Unrelated cord blood transplantation in patients with acquired refractory aplastic anemia: a nationwide phase II study

Regis Peffault de Latour, Sylvie Chevret, Charlotte Jubert, Anne Sirvent, Claire Galambrun, Annalisa Ruggeri, Virginie Gandemer, Jérôme Cornillon, Fanny Rialland, Jean-Hugues H. Dalle, Edouard Forcade, Benedicte Bruno, Catherine Paillard, Pierre S. Rorlich, Alexandra Salmon, Sabine Fürst, Flore Sicre de Fontbrune, Marie Therese Rubio, Jacques-Olivier Bay, Mohamad Mohty, Jerome Larghero, Eliane Gluckman and Gerard Socié

Key points

  • CB transplantation after FLU-CY-ATG-2-GyTBI with at least 4x107 frozen nucleated cells/kg leads to satisfactory OS in refractory SAA.

  • CB transplantation is a valuable curative option in young patients with refractory idiopathic SAA and no available matched unrelated donors.


Outcomes remain poor for patients with refractory severe aplastic anemia (SAA). Alternative donor transplantation may be considered, but results from previous studies have not been encouraging. We conducted a prospective nationwide phase II study to assess the efficacy and safety of unrelated cord blood transplantation (CBT) in patients with refractory SAA (APCORD protocol, NCT 01343953). To demonstrate a significant difference in one-year survival from 20% (null hypothesis) to 50% (alternative hypothesis), we needed to include 25 transplanted patients. Twenty-six patients (median age: 16 years) were therefore included. Eligibility criteria required one or two unrelated CB units, containing separately or together more than 4x107 frozen nucleated cells/kg recipient body weight. The conditioning regimen comprised fludarabine, cyclophosphamide, thymoglobulin and 2-Gy total body irradiation. With a median follow-up of 38.8 months, engraftment occurred in 23 patients (88%); cumulative incidences of grade II-IV acute and chronic GvHD were 45.8% and 36%, respectively. Twenty-three patients were alive at one year, with an overall survival rate of 88.5%, differing significantly from the expected 20% (p<0.0001) (84% overall survival at 2 years). CBT with units containing at least 4x107 frozen nucleated cells/kg is therefore a valuable curative option for young adults with refractory SAA and no available matched unrelated donors.

  • Submitted January 25, 2018.
  • Accepted May 4, 2018.