Posttransplant cyclophosphamide as GVHD prophylaxis in patients receiving mismatched unrelated HCT: the PHYLOS trial
Abstract: Posttransplant high-dose cyclophosphamide (PTCy) is effective in overcoming the negative impact of HLA disparity in the haploidentical setting. In light of these results, we investigated the efficacy of PTCy, in improving clinical outcomes of hematopoietic stem cell transplantation (HSCT)...
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Elsevier
2025-04-01
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| Series: | Blood Advances |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2473952925000941 |
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| author | Anna Maria Raiola Benedetto Bruno Antonio Maria Risitano Federico Mosna Irene Maria Cavattoni Francesco Onida Giorgia Saporiti Francesca Patriarca Marta Lisa Battista Vincenzo Pavone Anna Mele Patrizia Chiusolo Simona Sica Barbara Loteta Carmen di Grazia Angelo Michele Carella Dalila Salvatore Enrico Morello Alessandro Leoni Luisa Giaccone Paolo Bernasconi Elisabetta Terruzzi Nicola Mordini Carlo Borghero Francesco Zallio Mario Luppi Anna Grassi Attilio Olivieri Eugenia Piras Nicoletta Sacchi Giovannino Ciccone Anna Castiglione Eliana Degrandi Emanuele Angelucci Massimo Martino Francesca Bonifazi |
| author_facet | Anna Maria Raiola Benedetto Bruno Antonio Maria Risitano Federico Mosna Irene Maria Cavattoni Francesco Onida Giorgia Saporiti Francesca Patriarca Marta Lisa Battista Vincenzo Pavone Anna Mele Patrizia Chiusolo Simona Sica Barbara Loteta Carmen di Grazia Angelo Michele Carella Dalila Salvatore Enrico Morello Alessandro Leoni Luisa Giaccone Paolo Bernasconi Elisabetta Terruzzi Nicola Mordini Carlo Borghero Francesco Zallio Mario Luppi Anna Grassi Attilio Olivieri Eugenia Piras Nicoletta Sacchi Giovannino Ciccone Anna Castiglione Eliana Degrandi Emanuele Angelucci Massimo Martino Francesca Bonifazi |
| author_sort | Anna Maria Raiola |
| collection | DOAJ |
| description | Abstract: Posttransplant high-dose cyclophosphamide (PTCy) is effective in overcoming the negative impact of HLA disparity in the haploidentical setting. In light of these results, we investigated the efficacy of PTCy, in improving clinical outcomes of hematopoietic stem cell transplantation (HSCT) from a mismatched unrelated donor (MMUD) in patients with acute myeloid malignancies by reducing the incidence and severity of acute graft-versus-host disease (aGVHD). A prospective, single-arm, phase 2 study (PHYLOS) was conducted by the Gruppo Italiano Trapianto di Midollo Osseo. The ethical committees of the participating centers approved the study (EURODRACT 2017-003530-85). A total of 77 consecutive patients (acute myeloid leukemia: 64; myelodysplastic syndrome: 13) were enrolled at 26 Italian transplant centers (January 2020-November 2022). Median age of the patients was 53 (range, 19-65) years. The 100-day cumulative incidence of grades 2 to 4 aGVHD was 18.2% (95% CI, 10.6-27.6) and of grades 3 to 4 was 6.5% (95% CI, 3.1-15.1). Seventy-one patients (92%) had full-donor chimerism with complete neutrophil engraftment by day +30. One-year cumulative incidence of chronic GVHD was 13.4% (95% CI, 6.9-22.1). One-year cumulative incidence of nonrelapse mortality was 9.1% (95% CI, 4.0-16.9), and the relapse rate was 23.8% (95% CI, 14.9-33.9). One-year overall survival and graft relapse-free survival were 78.6% (95% CI, 67.4-86.3) and 55.3% (95% CI, 43.4-65.7), respectively. Our study in a homogeneous patient cohort suggests that PTCy leads to a low rate of aGVHD and improves clinical outcomes of HSCT from MMUD. This trial was registered at www.clinicaltrials.gov as #NCT03270748. |
