Haploidentical Stem Cell Transplantation in Neuroblastoma

Summary

Children with primary resistant or relapsed neuroblastoma who do not achieve remission with conventional chemotherapy have extremely dismal prognosis. A novel treatment strategy combining tumor targeted radioisotope treatment with metaiodobenzylguanidine (MIBG) and immunotherapeutic effect of haploidentical stem cell transplantation (haploSCT) followed by low-dose donor lymphocyte infusions will be piloted. The use of the isotope is aimed to decrease pre-transplant tumour burden. Reduced intensity conditioning containing Fludarabine, Thiotepa and Melfalan will enable sustained engraftment as well as will serve as additional anti-tumor treatment. A prompt natural killer (NK)-cell mediated tumour control may be achieved by haploidentical stem cell transplantation. The investigators hypothesize that tumour cells potentially evading NK-cell mediated immunity may be targeted by infused donor T-cells and eliminated by either MHC-dependent manner or through a bystander effect. The possible graft versus tumor effect will be evaluated in children with therapy resistant neuroblastoma.

Timeline

Start

2005-08

Primary completion

2022-12-31

Completion

2022-12-31

Publications

• Background Inoue M, Nakano T, Yoneda A, Nishikawa M, Nakayama M, Yumura-Yagi K, Sakata N, Yasui M, Okamura T, Kawa K. Graft-versus-tumor effect in a patient with advanced neuroblastoma who received HLA haplo-identical bone marrow transplantation. Bone Marrow Transplant. 2003 Jul;32(1):103-6. doi: 10.1038/sj.bmt.1704070.
• Background Matthay KK, Tan JC, Villablanca JG, Yanik GA, Veatch J, Franc B, Twomey E, Horn B, Reynolds CP, Groshen S, Seeger RC, Maris JM. 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 Jan 20;24(3):500-6. doi: 10.1200/JCO.2005.03.6400.
• Background Prigione I, Corrias MV, Airoldi I, Raffaghello L, Morandi F, Bocca P, Cocco C, Ferrone S, Pistoia V. Immunogenicity of human neuroblastoma. Ann N Y Acad Sci. 2004 Dec;1028:69-80. doi: 10.1196/annals.1322.008.
• Background Neal ZC, Imboden M, Rakhmilevich AL, Kim KM, Hank JA, Surfus J, Dixon JR, Lode HN, Reisfeld RA, Gillies SD, Sondel PM. NXS2 murine neuroblastomas express increased levels of MHC class I antigens upon recurrence following NK-dependent immunotherapy. Cancer Immunol Immunother. 2004 Jan;53(1):41-52. doi: 10.1007/s00262-003-0435-2. Epub 2003 Sep 18.
• Background Raffaghello L, Prigione I, Bocca P, Morandi F, Camoriano M, Gambini C, Wang X, Ferrone S, Pistoia V. Multiple defects of the antigen-processing machinery components in human neuroblastoma: immunotherapeutic implications. Oncogene. 2005 Jul 7;24(29):4634-44. doi: 10.1038/sj.onc.1208594.
• Background Lang P, Pfeiffer M, Muller I, Schumm M, Ebinger M, Koscielniak E, Feuchtinger T, Foll J, Martin D, Handgretinger R. Haploidentical stem cell transplantation in patients with pediatric solid tumors: preliminary results of a pilot study and analysis of graft versus tumor effects. Klin Padiatr. 2006 Nov-Dec;218(6):321-6. doi: 10.1055/s-2006-942256.
• Results Toporski J, Garkavij M, Tennvall J, Ora I, Gleisner KS, Dykes JH, Lenhoff S, Juliusson G, Scheding S, Turkiewicz D, Bekassy AN. High-dose iodine-131-metaiodobenzylguanidine with haploidentical stem cell transplantation and posttransplant immunotherapy in children with relapsed/refractory neuroblastoma. Biol Blood Marrow Transplant. 2009 Sep;15(9):1077-85. doi: 10.1016/j.bbmt.2009.05.007. Epub 2009 Jul 8.
• Results Illhardt T, Toporski J, Feuchtinger T, Turkiewicz D, Teltschik HM, Ebinger M, Schwarze CP, Holzer U, Lode HN, Albert MH, Gruhn B, Urban C, Dykes JH, Teuffel O, Schumm M, Handgretinger R, Lang P. Haploidentical Stem Cell Transplantation for Refractory/Relapsed Neuroblastoma. Biol Blood Marrow Transplant. 2018 May;24(5):1005-1012. doi: 10.1016/j.bbmt.2017.12.805. Epub 2018 Jan 4.

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