Abstract
Increasing treatment intensity has improved outcomes for children with neuroblastoma. We performed a pilot study in the Children’s Oncology Group to assess the feasibility and toxicity of a tandem myeloablative regimen without TBI supported by autologous CD34-selected peripheral blood stem cells. Forty-one patients with high-risk neuroblastoma were enrolled; eight patients did not receive any myeloablative consolidation procedure and seven received only one. Two patients out of 41 (4.9%) experienced transplant-related mortality. CD34 selection was discontinued after subjects were enrolled due to serious viral illness. From the time of study enrollment, the overall 3-year EFS and OS were 44.8±9.6% and 59.2±9.2% (N=41). These results demonstrate that tandem transplantation in the cooperative group setting is feasible and support a randomized comparison of single vs tandem myeloablative consolidation with PBSC support for high-risk neuroblastoma.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Maris JM, Hogarty MD, Bagatell R, Cohn SL . Neuroblastoma. Lancet 2007; 369: 2106–2120.
Cheung NV, Heller G . Chemotherapy dose intensity correlates strongly with response, median survival, and median progression-free survival in metastatic neuroblastoma. J Clin Oncol 1991; 9: 1050–1058.
Matthay KK, Villablanca JG, Seeger RC, Stram DO, Harris RE, Ramsay NK et al. Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. Children's Cancer Group. N Engl J Med 1999; 341: 1165–1173.
Berthold F, Boos J, Burdach S, Erttmann R, Henze G, Hermann J et al. Myeloablative megatherapy with autologous stem-cell rescue versus oral maintenance chemotherapy as consolidation treatment in patients with high-risk neuroblastoma: a randomised controlled trial. Lancet Oncol 2005; 6: 649–658.
Kreissman SG, Rackoff W, Lee M, Breitfeld PP . High dose cyclophosphamide with carboplatin: a tolerable regimen suitable for dose intensification in children with solid tumors. J Pediatr Hematol Oncol 1997; 19: 309–132.
Kletzel M, Katzenstein HM, Haut PR, Yu AL, Morgan E, Reynolds M et al. Treatment of high-risk neuroblastoma with triple-tandem high-dose therapy and stem-cell rescue: results of the Chicago Pilot II Study. J Clin Oncol 2002; 20: 2284–2292.
Donovan J, Temel J, Zuckerman A, Gribben J, Fang J, Pierson G et al. CD34 selection as a stem cell purging strategy for neuroblastoma: preclinical and clinical studies. Med Pediatr Oncol 2000; 35: 677–682.
Kanold J, Berger M, Rapatel C, de Lumley L, Lutz P, Plantaz D et al. CD34+ cell immunoselection from G-CSF-alone-primed peripheral blood in children with low body mass. Br J Haematol 1995; 91: 431–433.
Kanold J, Yakouben K, Tchirkov A, Carret AS, Vannier JP, LeGall E et al. Long-term results of CD34(+) cell transplantation in children with neuroblastoma. Med Pediatr Oncol 2000; 35: 1–7.
Grupp SA, Stern JW, Bunin N, Nancarrow C, Ross AA, Mogul M et al. Tandem high-dose therapy in rapid sequence for children with high-risk neuroblastoma. J Clin Oncol 2000; 18: 2567–2575.
George RE, Li S, Medeiros-Nancarrow C, Neuberg D, Marcus K, Shamberger RC et al. High-risk neuroblastoma treated with tandem autologous peripheral-blood stem cell-supported transplantation: long-term survival update. J Clin Oncol 2006; 24: 2891–2896.
Hobbie WL, Moshang T, Carlson CA, Goldmuntz E, Sacks N, Goldfarb SB et al. Late effects in survivors of tandem peripheral blood stem cell transplant for high-risk neuroblastoma. Pediatr Blood Cancer 2008; 51: 679–683.
Granger M, Grupp SA, Kletzel M, Kretschmar C, Naranjo A, London WB et al. Feasibility of a tandem autologous peripheral blood stem cell transplant regimen for high risk neuroblastoma in a cooperative group setting: a Pediatric Oncology Group study: a Report from the Children's Oncology Group. Pediatr Blood Cancer 2012.
Brodeur GM, Pritchard J, Berthold F, Carlsen NL, Castel V, Castelberry RP et al. Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol 1993; 11: 1466–1477.
Marabelle A, Merlin E, Halle P, Paillard C, Berger M, Tchirkov A et al. CD34+ immunoselection of autologous grafts for the treatment of high-risk neuroblastoma. Pediatr Blood Cancer 2011; 56: 134–142.
Powell JL, Bunin NJ, Callahan C, Aplenc R, Griffin G, Grupp SA . An unexpectedly high incidence of Epstein-Barr virus lymphoproliferative disease after CD34+ selected autologous peripheral blood stem cell transplant in neuroblastoma. Bone Marrow Transplant 2004; 33: 651–657.
Kaplan EL, Meier P . Non-parametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.
Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples. Br J Cancer 1977; 35: 1–39.
Yu AL, Gilman AL, Ozkaynak MF, London WB, Kreissman SG, Chen HX et al. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med 2010; 363: 1324–1334.