| format | Article |
| id | doaj-art-ff9540074cab476d90f164ebe2e26575 |
| institution | DOAJ |
| issn | 2473-9529 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Advances |
| spelling | doaj-art-ff9540074cab476d90f164ebe2e265752025-08-20T03:10:24ZengElsevierBlood Advances2473-95292025-04-01981966197510.1182/bloodadvances.2024015173Posttransplant cyclophosphamide as GVHD prophylaxis in patients receiving mismatched unrelated HCT: the PHYLOS trialAnna Maria Raiola0Benedetto Bruno1Antonio Maria Risitano2Federico Mosna3Irene Maria Cavattoni4Francesco Onida5Giorgia Saporiti6Francesca Patriarca7Marta Lisa Battista8Vincenzo Pavone9Anna Mele10Patrizia Chiusolo11Simona Sica12Barbara Loteta13Carmen di Grazia14Angelo Michele Carella15Dalila Salvatore16Enrico Morello17Alessandro Leoni18Luisa Giaccone19Paolo Bernasconi20Elisabetta Terruzzi21Nicola Mordini22Carlo Borghero23Francesco Zallio24Mario Luppi25Anna Grassi26Attilio Olivieri27Eugenia Piras28Nicoletta Sacchi29Giovannino Ciccone30Anna Castiglione31Eliana Degrandi32Emanuele Angelucci33Massimo Martino34Francesca Bonifazi35Department of Hematology and Cellular Therapy, Istituo di Ricovero E Cura A Carattere Scientifico, Ospedale Policlinico San Martino, Genoa, Italy; Correspondence: Anna Maria Raiola, Istituo di Ricovero E Cura A Carattere Scientifico Ospedale Policlinico San Martino, Largo R Benzi 10, 16132 Genoa, Italy;Division of Hematology, Azienda Ospedaliera Universitaria Citta' della Salute e della Scienza di Torino, and Department of Biotechnologies and Health Sciences, University of Torino, Turin, ItalyHematology and Bone Marrow Transplant Unit, Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino, Avellino, ItalyHematology and Bone Marrow Transplantation Unit, Hospital of Bolzano (SABES-Azienda Sanitaria dell'Alto Adige), Teaching Hospital of Paracelsus Medical University, Bolzano, ItalyHematology and Bone Marrow Transplantation Unit, Hospital of Bolzano (SABES-Azienda Sanitaria dell'Alto Adige), Teaching Hospital of Paracelsus Medical University, Bolzano, ItalyHematology and Bone Marrow Transplantation Unit, Azienda Socio Sanitaria Territoriale Fatebenefratelli-Sacco, University of Milan, Milan, Italy; Centro Trapianti Midollo Osseo e Terapie Cellulari-Struttura Complessa Ematologia, Fondazione Istituo di Ricovero E Cura A Carattere Scientifico, Ca' Granda Ospedale Maggiore Policlinico, Milan, ItalyCentro Trapianti Midollo Osseo e Terapie Cellulari-Struttura Complessa Ematologia, Fondazione Istituo di Ricovero E Cura A Carattere Scientifico, Ca' Granda Ospedale Maggiore Policlinico, Milan, ItalyDivision of Hematology, S. Maria della Misericordia Hospital, Dipartimento di Medicina, Università di Udine, Azienda Sanitaria Universitaria Friuli Centrale, Udine, ItalyDivision of Hematology, S. Maria della Misericordia Hospital, Dipartimento di Medicina, Università di Udine, Azienda Sanitaria Universitaria Friuli Centrale, Udine, ItalyUnità Operativa Complessa Ematologia con Trapianto, Azienda Ospedale Car Panico Tricase (Lecce), Tricase, ItalyUnità Operativa Complessa Ematologia con Trapianto, Azienda Ospedale Car Panico Tricase (Lecce), Tricase, ItalySezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, Rome, Italy; Dipartimento