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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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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