Flandin I, Hartmann O, Michon J, Pinkerton R, Coze C, Stephan JL et al. Impact of TBI on late effects in children treated by megatherapy for stage IV neuroblastoma. A study of the French Society of Pediatric oncology. Int J Radiat Oncol Biol Phys 2006; 64: 1424–1431.
Ladenstein R, Potschger U, Hartman O, Pearson AD, Klingebiel T, Castel V et al. 28 years of high-dose therapy and SCT for neuroblastoma in Europe: lessons from more than 4000 procedures. Bone Marrow Transplant 2008; 41 (Suppl 2): S118–S127.
Qayed M, Chiang KY, Ricketts R, Alazraki A, Tahvildari A, Haight A et al. Tandem stem cell rescue as consolidation therapy for high-risk neuroblastoma. Pediatr Blood Cancer 2011; 58: 448–452.
Kramer K, Kushner B, Heller G, Cheung NK . Neuroblastoma metastatic to the central nervous system. The Memorial Sloan-kettering Cancer Center Experience and A Literature Review. Cancer 2001; 91: 1510–1519.
Pradhan KR, Johnson CS, Vik TA, Sender LS, Kreissman SG . A novel intensive induction therapy for high-risk neuroblastoma utilizing sequential peripheral blood stem cell collection and infusion as hematopoietic support. Pediatr Blood Cancer 2005.
Zage PE, Kletzel M, Murray K, Marcus R, Castleberry R, Zhang Y et al. Outcomes of the POG 9340/9341/9342 trials for children with high-risk neuroblastoma: a report from the Children's Oncology Group. Pediatr Blood Cancer 2008; 51: 747–753.
Kreissman SG, Villablanca JG, Seeger RC, Grupp SA, London WB, Maris JM et al. A randomized phase III trial of myeloablative autologous peripheral blood stem cell (PBSC) transplant for high-risk neuroblastoma (HR-NB) employing immunomagnetic purged versus unpurged PBSC: A Children’s Oncology Group study. J Clin Oncol 2008; 26 (suppl) abstr 10011.
Barrett D, Fish JD, Grupp SA . Autologous and allogeneic cellular therapies for high-risk pediatric solid tumors. Pediatr Clin North Am 2010; 57: 47–66.
Gross TG, Steinbuch M, DeFor T, Shapiro RS, McGlave P, Ramsay NK et al. B cell lymphoproliferative disorders following hematopoietic stem cell transplantation: risk factors, treatment and outcome. Bone Marrow Transplant 1999; 23: 251–258.
Peniket AJ, Perry AR, Williams CD, MacMillan A, Watts MJ, Isaacson PG et al. A case of EBV-associated lymphoproliferative disease following high-dose therapy and CD34-purified autologous peripheral blood progenitor cell transplantation. Bone Marrow Transplant 1998; 22: 307–309.
Lones MA, Kirov I, Said JW, Shintaku IP, Neudorf S . Post-transplant lymphoproliferative disorder after autologous peripheral stem cell transplantation in a pediatric patient. Bone Marrow Transplant 2000; 26: 1021–1024.
Mackall CL, Fleisher TA, Brown MR, Magrath IT, Shad AT, Horowitz ME et al. Lymphocyte depletion during treatment with intensive chemotherapy for cancer. Blood 1994; 84: 2221–2228.
Mackall CL, Stein D, Fleisher TA, Brown MR, Hakim FT, Bare CV et al. Prolonged CD4 depletion after sequential autologous peripheral blood progenitor cell infusions in children and young adults. Blood 2000; 96: 754–762.
Fish JD, Grupp SA . Stem cell transplantation for neuroblastoma. Bone Marrow Transplant 2008; 41: 159–165.
Acknowledgements
Supported in part by the WW Smith Charitable Trust, and the Foerderer-Murray, Weinberg and Sanford Funds of the Children’s Hospital of Philadelphia (S.A. Grupp); the Robert A. Good/ASBMT New Investigator Award (A.E. Seif); NIH grants U10 CA98413 (COG SDC grant) and U10 CA98543 (COG Chair’s grant). We would also like to thank Danniel Gaidula, MFA, for assistance in preparing Figure 1.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Seif, A., Naranjo, A., Baker, D. et al. A pilot study of tandem high-dose chemotherapy with stem cell rescue as consolidation for high-risk neuroblastoma: Children’s Oncology Group study ANBL00P1. Bone Marrow Transplant 48, 947–952 (2013). https://doi.org/10.1038/bmt.2012.276
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/bmt.2012.276
Keywords
This article is cited by
-
Significance of hematopoietic surface antigen CD34 in neuroblastoma prognosis and the genetic landscape of CD34-expressing neuroblastoma CSCs
Cell Biology and Toxicology (2021)
-
Veno-occlusive disease after high-dose busulfan–melphalan in neuroblastoma
Bone Marrow Transplantation (2020)
-
Neuroblastoma: clinical and biological approach to risk stratification and treatment
Cell and Tissue Research (2018)
-
Toxicities of busulfan/melphalan versus carboplatin/etoposide/melphalan for high-dose chemotherapy with stem cell rescue for high-risk neuroblastoma
Bone Marrow Transplantation (2016)
-
Tandem high-dose chemotherapy with thiotepa and busulfan–melphalan and autologous stem cell transplantation in very high-risk neuroblastoma patients
Bone Marrow Transplantation (2016)