Unrelated cord blood transplantation in patients with idiopathic refractory severe aplastic anemia

a nationwide phase 2 study

Francophone Society of Bone Marrow Transplantation and Cellular Therapy

Research output: Contribution to journalArticle

Abstract

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 www.clinicaltrials.gov as #NCT01343953.

Original languageEnglish
Pages (from-to)750-754
Number of pages5
JournalBlood
Volume132
Issue number7
DOIs
Publication statusPublished - Aug 16 2018
Externally publishedYes

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Aplastic Anemia
Fetal Blood
Transplantation
Unrelated Donors
Antilymphocyte Serum
Survival
Whole-Body Irradiation
Graft vs Host Disease
Cyclophosphamide
Young Adult
Survival Rate
Body Weight
Tissue Donors
Safety
Incidence

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Unrelated cord blood transplantation in patients with idiopathic refractory severe aplastic anemia : a nationwide phase 2 study. / Francophone Society of Bone Marrow Transplantation and Cellular Therapy.

In: Blood, Vol. 132, No. 7, 16.08.2018, p. 750-754.

Research output: Contribution to journalArticle

Francophone Society of Bone Marrow Transplantation and Cellular Therapy. / Unrelated cord blood transplantation in patients with idiopathic refractory severe aplastic anemia : a nationwide phase 2 study. In: Blood. 2018 ; Vol. 132, No. 7. pp. 750-754.
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title = "Unrelated cord blood transplantation in patients with idiopathic refractory severe aplastic anemia: a nationwide phase 2 study",
abstract = "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 www.clinicaltrials.gov as #NCT01343953.",
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T1 - Unrelated cord blood transplantation in patients with idiopathic refractory severe aplastic anemia

T2 - a nationwide phase 2 study

AU - Francophone Society of Bone Marrow Transplantation and Cellular Therapy

AU - Peffault de Latour, Regis

AU - Chevret, Sylvie

AU - Jubert, Charlotte

AU - Sirvent, Anne

AU - Galambrun, Claire

AU - Ruggeri, Annalisa

AU - Gandemer, Virginie

AU - Cornillon, Jérôme

AU - Rialland, Fanny

AU - Dalle, Jean-Hugues

AU - Forcade, Edouard

AU - Bruno, Benedicte

AU - Paillard, Catherine

AU - Rorlich, Pierre S

AU - Salmon, Alexandra

AU - Fürst, Sabine

AU - Sicre de Fontbrune, Flore

AU - Rubio, Marie Therese

AU - Bay, Jacques-Olivier

AU - Mohty, Mohamad

AU - Larghero, Jerome

AU - Gluckman, Eliane

AU - Socié, Gerard

N1 - © 2018 by The American Society of Hematology.

PY - 2018/8/16

Y1 - 2018/8/16

N2 - 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 www.clinicaltrials.gov as #NCT01343953.

AB - 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 www.clinicaltrials.gov as #NCT01343953.

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