Unrelated cord blood transplantation in patients with idiopathic refractory severe aplastic anemia: a nationwide phase 2 study

Regis Peffault de Latour, Sylvie Chevret, Charlotte Jubert, Anne Sirvent, Claire Galambrun, Annalisa Ruggeri, Virginie Gandemer, Jérôme Cornillon, Fanny Rialland, Jean-Hugues 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 on behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy

Key Points

  • CBT after FLU-CY-ATG-2-Gy TBI with at least 4 × 107 frozen NCs per kilogram leads to satisfactory OS in refractory SAA.

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


Outcomes remain poor for refractory severe aplastic anemia (SAA) patients. Alternative donor transplantation may be considered, but results from previous studies are not encouraging. We conducted a prospective nationwide phase 2 study to assess unrelated cord blood (CB) transplantation (CBT) efficacy and safety in refractory SAA patients (Aplastic Anemia and Cord Blood Transplantation protocol). To demonstrate a significant difference in 1-year survival from 20% (null hypothesis) to 50% (alternative hypothesis), we needed to include 25 transplanted patients and therefore included 26 (median age, 16 years). Eligibility criteria required 1 or 2 unrelated CB units, containing separately or together >4 × 107 frozen nucleated cells (NCs) per kilogram of recipient body weight. Conditioning regimen comprised fludarabine (FLU), cyclophosphamide (CY), antithymocyte globulin (ATG), and 2-Gy total body irradiation (TBI). With a median follow-up of 38.8 months, engraftment occurred in 23 patients (88%); cumulative incidences of grade II-IV acute and chronic graft-versus-host disease were 45.8% and 36%, respectively. Twenty-three patients were alive at 1 year, with an 88.5% overall survival (OS) rate, differing significantly from the expected 20% (P < .0001; 84% OS at 2 years). CBT with units containing ≥4 × 107 frozen NCs per kilogram is therefore a valuable curative option for young adults with refractory SAA and no available matched unrelated donors. This trial was registered at as #NCT01343953.

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