Results of haploidentical transplant in patients with donor-specific antibodies: a survey on behalf of the Spanish Group of Hematopoietic Transplant and Cell Therapy
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 
Published: May 2023

Background

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.

Methods

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.

Results

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) &gt;5,000, including 21 (30%) with MFI &gt;10,000 and three (4%) with MFI &gt;20,000. Six patients did not receive desensitization treatment, four of them with MFI &lt;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 &gt;20,000 as an independent risk factor for survival and an increase in titers after infusion as an independent risk factor for GF.

Conclusions

Haplo-HSCT is feasible in DSA-positive patients, with high rates of engraftment after desensitization guided by DSA intensity. Baseline MFI &gt;20,000 and increased intensity after infusion are risk factors for survival and GF.