Scholarlink

<p>Very high-risk neuroblastoma is induction-refractory and often harbors mutations in RAS and/or p53 signaling combined with telomere maintenance mechanisms. Event-free survival is &lt;20% in these children. Patients unable to mobilize sufficient hematopoietic stem cells to harvest for busulfan/melphalan-based high-dose chemotherapy before autologous transplantation are also at high risk for relapse. Haploidentical stem cell transplantation (haplo-SCT), offering graft-versus-tumor effects and enhanced antibody-dependent cellular cytotoxicity, has emerged as a feasible treatment. We report administration of a conditioning regimen combining myeloablative busulfan/melphalan anti-tumor therapy with the immunological advantages of haplo-SCT and GD2-directed antibody-based immunotherapy with dinutuximab beta (DB). A 5-patient pilot cohort was treated with systemic induction (salvage) therapy and local therapy per national guidelines. Prior to busulfan, melphalan, fludarabine and antithymocyte globulin conditioning followed by T/B-cell-depleted haplo-SCT and 6 DB cycles, 2 patients received [<sup>131</sup>I]MIBG therapy. All patients were successfully engrafted. Three of five patients are alive and have remained in first complete remission for 7.3, 6.3 and 1.5 years after haplo-SCT, while two patients experienced events (one relapse, one non-relapse death). Primary busulfan-based haplo-SCT combined with DB immunotherapy was feasible and effective. Early results suggest a survival benefit for these pediatric patient subgroups at very high risk. Confirmation in a larger controlled trial is warranted.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

A pilot study combining primary busulfan-based haploidentical stem cell transplantation with GD2 antibody to treat high-risk neuroblastoma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月29日

查看全文
  • Sveva Castelli,
  • Tim Flaadt,
  • Franziska Schulze,
  • Theresa M. Thole-Kliesch,
  • Felix Zirngibl,
  • Lena Oevermann,
  • Annette Künkele,
  • Kathy Astrahantseff,
  • Stefanie Schulte,
  • Louisa Duell,
  • Joerg Fuchs,
  • Thorsten Simon,
  • Barbara Hero,
  • Patrick Hundsdoerfer,
  • Julian M. M. Rogasch,
  • Peter Lang,
  • Steven Warmann,
  • Arend von Stackelberg,
  • Johannes H. Schulte,
  • Angelika Eggert,
  • Hedwig E. Deubzer

摘要

Very high-risk neuroblastoma is induction-refractory and often harbors mutations in RAS and/or p53 signaling combined with telomere maintenance mechanisms. Event-free survival is <20% in these children. Patients unable to mobilize sufficient hematopoietic stem cells to harvest for busulfan/melphalan-based high-dose chemotherapy before autologous transplantation are also at high risk for relapse. Haploidentical stem cell transplantation (haplo-SCT), offering graft-versus-tumor effects and enhanced antibody-dependent cellular cytotoxicity, has emerged as a feasible treatment. We report administration of a conditioning regimen combining myeloablative busulfan/melphalan anti-tumor therapy with the immunological advantages of haplo-SCT and GD2-directed antibody-based immunotherapy with dinutuximab beta (DB). A 5-patient pilot cohort was treated with systemic induction (salvage) therapy and local therapy per national guidelines. Prior to busulfan, melphalan, fludarabine and antithymocyte globulin conditioning followed by T/B-cell-depleted haplo-SCT and 6 DB cycles, 2 patients received [131I]MIBG therapy. All patients were successfully engrafted. Three of five patients are alive and have remained in first complete remission for 7.3, 6.3 and 1.5 years after haplo-SCT, while two patients experienced events (one relapse, one non-relapse death). Primary busulfan-based haplo-SCT combined with DB immunotherapy was feasible and effective. Early results suggest a survival benefit for these pediatric patient subgroups at very high risk. Confirmation in a larger controlled trial is warranted.