Results of haploidentical transplant in patients with donor-specific antibodies: a survey on behalf of the Spanish Group of Hematopoietic Transplant and Cell Therapy

• Published in: Frontiers in immunology Vol. 14; p. 1165759
• Main Authors: Bailén, Rebeca, Alenda, Raquel, Herruzo-Delgado, Beatriz, Acosta-Fleitas, Cynthia, Vallés, Ana, Esquirol, Albert, Fonseca, Marta, Solán, Laura, Sánchez-Vadillo, Irene, Bautista, Guiomar, Bento, Leyre, López-Godino, Oriana, Pérez-Martínez, Ariadna, Torrent, Anna, Zanabili, Joud, Calbacho, María, Moreno, Miguel Ángel, Pascual-Cascón, María Jesús, Guerra-Domínguez, Luisa, Chinea, Anabelle, García-Cadenas, Irene, López-Corral, Lucía, Boix-Giner, Francisco, López Lorenzo, José Luis, Humala, Karem, Duarte, Rafael, Sampol, Antonia, Heras, Inmaculada, Vicario, José Luis, Balas, Antonio, Oarbeascoa, Gillen, Fernández-Caldas, Paula, Anguita, Javier, Kwon, Mi
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 26.05.2023
• Subjects: Cell- and Tissue-Based Therapy; desensitization strategies; donor-specific antibodies; DSA kinetics; Female; graft failure; haplo-HSCT; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Immunoglobulin G; Immunology; Male; Pregnancy; Tissue Donors; Transplantation, Haploidentical; DSA kinetics; haplo-HSCT; desensitization strategies; donor-specific antibodies; graft failure
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2023.1165759

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.