Impact of donor-specific anti-HLA antibodies on graft failure and survival after reduced intensity conditioning-unrelated cord blood transplantation: a Eurocord, Société Francophone d'Histocompatibilité et d'Immunogénétique (SFHI) and Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) analysis.

Annalisa Ruggeri (1) , Vanderson Rocha (1) , Emeline Masson (2) , Myriam Labopin (3) , Renato Cunha (1) , Lena Absi (4) , Ali Boudifa (5) , Brigitte Coeffic (6) , Anne Devys (7, 8) , Muriel de Matteis (6) , Valérie Dubois (9) , Daniel Hanau (10) , Françoise Hau (11) , Isabelle Jollet (12) , Dominique Masson (13) , Beatrice Pedron (14) , Pascale Perrier (15) , Christophe Picard (16, 17) , Annie Ramouneau-Pigot (18) , Fernanda Volt (1) , Dominique Charron (19) , Eliane Gluckman (20) , Pascale Loiseau (21)

1 UPD7 - Université Paris Diderot - Paris 7
2 Inserm CIC 1431 - Centre d'Investigation Clinique de Besançon
3 CHU Saint-Antoine [AP-HP]
4 EFS - Etablissement français du sang, Auvergne-Loire [Saint-Etienne]
5 CHU Pitié-Salpêtrière [AP-HP]
6 Laboratoire d'histocompatibilité et d'immunogénétique [Angers]
7 SIMPAF - SImulations and Modeling for PArticles and Fluids
8 LPP - Laboratoire Paul Painlevé - UMR 8524
9 HLA Department
10 Biologie des Cellules Dendritiques Humaines
11 EFS - Etablissement français du sang - Normandie
12 EFS - Etablissement français du sang [Poitiers]
13 EFS - Etablissement français du sang - Auvergne-Rhône-Alpes
14 AP-HP Hôpital universitaire Robert-Debré [Paris]
15 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
16 ADES - Anthropologie bio-culturelle, Droit, Ethique et Santé
17 EFS - Alpes-Méditerranée - Etablissement Français du Sang - Alpes-Méditerranée
18 CHRU Montpellier - Hôpital Saint Eloi
19 Hématologie -Immunologie -Cibles thérapeutiques
20 Clinical Research Unit
21 Immunogénétique humaine

Graft failure is a major complication after unrelated cord blood transplantation. Presence of HLA-antibodies before cord blood transplantation may impact graft failure. To analyze the effect of anti-HLA antibodies on unrelated cord blood transplantation outcomes, we analyzed 294 unrelated cord blood transplant recipients after reduced intensity conditioning regimen. The majority of the patients (82%) were transplanted for malignancies, 60% with double-unrelated cord blood transplant, 63% were HLA mismatched. Retrospectively, pre-unrelated cord blood transplant serum was tested for HLA-Ab using Luminex™ platform. Results were interpreted as mean fluorescence intensity (MFI) against donor-specific mismatch. Among 62 recipients (23%) who had anti-HLA antibodies before unrelated cord blood transplant, 14 patients had donor specific anti-HLA antibodies (DSA) (7 were donor-specific anti-HLA antibodies for single unrelated cord blood transplant and 7 for double unrelated cord blood transplant). Donor specific anti-HLA antibodies threshold ranged from 1620-17629 of mean fluorescence intensity (MFI). Cumulative incidence of Day-60 neutrophil engraftment was 76%: 44% for recipients with donor specific anti-HLA antibodies and 81% in those without donor specific anti-HLA antibodies (P=0.006). The cumulative incidence of 1-year transplant related mortality was 46% in patients with donor specific anti-HLA antibodies and 32% in those without antibodies (P=0.06). The presence of donor specific anti-HLA antibodies was associated with a trend for decreased survival rate (42% vs. 29%; P=0.07). Donor specific anti-HLA antibody in recipients of unrelated cord blood transplant is associated with graft failure and decreased survival. Patient's screening for donor specific anti-HLA antibodies before unrelated cord blood transplantation is recommended before choosing an HLA mismatched cord blood unit. Whenever possible it is important to avoid selecting a unit for which the patient has donor specific anti-HLA antibodies.

Domaines: Sciences du Vivant [q-bio]; Immunologie

Annalisa Ruggeri, Vanderson Rocha, Emeline Masson, Myriam Labopin, Renato Cunha, et al.. Impact of donor-specific anti-HLA antibodies on graft failure and survival after reduced intensity conditioning-unrelated cord blood transplantation: a Eurocord, Société Francophone d'Histocompatibilité et d'Immunogénétique (SFHI) and Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) analysis.. Haematologica, 2013, 98 (7), pp.1154-60. ⟨10.3324/haematol.2012.077685⟩. ⟨hal-00870805⟩