Transplantation for ultra high-risk neuroblastoma patients: effect of tandem autologous stem cell transplantation

Year 2021, Volume: 4 Issue: 6, 943 - 948, 24.09.2021

Ebru Yılmaz Muhammed Bahadır Samur Alper Özcan Ekrem Ünal Musa Karakükçü

https://doi.org/10.32322/jhsm.985592

Cited By: 1

Abstract

Aim: Neuroblastoma is a tumor with a high mortality rate originating from primitive sympathetic ganglion cells. In recent years, the definition of "ultra high-risk" has been used, in which the response to treatment is added in addition to the disease characteristics. In this study, the results of tandem high-dose Iodine 131 (131I) metaiodobenzylguanidine (MIBG) and tandem autologous hematopoietic stem cell transplantation (HSCT) in patients who were diagnosed as refractory after first-line treatments and considered with ultra-high risk nöroblastom (NBL) in Erciyes University Medical Faculty Pediatric Bone Marrow Transplant Center were shared.
Material and Method: Eleven patients who underwent tandem MIBG and autologous HSCT with the diagnosis of refractory/ultra high-risk NBL between 2011 and 2021 were included in the study. Patient's data were obtained retrospectively using an electronic or manuscript medical record.
Results: Tandem autologous HSCT and MIBG treatment were applied to 11 patients with a median age of 40.5 months who were diagnosed with refractory/ultra high-risk neuroblastoma. In our study, the overall survival rate was 54.5% and event-free survival (EFS) was 39% at a median follow-up of 20.7 (7.8-105.6) months. Of the 6 surviving patients, 4 are followed in complete remission and 2 in partial remission.
Conclusion: Our study is the only study that includes a group of patients who received tandem high-dose MIBG and tandem autologous HSCT transplantation in refractory NBL patients without cytokine and immunotherapy. Tandem transplantation and MIBG therapy in ultra-high-risk NBL cases remain promising with acceptable toxicity. Adding immunotherapy to this treatment protocol and combining it with new treatment modalities such as anaplastic lymphoma kinase (ALK), which also takes into account genetic characteristics, may increase survival and event-free survival rates.

Keywords

neuroblastoma, tandem stem cell transplantation, children, tandem MIBG

Supporting Institution

Yok

Project Number

Yok

Thanks

The authors thank Prof. Dr Mehmet Akif Özdemir, Prof. Dr. Türkan Patıroğlu for their valuable contributions to the study.

