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PLASTIC RECONSTRUCTIVE AND REGENERATIVE SURGERY

Original article

Ahead-of-Print

Donor-specific anti-HLA antibodies (DSAs) in patients undergoing allogeneic hematopoietic stem cell transplantation from mismatched donors on behalf of GITMO and AIBT

Authors

Ursula La Rocca , Roberto Ricci , Alfonso Piciocchi , Walter Barberi , Elena Oldani , Alida Dominietto , Raffaella Cerretti , Alessandra Picardi , Francesca Bonifazi , Riccardo Saccardi , Maura Faraci , Giovanni Grillo , Lucia Farina , Benedetto Bruno , Anna Grassi , Anna Proia , Elena Tagliaferri , Giuseppina De Simone , Michele Malagola , Michela Cerno , Simone Cesaro , Paolo Bernasconi , Lucia Prezioso , Paola Carluccio , Nicola Mordini , Matteo Pelosini , Attilio Olivieri , Patrizia Chiusolo , Stella Santarone , Michele Cimminiello , Roberto Crocchiolo , Franco Papola , Gianni Rombolà , Nicoletta Sacchi , Valeria Miotti , Lia Mele , Benedetta Mazzi , Fabio Ciceri , Massimo Martino , Anna Paola Iori

Key words: allogeneic stem cell transplantation, alloimmunization, anti-HLA antibodies, engraftment
DOI: 10.2450/BloodTransfus.790
Hematopoietic stem cell transplantation and cord blood banking
Publication Date: 2025-01-28

Abstract

Background - Antibodies directed against donor-specific HLA allele(s)/antigen(s)(DSAs) represent a known risk factor for hematopoietic stem cell transplantation (HSCT) engraftment. Still, the overall management needs to be standardized.

Material and methods - GITMO and AIBT ran a survey on DSAs in Italian Transplant Programs including mismatched HSCT performed between January 2014 and June 2017.

Results - One-thousand-thirty-three patients were proposed for the study, 804 were evaluable. Overall, 355 (44%) were screened: 91/355 (25.6%) showed anti-HLA antibodies, 23 DSAs (6.5%). Female gender and at least 4 previous pregnancies showed an impact on alloimmunization. Eleven patients with DSAs underwent desensitization. In seven cases no desensitization was employed. An alternative donor was selected for five patients. Neutrophil and platelet engraftment were obtained in 93.6% and 86.6% of the whole population, respectively, and were statistically associated with the absence of anti-HLA antibodies, ABO match, a higher number of infused nucleated cells and lack of a-GvHD. In addition, significant factors for platelet engraftment were the use of leuco-depleted transfusions, HLA match, younger age of the patient. Graft failure (GF) was associated with bone marrow stem cell source, and a lower number of infused CD34+. The detection of antibodies directed against both HLA classes, donor and patient age, the hematologic and molecular remission at HSCT, HLA match, ANC and PLTS engraftment, full donor engraftment within 28 days after HSCT, early and late GF, grade>II a-GVHD showed an impact on OS.

Discussion - Anti-HLA antibodies and DSAs were confirmed as risk factors affecting OS. DSAs were managed with various approaches resulting in stable engraftment in 81.9% of patients. Our study supports the clinical relevance of DSAs detection and management in mmHSCT. A standardized approach of DS is warranted.

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Authors

Ursula La Rocca - Hematology, Department of Translational and Precision Medicine, Sapienza, Rome, Italy; National Blood Center, Italian National Institute of Health, Rome, Italy

Roberto Ricci - Hematology, Department of Translational and Precision Medicine, Sapienza, Rome, Italy

Alfonso Piciocchi - GIMEMA Data Center, Rome, Italy

Walter Barberi - Hematology, Department of Translational and Precision Medicine, Sapienza, Rome, Italy

Elena Oldani - Bone Marrow Transplant Unit, ASST Papa Giovanni XXIII, Bergamo, Italy

Alida Dominietto - IRCCS Ospedale Policlinico S.Martino, Genoa, Italy

Raffaella Cerretti - Stem Cell Transplant Unit, Policlinico Tor Vergata, Rome, Italy

Alessandra Picardi - Stem Cell Transplant Unit, Policlinico Tor Vergata, Rome, Italy; Stem Cell Transplant Program of AORN Cardarelli, Naples, Italy

