Poster Presentation Advances in Neuroblastoma Research Congress 2016

Significantly reduced relapse rate after KIR ligand incompatible allogeneic cord blood transplantation with nonmyeloablative conditioning for primary stage IV neuroblastoma (#227)

Yoshiyuki Takahashi 1 , Atsushi Narita 1 , Shinsuke Kataoka 1 , Nobuhiro Nishio 1 , Yinyan Xu 1 , Yusuke Okuno 1 , Daiei Kojima 1 , Kyogo Suzuki 1 , Norihiro Murakami 1 , Rieko Taniguchi 1 , Daisuke Ichikawa 1 , Motoharu Hamada 1 , Yuko Sekiya 1 , Nozomu Kawashima 1 , Eri Nishikawa 1 , Michi Kamei 1 , Hirotoshi Sakaguchi 2 , Nao Yoshida 2 , Hideki Muramatsu 1 , Asahito Hama 1 , Keizo Horibe 3 , Koji Kato 2 , Seiji Kojima 1
  1. Nagoya University Graduate School of Medicine, Nagoya, AICHI, Japan
  2. Department of Hematology and Oncology, Children’s Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya, Aichi, Japan
  3. Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Aichi, Japan

Background: We initiated prospective clinical trial of allogeneic cord blood transplantation (CBT) from Killer immunoglobulin-like receptor (KIR) ligand incompatible donor for stage IV neuroblastoma patients in 2008. Methods: Eligibility criteria of this study was newly diagnosed stage IV neuroblastoma patients with one of the following three criteria 1)Chemo-resistant disease 2)10 years or older at diagnosis 3)MYCN amplification. We scheduled CBT with reduced intensity conditioning regimen about three months after high-dose chemotherapy followed by autologous PBSCT. Single inhibitory KIR expressed NK cells with no corresponding recipient’s HLA were monitored by flowcytometry before and after CBT to assess the expansion of alloreactive NK cells in vivo. We also retrospectively analyzed the outcome of 82 patients with high risk neuroblastoma treated without KIR ligand incompatible CBT in Nagoya University Hospital between 1982 and 2014 as a control cohort. Results: Twenty consecutive patients who matched eligibility criteria underwent KIR ligand incompatible CBT (11 chemo-resistant, 7 MYCN amplification and 2 older age). The median age was 4 (range: 1-10) years old at diagnosis, consisting of 8 boys and 12 girls. No patients developed grade III or more acute GVHD and chronic GVHD. Two patients died in this group because of BU related lung toxicity and only one patient relapsed 7 months after CBT. Significantly reduced cumulative incidence of relapse (7.1%) with the median follow-up period of 52 (5-84) months was observed compared with 51.0% in control cohort. 3-year progression free survival in KIR ligand incompatible CBT group was significantly better than others (83.4% vs 40.7%, p=0.042). Single inhibitory KIR expressed NK cells significantly expanded after CBT (p=0.0007). Finally, multivariate analysis revealed only KIR ligand incompatibility was significantly better covariate factor for relapse. Conclusions: CBT from KIR ligand incompatible donor significantly reduced the relapse rate with regard to better progression free survival in stage IV neuroblastoma.