Secondary malignant neoplasms after high‐dose chemotherapy and autologous stem cell rescue for high‐risk neuroblastoma

Abstract

Background Outcomes for high‐risk neuroblastoma remain poor. Modern treatment protocols utilizing intense induction followed by myeloablative consolidation chemotherapy with autologous stem cell rescue (ASCR) have improved survival rates, but the long‐term sequelae, including development of secondary malignant neoplasms (SMN), are just now surfacing. Methods We retrospectively reviewed data from 87 patients with high‐risk neuroblastoma who were treated with intensive induction chemotherapy followed by ASCR between January 1991 and July 2011 following one of two institutional protocols: Chicago Pilot 1 (CP1; n = 12) and Chicago Pilot 2 (CP2; n = 75). Results The 15‐year overall survival rate for all 87 patients was 33.9% (95% confidence interval [CI], 23.1–45.0%). The 10‐ and 15‐year cumulative incidence of SMN was 16.5% (95%CI, 7.2–38.0%) and 34.2% (95%CI, 18.6–63.1%), respectively, without evidence of a plateau at 15 years. Six of the 10 patients (n = 2 in CP1 and n = 8 in CP2) who developed SMN had hematologic malignancies including acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS). Solid tumors included thyroid papillary carcinoma, chondrosarcoma, hepatocellular carcinoma, and biliary adenocarcinoma. Conclusion A significantly higher incidence of SMN, especially hematological malignancies, was observed in this cohort compared to older neuroblastoma studies, potentially due to exposure to epipodophyllotoxins and a high cumulative dose of alkylating agents these patients received. The risk of developing an SMN continued to increase with survival time and did not reach the plateau at 15 years. Although the number of the patients is relatively small, our study emphasizes the need for life‐long follow‐up of survivors who were treated using modern therapy. Pediatr Blood Cancer 2014; 61:1350–1356. © 2014 Wiley Periodicals, Inc.

Second cancer risk in childhood cancer survivors treated with intensity‐modulated radiation therapy (IMRT)

“…However, the latter is most relevant with regard to RT exposure. The two cases of MDS are assumed to be related to the intensive chemotherapy administered for high‐risk neuroblastoma, which is reported to convey a risk of MDS and acute myelogenous leukemia as high as 34% .…”

Treatment and outcome of neuroblastoma with intraspinal extension: A systematic review

“…7 Chemotherapy does not lead to immediate relief of spinal cord compression; however, the therapeutic time window seems to extend beyond the first hours of paralysis. 9 Second malignant neoplasms, especially after highdose regimens, [22][23][24] ototoxicity as a consequence of platinum-based antineoplastic drug administration, [25][26][27] and anthracycline-induced cardiotoxicity [28][29][30] are some of the well-documented long-term health problems encountered after chemotherapy.…”

Overview and recent advances in the treatment of neuroblastoma

“…Between 2% and 7% of neuroblastoma survivors develop a second malignancy as a result of their therapy, with a cumulative 30-year incidence for high-risk patients of approximately 10% [170][171][172]. High-risk therapy, in particular, contains several known risk factors for secondary malignancies, including alkylating agents, topoisomerase II inhibitors, platinum compounds, and radiotherapy.…”