Francesca Bonifazi - IRCSS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

Riccardo Saccardi - Cell Therapy and Transfusion Medicine Department, Careggi University Hospital, Florence, Italy

Maura Faraci - Hematopoietic Stem Cell Transplantation Unit, IRCSS Istituto Giannina Gaslini, Genoa, Italy

Giovanni Grillo - ASST Great Metropolitan Hospital Niguarda, Milan, Italy

Lucia Farina - Foundation IRCCS-Italian National Cancer Institute, Milan, Italy

Benedetto Bruno - Division of Hematology and Stem Cell Therapy Unit, University of Turin, Turin, Italy

Anna Grassi - Bone Marrow Transplant Unit, ASST Papa Giovanni XXIII, Bergamo, Italy

Anna Proia - Unity of Hematology and Stem Cell Transplant, Azienda Ospedaliera S. Camillo Forlanini, Rome, Italy

Elena Tagliaferri - Hematology and BMT Unit, Foundation IRCCS Ca’Granda Ospedale Maggiore Policlinico, Milan, Italy

Giuseppina De Simone - Unità Operativa Complessa di Trapianto di Cellule Staminali Emopoietiche e Terapie Cellulari, Azienda Ospedaliera di Rilievo Nazionale Santobono-Pausilipon, Naples, Italy

Michele Malagola - Unit of Blood Diseases and Stem Cell Transplantation, ASST-Spedali Civili di Brescia, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy

Michela Cerno - Division of Hematology and Stem Cell Transplantation, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy

Simone Cesaro - Pediatric Hematology Oncology, Department of Mother and Child, Azienda Ospedaliera Universitaria Integrata, Verona, Italy

Paolo Bernasconi - Division of Hematology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy

Lucia Prezioso - Hematology and Stem Cell Transplant Unit, Ospedale Maggiore, Parma, Italy

Paola Carluccio - Unit of Hematology and Stem Cell Transplantation, AOUC Policlinico, Bari, Italy

Nicola Mordini - Hematology Division, Azienda Ospedaliera S. Croce e Carle, Cuneo, Italy

Matteo Pelosini - Clinical and Experimental Medicine, Section of Hematology, University of Pisa, Pisa, Italy

Attilio Olivieri - Hematology Department, University of Ancona, Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, Ancona, Italy

Patrizia Chiusolo - Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico A. Gemelli IRCCS, Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, Rome, Italy

Stella Santarone - Bone Marrow Transplant Center, Department of Oncology Hematology, Ospedale Civile, Pescara, Italy

Michele Cimminiello - Hematology and Bone Marrow Transplantation Unit, S. Carlo Hospital, Potenza, Italy

Roberto Crocchiolo - ASST Grande Ospedale Metropolitano Niguarda, Hematology Department, Milan, Italy

Franco Papola - Regional Centre of Immunohematology and Tissue Typing, S.Salvatore Hospital, L'Aquila, Italy,

Gianni Rombolà - Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy

Nicoletta Sacchi - Italian Bone Marrow Donor Registry, E. O. Ospedali Galliera, Genoa, Italy

Valeria Miotti - Laboratory of Immunogenetics, Santa Maria della Misericordia University Hospital, Udine, Italy; Italian Society for Immunogenetics and Transplantation Biology (AIBT), Bologna, Italy

Lia Mele - HLA Laboratory and stem cell processing, A.O. SS Antonio e Biagio e C. Arrigo, Alessandria, Italy; Italian Society for Immunogenetics and Transplantation Biology (AIBT), Bologna, Italy

Benedetta Mazzi - Immunogenetics Laboratory, Immuno-Hematology and Transfusion Medicine Unit, San Raffaele Scientific Institute, Milan, Italy

Fabio Ciceri - University Vita-Salute San Raffaele, IRCCS, S. Raffaele Scientific Institute, Milan, Italy

Massimo Martino - Stem Cell Transplant and Cellular Therapies Unit, Hemato-Oncology and Radiotherapy Department, "Bianchi-Melacrino-Morelli" Hospital, Reggio Calabria, Italy

Anna Paola Iori - Hematology, Department of Translational and Precision Medicine, Sapienza, Rome, Italy

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