di Scienze di laboratorio ed Ematologiche, Fondazione Policlinico A. Gemelli Istituo di Ricovero E Cura A Carattere Scientifico, Rome, ItalySezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, Rome, Italy; Dipartimento di Scienze di laboratorio ed Ematologiche, Fondazione Policlinico A. Gemelli Istituo di Ricovero E Cura A Carattere Scientifico, Rome, ItalyStem Cell Transplantation and Cellular Therapies Unit, Grande Ospedale Metropolitano, “Bianchi-Melacrino-Morelli,” Reggio Calabria, ItalyDepartment of Hematology and Cellular Therapy, Istituo di Ricovero E Cura A Carattere Scientifico, Ospedale Policlinico San Martino, Genoa, ItalyDepartment of Hematology and Stem Cell Transplant Unit, Fondazione Istituo di Ricovero E Cura A Carattere Scientifico Casa Sollievo della Sofferenza, Foggia, ItalyDepartment of Hematology and Stem Cell Transplant Unit, Fondazione Istituo di Ricovero E Cura A Carattere Scientifico Casa Sollievo della Sofferenza, Foggia, ItalyBlood Diseases and Cell Therapies Unit, Bone Marrow Transplant Unit, “Azienda Socio Sanitaria Territoriale-Spedali Civili” Hospital of Brescia, Brescia, Italy; Department of Clinical and Experimental Sciences, University of Brescia, Brescia, ItalyBlood Diseases and Cell Therapies Unit, Bone Marrow Transplant Unit, “Azienda Socio Sanitaria Territoriale-Spedali Civili” Hospital of Brescia, Brescia, Italy; Department of Clinical and Experimental Sciences, University of Brescia, Brescia, ItalyDivision of Hematology, Azienda Ospedaliera Universitaria Citta' della Salute e della Scienza di Torino, and Department of Biotechnologies and Health Sciences, University of Torino, Turin, ItalyHematopoietic Stem Cell Unit, Hematology Department, Fondazione Istituo di Ricovero E Cura A Carattere Scientifico Policlinico San Matteo, Pavia, ItalyHaematology Unit, Istituo di Ricovero E Cura A Carattere Scientifico San Gerardo, Monza, ItalyDivision of Hematology, Azienda Ospedaliera S. Croce e Carle, Cuneo, ItalyHematology Department, “San Bortolo” Hospital, Vicenza, ItalyHematology Department, SS Antonio and Biagio and C. Arrigo Hospital, Alessandria, ItalyEmatologia, Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto, Università degli Studi di Modena e Reggio Emilia, Modena, ItalyHematology-Bone Marrow Transplantation Unit Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, ItalyClinica di Ematologia, Azienda Ospedaliero Universitaria delle Marche, Ancona, ItalyHematology Unit, Businco Hospital, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyItalian Bone Marrow Donor Registry, E.O. Galliera Hospitals, Genoa, ItalyUnit of Clinical Epidemiology, Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino e Centro Prevenzione Oncologica Piemonte, Turin, ItalyUnit of Clinical Epidemiology, Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino e Centro Prevenzione Oncologica Piemonte, Turin, ItalyTrial Office Gruppo Italiano per il Trapianto di Midollo Osseo, cellule staminali emopoietiche e terapia Cellulare, Bologna, ItalyDepartment of Hematology and Cellular Therapy, Istituo di Ricovero E Cura A Carattere Scientifico, Ospedale Policlinico San Martino, Genoa, ItalyStem Cell Transplantation and Cellular Therapies Unit, Grande Ospedale Metropolitano, “Bianchi-Melacrino-Morelli,” Reggio Calabria, ItalyIstituo di Ricovero E Cura A Carattere Scientifico Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyAbstract: