Incorporation of high-dose (131) I-metaiodobenzylguanidine treatment into killer immunoglobulin-like receptor/HLA-ligand mismatched haploidentical stem cell transplantation for children with neuroblastoma who failed tandem autologous stem cell transplantation.
2017
Background
We performed a pilot study (NCT 00793351) to evaluate the effectiveness and feasibility of a strategy incorporating high-dose 131I-metaiodobenzylguanidine (HD-MIBG) treatment into killer immunoglobulin-like receptor (KIR)/HLA-ligand mismatched haploidentical stem cell transplantation (haplo-SCT) in improving the survival of children with neuroblastoma who failed previous tandem autologous SCT.
Procedure
If the patient remained progression free with salvage treatment, HD-MIBG treatment (18 mCi/kg) was given prior to reduced-intensity conditioning (cyclophosphamide + fludarabine + antithymocyte globulin). Grafts from KIR/HLA-ligand mismatched, preferably BX haplotype, haploidentical donors were transplanted to enhance the graft-versus-tumor (GVT) effect.
Results
A total of seven patients were enrolled and three donors had a BX haplotype. Toxicities during HD-MIBG treatment and reduced-intensity conditioning were mild. Neutrophil recovery and complete or near complete donor chimerism were rapidly achieved. Six patients experienced acute graft-versus-host disease (GVHD; grade I in five and grade III in one), and four of six evaluable patients experienced chronic GVHD (two mild and two severe). Four patients died from tumor progression, one died from sepsis without progression, and the other two remained alive in complete response during 34 and 48 months posttransplant. All three patients remained progression free after BX haplotype SCT, whereas the other four experienced progression after AA haplotype SCT.
Conclusions
Our results suggest that the incorporation of HD-MIBG treatment in haplo-SCT and the use of BX haplotype donors might improve outcome, but this approach is currently limited by unacceptable GVHD. Further work focused on enhancement of GVT effects in relapsed neuroblastoma should be coupled with efforts to reduce GVHD.
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