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Haploidentical Stem Cell Transplantation for Refractory/Relapsed Neuroblastoma

Illhardt, Toni; Toporski, Jacek LU ; Feuchtinger, Tobias; Turkiewicz, Dominik; Teltschik, Heiko Manuel; Ebinger, Martin; Schwarze, Carl Philipp; Holzer, Ursula; Lode, Holger N. and Albert, Michael H., et al. (2018) In Biology of Blood and Marrow Transplantation
Abstract

Pediatric patients with refractory or relapsed metastatic neuroblastoma (NBL) have a poor prognosis despite autologous stem cell transplantation (SCT). Allogeneic SCT from a haploidentical donor has a remarkable alloreactive effect in patients with leukemia; thus, we evaluated this approach in children with very high-risk NBL. We analyzed data from 2 prospective phase I/II trials. A total of 26 patients with refractory (n = 5), metastatic relapsed (n = 20), or locally relapsed MYCN-positive (n = 1) NBL received a median of 17 × 106/kg T/B cell-depleted CD34+ stem cells with 68 × 103/kg residual T cells and 107 × 106/kg natural killer cells. The conditioning regimen comprised melphalan,... (More)

Pediatric patients with refractory or relapsed metastatic neuroblastoma (NBL) have a poor prognosis despite autologous stem cell transplantation (SCT). Allogeneic SCT from a haploidentical donor has a remarkable alloreactive effect in patients with leukemia; thus, we evaluated this approach in children with very high-risk NBL. We analyzed data from 2 prospective phase I/II trials. A total of 26 patients with refractory (n = 5), metastatic relapsed (n = 20), or locally relapsed MYCN-positive (n = 1) NBL received a median of 17 × 106/kg T/B cell-depleted CD34+ stem cells with 68 × 103/kg residual T cells and 107 × 106/kg natural killer cells. The conditioning regimen comprised melphalan, fludarabine, thiotepa, OKT3, and a short course of mycophenolate mofetil post-transplantation. Engraftment occurred in 96% of the patients. Event-free survival and overall survival at 5 years were 19% and 23%, respectively. No transplantation-related mortality was observed, and the single death was due to progression/subsequent relapse. The median duration of follow-up was 8.1 years. Patients in complete remission before SCT had a significantly better prognosis than those with residual tumor load (P < .01). All patients with progressive disease before SCT relapsed within 1 year. Grade II and grade III acute graft-versus-host disease (GVHD) occurred in 31% and 12% of the patients, respectively. Chronic limited and extensive GVHD occurred in 28% and 10%, respectively. Our data indicate that haploidentical SCT is a feasible treatment option that can induce long-term remission in some patients with NBL with tolerable side effects, and may enable the development of further post-transplantation therapeutic strategies based on the donor-derived immune system.

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@article{be609918-8ce9-4a77-8674-5a5ec7564065,
  abstract     = {<p>Pediatric patients with refractory or relapsed metastatic neuroblastoma (NBL) have a poor prognosis despite autologous stem cell transplantation (SCT). Allogeneic SCT from a haploidentical donor has a remarkable alloreactive effect in patients with leukemia; thus, we evaluated this approach in children with very high-risk NBL. We analyzed data from 2 prospective phase I/II trials. A total of 26 patients with refractory (n = 5), metastatic relapsed (n = 20), or locally relapsed MYCN-positive (n = 1) NBL received a median of 17 × 10<sup>6</sup>/kg T/B cell-depleted CD34<sup>+</sup> stem cells with 68 × 10<sup>3</sup>/kg residual T cells and 107 × 10<sup>6</sup>/kg natural killer cells. The conditioning regimen comprised melphalan, fludarabine, thiotepa, OKT3, and a short course of mycophenolate mofetil post-transplantation. Engraftment occurred in 96% of the patients. Event-free survival and overall survival at 5 years were 19% and 23%, respectively. No transplantation-related mortality was observed, and the single death was due to progression/subsequent relapse. The median duration of follow-up was 8.1 years. Patients in complete remission before SCT had a significantly better prognosis than those with residual tumor load (P &lt; .01). All patients with progressive disease before SCT relapsed within 1 year. Grade II and grade III acute graft-versus-host disease (GVHD) occurred in 31% and 12% of the patients, respectively. Chronic limited and extensive GVHD occurred in 28% and 10%, respectively. Our data indicate that haploidentical SCT is a feasible treatment option that can induce long-term remission in some patients with NBL with tolerable side effects, and may enable the development of further post-transplantation therapeutic strategies based on the donor-derived immune system.</p>},
  author       = {Illhardt, Toni and Toporski, Jacek and Feuchtinger, Tobias and Turkiewicz, Dominik and Teltschik, Heiko Manuel and Ebinger, Martin and Schwarze, Carl Philipp and Holzer, Ursula and Lode, Holger N. and Albert, Michael H. and Gruhn, Bernd and Urban, Christian and Dykes, Josefina H. and Teuffel, Oliver and Schumm, Michael and Handgretinger, Rupert and Lang, Peter},
  issn         = {1083-8791},
  keyword      = {Allogeneic stem cell transplantation,Graft-versus-host disease,Graft-versus-tumor effect,Haploidentical,Neuroblastoma,Transplantation-related mortality},
  language     = {eng},
  publisher    = {Elsevier},
  series       = {Biology of Blood and Marrow Transplantation},
  title        = {Haploidentical Stem Cell Transplantation for Refractory/Relapsed Neuroblastoma},
  url          = {http://dx.doi.org/10.1016/j.bbmt.2017.12.805},
  year         = {2018},
}