Posttransplant high-dose cyclophosphamide (PTCy) is effective in overcoming the negative impact of HLA disparity in the haploidentical setting. In light of these results, we investigated the efficacy of PTCy, in improving clinical outcomes of hematopoietic stem cell transplantation (HSCT) from a mismatched unrelated donor (MMUD) in patients with acute myeloid malignancies by reducing the incidence and severity of acute graft-versus-host disease (aGVHD). A prospective, single-arm, phase 2 study (PHYLOS) was conducted by the Gruppo Italiano Trapianto di Midollo Osseo. The ethical committees of the participating centers approved the study (EURODRACT 2017-003530-85). A total of 77 consecutive patients (acute myeloid leukemia: 64; myelodysplastic syndrome: 13) were enrolled at 26 Italian transplant centers (January 2020-November 2022). Median age of the patients was 53 (range, 19-65) years. The 100-day cumulative incidence of grades 2 to 4 aGVHD was 18.2% (95% CI, 10.6-27.6) and of grades 3 to 4 was 6.5% (95% CI, 3.1-15.1). Seventy-one patients (92%) had full-donor chimerism with complete neutrophil engraftment by day +30. One-year cumulative incidence of chronic GVHD was 13.4% (95% CI, 6.9-22.1). One-year cumulative incidence of nonrelapse mortality was 9.1% (95% CI, 4.0-16.9), and the relapse rate was 23.8% (95% CI, 14.9-33.9). One-year overall survival and graft relapse-free survival were 78.6% (95% CI, 67.4-86.3) and 55.3% (95% CI, 43.4-65.7), respectively. Our study in a homogeneous patient cohort suggests that PTCy leads to a low rate of aGVHD and improves clinical outcomes of HSCT from MMUD. This trial was registered at www.clinicaltrials.gov as #NCT03270748.http://www.sciencedirect.com/science/article/pii/S2473952925000941 |
| spellingShingle | Anna Maria Raiola Benedetto Bruno Antonio Maria Risitano Federico Mosna Irene Maria Cavattoni Francesco Onida Giorgia Saporiti Francesca Patriarca Marta Lisa Battista Vincenzo Pavone Anna Mele Patrizia Chiusolo Simona Sica Barbara Loteta Carmen di Grazia Angelo Michele Carella Dalila Salvatore Enrico Morello Alessandro Leoni Luisa Giaccone Paolo Bernasconi Elisabetta Terruzzi Nicola Mordini Carlo Borghero Francesco Zallio Mario Luppi Anna Grassi Attilio Olivieri Eugenia Piras Nicoletta Sacchi Giovannino Ciccone Anna Castiglione Eliana Degrandi Emanuele Angelucci Massimo Martino Francesca Bonifazi Posttransplant cyclophosphamide as GVHD prophylaxis in patients receiving mismatched unrelated HCT: the PHYLOS trial Blood Advances |
| title | Posttransplant cyclophosphamide as GVHD prophylaxis in patients receiving mismatched unrelated HCT: the PHYLOS trial |
| title_full | Posttransplant cyclophosphamide as GVHD prophylaxis in patients receiving mismatched unrelated HCT: the PHYLOS trial |
| title_fullStr | Posttransplant cyclophosphamide as GVHD prophylaxis in patients receiving mismatched unrelated HCT: the PHYLOS trial |
| title_full_unstemmed | Posttransplant cyclophosphamide as GVHD prophylaxis in patients receiving mismatched unrelated HCT: the PHYLOS trial |
| title_short | Posttransplant cyclophosphamide as GVHD prophylaxis in patients receiving mismatched unrelated HCT: the PHYLOS trial |
| title_sort | posttransplant cyclophosphamide as gvhd prophylaxis in patients receiving mismatched unrelated hct the phylos trial |
| url | http://www.sciencedirect.com/science/article/pii/S2473952925000941 |
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