Haploidentical stem cell transplantation in newly diagnosed high-risk neuroblastoma: Results from a single-arm,...

With increasing data on graft-versus-tumor (GVT) effect in neuroblastoma, we aimed to evaluate the possibility of haploidentical stem cell transplantation (HSCT) as a technique to induce GVT and thereby improve outcomes in high-risk neuroblastoma.

We performed a prospective, single-arm study and included children from 18 months to 18 years of age diagnosed with high-risk neuroblastoma and who underwent a haploidentical HSCT from a parent donor. All children were started on induction chemotherapy as per the SIOP-Europa-Neuroblastoma (SIOPEN) protocol, followed by assessment and surgery when feasible. Conditioning in the unmanipulated graft included thiotepa/fludarabine/busulfan. With a T-depleted graft, conditioning included rabbit anti-thymocyte globulin/fludarabine/thiotepa/melphalan.

Of the five children, one child received T-depleted and four children received T-replete stem cells with posttransplant cyclophosphamide, with 100% engraftment, no regimen-related toxicities, and documented remission. Grade I/II skin GVHD occurred in all children who responded to steroids. We administered involved-field radiotherapy in four children around D + 60-75 post-HSCT, followed by 13-cis retinoic acid. At 1 year post-HSCT, three had isolated central nervous system relapse; one child had isolated pelvic bone relapse. One child relapsed 2 months post-HSCT. Progression-free survival was 12 months in 4/5 children and 6 months in one child. All except one child succumbed to progressive disease post relapse.

Children with high-risk neuroblastoma continued to relapse within a year post-HSCT in our cohort. Significant improvement in outcomes was not demonstrated with haploidentical HSCT. We urgently need new strategies including deeper remission induction with upfront metaiodobenzylguanidine (MIBG) therapy followed by HSCT to improve the outcomes.