References

• Swift CC, Eklund MJ, Kraveka JM, Alazraki AL. Updates in Diagnosis, Management, and Treatment of Neuroblastoma. Radiographics 2018; 38: 566-80.
• Schwab M, Shimada H, Joshi V, Brodeur GM. Neuroblastic tumours of adrenal gland and sympathetic nervous system. In: Pathology and Genetics. Tumours of the Nervous system, Kleihues P, Cavenee WK (eds). IARC Press: Lyon; 2000: 153-61.
• Smith V, Foster J. High-risk neuroblastoma treatment review. Children (Basel) 2018; 5: 114. 
• Almandoz JP, Xie L, Schellinger JN, et al. Impact of COVID-19 stay-at-home orders on weight-related behaviours among patients with obesity. Clin Obes 2020; 10: e12386.
• Kebudi R. Turkish Pediatric Oncology Group. Pediatric oncology in Turkey. J Pediatr Hematol Oncol 2012; 34: S12-4. 
• Louis CU, Shohet JM. Neuroblastoma: molecular pathogenesis and therapy. Annu Rev Med 2015; 66: 49-63.
• Zhang Y, Huang D, Zhang W, et al. Clinical characteristics of infant neuroblastoma and a summary of treatment outcome. Oncol Lett 2016; 12: 5356-62.
• Park JR, Kreissman SG, London WB, et al. Effect of tandem autologous stem cell transplant vs single transplant on event-free survival in patients with high-risk neuroblastoma: a randomized clinical trial. Jama 2019; 322: 746-55.
• Pinto NR, Applebaum MA, Volchenboum SL, et al. Advances in risk classification and treatment strategies for neuroblastoma. J Clin Oncol 2015; 33: 3008-17.
• Smith V, Foster J. High-risk neuroblastoma treatment review. Children (Basel) 2018; 5.
• Aygün Z, Batur Ş, Emre Ş, Celkan T, Özman O, Comunoglu N. Frequency of ALK and GD2 expression in neuroblastoma. Fetal Pediatr Pathol 2019; 38: 326-34.
• Morgenstern DA, Bagatell R, Cohn SL, et al. The challenge of defining "ultra-high-risk" neuroblastoma. Pediatr Blood Cancer 2019; 66: e27556.
• Berthold F, Spix C, Kaatsch P, Lampert F. Incidence, survival, and treatment of localized and metastatic neuroblastoma in Germany 1979-2015. Paediatr Drugs 2017; 19: 577-93.
• Park JR, Kreissman SG, London WB, et al. A phase III randomized clinical trial (RCT) of tandem myeloablative autologous stem cell transplant (ASCT) using peripheral blood stem cell (PBSC) as consolidation therapy for high-risk neuroblastoma (HR-NB): A Children's Oncology Group (COG) study.  J Clin Oncol 2016; 34.
• Kushner BH, Ostrovnaya I, Cheung IY, et al. Lack of survival advantage with autologous stem-cell transplantation in high-risk neuroblastoma consolidated by anti-GD2 immunotherapy and isotretinoin. Oncotarget 2016; 7: 4155.
• Kushner BH, Cheung NK, LaQuaglia MP, et al. International neuroblastoma staging system stage 1 neuroblastoma: a prospective study and literature review. J Clin Oncol 1996; 14: 2174-80. 
• Brodeur GM, Pritchard J, Berthold F, et al. Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol 1993; 11: 1466-77.
• Elborai Y, Hafez H, Moussa EA, et al. Comparison of toxicity following different conditioning regimens (busulfan/melphalan and carboplatin/etoposide/melphalan) for advanced stage neuroblastoma: Experience of two transplant centers. Pediatr Transplant 2016; 20(2): 284-9.
• Bansal D, Totadri S, Chinnaswamy G, et al. Management of neuroblastoma: ICMR consensus document. Indian J Pediatr 2017; 84: 446-55.
• Matthay KK, Tan JC, Villablanca JG, et al. Phase I dose escalation of iodine-131-metaiodobenzylguanidine with myeloablative chemotherapy and autologous stem-cell transplantation in refractory neuroblastoma: a new approaches to Neuroblastoma Therapy Consortium Study. J Clin Oncol 2006; 24: 500-6.
• Qayed M, Chiang KY, Ricketts R, et al. Tandem stem cell rescue as consolidation therapy for high-risk neuroblastoma. Pediatr Blood Cancer 2012; 58: 448-52.
• Wawrzyniak-Dzierżek E, Gajek K, Rybka B, et al. Feasibility and safety of treosulfan, melphalan, and thiotepa-based megachemotherapy with autologous or allogeneic stem cell transplantation in heavily pretreated children with relapsed or refractory neuroblastoma. Biol Blood Marrow Transplant 2019; 25: 1792-7.
• Pasqualini C, Dufour C, Goma G, Raquin MA, Lapierre V, Valteau-Couanet D. Tandem high-dose chemotherapy with thiotepa and busulfan-melphalan and autologous stem cell transplantation in very high-risk neuroblastoma patients. Bone Marrow Transplant 2016; 51: 227-31. 
• Suh JK, Koh KN, Min SY, et al. Feasibility and effectiveness of treatment strategy of tandem high-dose chemotherapy and autologous stem cell transplantation in combination with 131 I-MIBG therapy for high-risk neuroblastoma. Pediatr Transplant 2020; 24: e13658.
• Lee JW, Lee S, Cho HW, et al. Incorporation of high-dose 131I-metaiodobenzylguanidine treatment into tandem high-dose chemotherapy and autologous stem cell transplantation for high-risk neuroblastoma: results of the SMC NB-2009 study. J Hematol Oncol 2017; 10: 108.
• Sung KW, Son MH, Lee SH, et al. Tandem high-dose chemotherapy and autologous stem cell transplantation in patients with high-risk neuroblastoma: results of SMC NB-2004 study. Bone Marrow Transplant 2013; 48: 68-73. 
• George RE, Li S, Medeiros-Nancarrow C, et al. High-risk neuroblastoma treated with tandem autologous peripheral-blood stem cell-supported transplantation: long-term survival update. J Clin Oncol 2006; 24: 2891-6.
• Erbey F, Atay D, Akçay A, Öztürk G. Autologous cord blood transplantation in neuroblastoma. Turk J Pediatr 2015; 57: 210-1.
• Grupp SA, Asgharzadeh S, Yanik GA. Neuroblastoma: issues in transplantation. Biol Blood Marrow Transplant 2012; 18: S92-100.