior EFS and OS in high-risk NB patients with MYCN amplification have been reported from the COG and other studies [ 25 , 26 , 27 , 28 ]. One study from Japan showed MYCN amplification was the most favorable prognostic factor for EFS of high-risk NB [ 29 ]. Our results showed that the patients with MYCN amplified had worse the EFS and OS rates than those without MYCN amplified in high-risk NB.…”

To transplant, or not to transplant? That is the question. A patient advocate evaluation of autologous stem cell transplant in neuroblastoma

“…Cheung and colleagues raised several points in contention: OS with long follow‐up may be more indicative of cure than EFS when including post‐relapse patients; frequent testing of nontransplant patients may mean relapses are more readily detectable when localized and amenable to salvage therapies; evidence from prior decades may not be retained in the contemporary era of immunotherapy; and a high prevalence of late effects. Debate regarding the merits of transplant has continued to persist, most recently when an analysis of 41 patients who underwent ASCT using thiotepa‐melphalan at three institutions in Japan prompted Kushner to respond questioning both the study and wider evidence for continued use of ASCT in the modern era 29,30 …”

The impact of response to induction chemotherapy on the event-free and overall survival in patients with high-risk neuroblastoma: a systematic review and meta-analysis

“…И хотя другие исследования, представленные в нашем анализе, продемонстрировали выраженное влияние ответа на индукцию на выживаемость, часть из них была ограничена небольшим объемом выборки и коротким периодом наблюдения [20,22]. В исследовании F. Yamazaki и соавт.…”

“…В исследовании F. Yamazaki и соавт. из Японии показано значительное повышение БСВ и ОВ у пациентов, достигших CR/VGPR/ PR в конце индукции, и эта разница была еще более очевидной в подгруппе пациентов с CR/VGPR против худшего ответа (5-летняя БСВ 78,6 ± 11,0% против 22,2 ± 8,0%; p = 0,00041 и 5-летняя ОВ 92,9 ± 6,9% против 37,0 ± 9,3%; p = 0,00019) [22]. Также влияние лучшего ответа на индукцию на более высокие показатели долгосрочной выживаемости сохранялась у пациентов с наличием амплификации гена MYCN при проведении подгруппового анализа.…”