Abstract 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 131 IMIBG 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.
Castelli et al. (Fri,) studied this question.