Results of haploidentical transplant in patients with donor-specific antibodies : a survey on behalf of the Spanish Group of Hematopoietic Transplant and Cell Therapy
Bailén, Rebeca (Hospital General Universitario Gregorio Marañón)
Alenda, Raquel (Centro de Transfusión de la Comunidad de Madrid)
Herruzo-Delgado, Beatriz (Hospital Regional Universitario de Málaga)
Acosta-Fleitas, Cynthia (Hospital Universitario de Gran Canaria Dr. Negrín)
Vallés, Ana (Hospital Universitario Ramón y Cajal (Madrid))
Esquirol, Albert (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Fonseca, Marta (Hospital Clínico Universitario (Salamanca))
Solán, Laura (Hospital Universitario Fundación Jiménez Díaz)
Sánchez-Vadillo, Irene (Hospital Universitario La Paz (Madrid))
Bautista, Guiomar (Hospital Universitario Puerta de Hierro Majadahonda (Madrid))
Bento, Leyre (Hospital Universitari Son Espases (Palma de Mallorca, Balears))
López-Godino, Oriana (Hospital General Universitario Morales Meseguer (Múrcia))
Pérez-Martínez, Ariadna (Hospital Clínic Universitari (València))
Torrent Catarineu, Anna (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Zanabili, Joud (Hospital Universitario Central de Asturias)
Calbacho, Maria (Hospital Universitario 12 de Octubre (Madrid))
Moreno, Miguel Ángel (Centro de Transfusión de la Comunidad de Madrid)
Pascual-Cascón, María Jesús (Hospital Regional Universitario de Málaga)
Guerra-Domínguez, Luisa (Hospital Universitario de Gran Canaria Dr. Negrín)
Chinea, Anabelle (Hospital Universitario Ramón y Cajal (Madrid))
Garcia Cadenas, Irene (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
López-Corral, Lucía (Hospital Clínico Universitario (Salamanca))
Boix, Francisco (Universidad de Salamanca)
López Lorenzo, José Luis (Hospital Universitario Fundación Jiménez Díaz)
Humala, Karem (Hospital Universitario La Paz (Madrid))
Duarte, Rafael (Hospital Universitario Puerta de Hierro Majadahonda (Madrid))
Sampol, Antonia (Hospital Universitari Son Espases (Palma de Mallorca, Balears))
Heras, Inmaculada (Hospital General Universitario Morales Meseguer (Múrcia))
Vicario, José Luis (Centro de Transfusión de la Comunidad de Madrid)
Balas, Antonio (Centro de Transfusión de la Comunidad de Madrid)
Oarbeascoa, Gillen (Hospital General Universitario Gregorio Marañón)
Fernández-Caldas, Paula (Hospital General Universitario Gregorio Marañón)
Anguita, Javier (Universidad Complutense de Madrid)
Kwon, Mi (Universidad Complutense de Madrid)
Universitat Autònoma de Barcelona

Date:	2023
Abstract:	Donor-specific antibodies (DSAs) are IgG allo-antibodies against mismatched donor HLA molecules and can cause graft failure (GF) in the setting of haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Our aim was to report the experience of the Spanish Group of Hematopoietic Transplant (GETH-TC) in DSA-positive patients who had undergone haplo-HSCT. We conducted a survey of patients who underwent haplo-HSCT in GETH-TC centers between 2012 and 2021. Data were collected on the DSA assay used, monitoring strategy, complement fixation, criteria for desensitization, desensitization strategies and transplant outcomes. Fifteen centers from the GETH-TC responded to the survey. During the study period, 1,454 patients underwent haplo-HSCT. Seventy of the transplants were performed in 69 DSA-positive patients, all of whom lacked a suitable alternative donor; 61 (88%) patients were female (90% with prior pregnancies). All patients received post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis. Regarding baseline DSA intensity, 46 (67%) patients presented mean fluorescence intensity (MFI) >5,000, including 21 (30%) with MFI >10,000 and three (4%) with MFI >20,000. Six patients did not receive desensitization treatment, four of them with MFI <5,000. Of 63 patients receiving desensitization treatment, 48 (76%) were tested after desensitization therapy, and a reduction in intensity was confirmed in 45 (71%). Three patients (5%) experienced an increase in MFI after desensitization, two of whom experienced primary GF. Cumulative incidence of neutrophil engraftment at day 28 was 74% in a median of 18 days (IQR, 15─20); six patients died before engraftment due to toxicity or infection and eight patients had primary GF despite desensitization in seven of them. After a median follow-up of 30 months, two-year overall and event-free survival were 46. 5% and 39%, respectively. The two-year cumulative incidence of relapse was 16% and non-relapse mortality (NRM) was 43%. Infection was the most frequent cause of NRM, followed by endothelial toxicity. Multivariate analysis identified baseline MFI >20,000 as an independent risk factor for survival and an increase in titers after infusion as an independent risk factor for GF. Haplo-HSCT is feasible in DSA-positive patients, with high rates of engraftment after desensitization guided by DSA intensity. Baseline MFI >20,000 and increased intensity after infusion are risk factors for survival and GF.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	DSA kinetics ; Desensitization strategies ; Donor-specific antibodies ; Graft failure ; Haplo-hsct
Published in:	Frontiers in immunology, Vol. 14 (may 2023) , ISSN 1664-3224

DOI: 10.3389/fimmu.2023.1165759
PMID: 37304258

13 p, 3.3 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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Articles > Published articles