Post-transplant cyclophosphamide in haploidentical stem cell transplantation: evaluating the impact of transplant conditioning intensity

BackgroundThe introduction of posttransplant cyclophosphamide (PTCy) is one of the major achievements in the field of haploidentical stem cell transplantation (haplo-HCT). The transplant conditioning intensity (TCI) score is a refined classification of conditioning regimens that assigns weight score...

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Main Authors: Umberto Pizzano, Simona Piemontese, Gabriele Facchin, Raffaella Greco, Marta Lisa Battista, Jacopo Peccatori, Renato Fanin, Fabio Ciceri, Francesca Patriarca, Maria Teresa Lupo-Stanghellini
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Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1610391/full
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author Umberto Pizzano
Umberto Pizzano
Umberto Pizzano
Simona Piemontese
Gabriele Facchin
Raffaella Greco
Marta Lisa Battista
Jacopo Peccatori
Renato Fanin
Renato Fanin
Fabio Ciceri
Fabio Ciceri
Francesca Patriarca
Francesca Patriarca
Maria Teresa Lupo-Stanghellini
author_facet Umberto Pizzano
Umberto Pizzano
Umberto Pizzano
Simona Piemontese
Gabriele Facchin
Raffaella Greco
Marta Lisa Battista
Jacopo Peccatori
Renato Fanin
Renato Fanin
Fabio Ciceri
Fabio Ciceri
Francesca Patriarca
Francesca Patriarca
Maria Teresa Lupo-Stanghellini
author_sort Umberto Pizzano
collection DOAJ
description BackgroundThe introduction of posttransplant cyclophosphamide (PTCy) is one of the major achievements in the field of haploidentical stem cell transplantation (haplo-HCT). The transplant conditioning intensity (TCI) score is a refined classification of conditioning regimens that assigns weight scores to conditioning regimen components. The aim of our analysis was twofold: to assess the effect on transplant outcomes of combining PTCy with calcineurin inhibitor + mycophenolate mofetil (MMF) instead of mTOR inhibitor + MMF for GvHD prophylaxis, and to assess the effect of stratification by conditioning intensity in the setting of haplo-HCT.MethodsThis study was conducted in adult patients who underwent haplo-HCT at the University Hospital of Udine (UUH) or Ospedale San Raffaele (OSR) between January 2014 and December 2021. Patients received PTCy plus CsA-MMF at UUH and sirolimus-MMF at OSR. Conditioning intensity was defined by the TCI score. All data were collected prospectively.ResultsA total of 216 haplo-HCTs were performed, 81 at UUH and 135 at OSR. Notably, none of the patients at UUH received a high TCI score regimen compared to 72 (53.3%) at OSR. Our results show overlapping survival outcomes (OS, NRM, DFS, GRFS, and RI) within the two platforms. We observed a higher incidence of cGvHD within the sirolimus/MMF + PTCy platform, and high TCI was found to be the only risk factor for a higher incidence of grades III–IV aGvHD in univariate analysis.ConclusionOur results suggest that TCI may reveal the role of chemoradiotherapy in promoting conditions that may contribute to the occurrence of GvHD. The impact of moderate/severe cGvHD on quality of life must challenge our efforts to further optimise prophylactic strategies.
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spelling doaj-art-8a6e4b98751742369ae02ef389dec08f2025-08-20T03:05:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16103911610391Post-transplant cyclophosphamide in haploidentical stem cell transplantation: evaluating the impact of transplant conditioning intensityUmberto Pizzano0Umberto Pizzano1Umberto Pizzano2Simona Piemontese3Gabriele Facchin4Raffaella Greco5Marta Lisa Battista6Jacopo Peccatori7Renato Fanin8Renato Fanin9Fabio Ciceri10Fabio Ciceri11Francesca Patriarca12Francesca Patriarca13Maria Teresa Lupo-Stanghellini14Haematology and Stem Cell Transplantation Unit, University Hospital ASUFC, Udine, ItalyHaematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, ItalyHaematology and Bone Marrow Transplantation Unit, Cà Foncello Hospital, Treviso, ItalyHaematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, ItalyHaematology and Stem Cell Transplantation Unit, University Hospital ASUFC, Udine, ItalyHaematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, ItalyHaematology and Stem Cell Transplantation Unit, University Hospital ASUFC, Udine, ItalyHaematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, ItalyHaematology and Stem Cell Transplantation Unit, University Hospital ASUFC, Udine, ItalyDepartment of Medical Area (DAME), University of Udine, ItalyHaematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, ItalyUniversità Vita-Salute San Raffaele, Milan, ItalyHaematology and Stem Cell Transplantation Unit, University Hospital ASUFC, Udine, ItalyDepartment of Medical Area (DAME), University of Udine, ItalyHaematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, ItalyBackgroundThe introduction of posttransplant cyclophosphamide (PTCy) is one of the major achievements in the field of haploidentical stem cell transplantation (haplo-HCT). The transplant conditioning intensity (TCI) score is a refined classification of conditioning regimens that assigns weight scores to conditioning regimen components. The aim of our analysis was twofold: to assess the effect on transplant outcomes of combining PTCy with calcineurin inhibitor + mycophenolate mofetil (MMF) instead of mTOR inhibitor + MMF for GvHD prophylaxis, and to assess the effect of stratification by conditioning intensity in the setting of haplo-HCT.MethodsThis study was conducted in adult patients who underwent haplo-HCT at the University Hospital of Udine (UUH) or Ospedale San Raffaele (OSR) between January 2014 and December 2021. Patients received PTCy plus CsA-MMF at UUH and sirolimus-MMF at OSR. Conditioning intensity was defined by the TCI score. All data were collected prospectively.ResultsA total of 216 haplo-HCTs were performed, 81 at UUH and 135 at OSR. Notably, none of the patients at UUH received a high TCI score regimen compared to 72 (53.3%) at OSR. Our results show overlapping survival outcomes (OS, NRM, DFS, GRFS, and RI) within the two platforms. We observed a higher incidence of cGvHD within the sirolimus/MMF + PTCy platform, and high TCI was found to be the only risk factor for a higher incidence of grades III–IV aGvHD in univariate analysis.ConclusionOur results suggest that TCI may reveal the role of chemoradiotherapy in promoting conditions that may contribute to the occurrence of GvHD. The impact of moderate/severe cGvHD on quality of life must challenge our efforts to further optimise prophylactic strategies.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1610391/fullhaplo identical hematopoietic stem cell transplantationPTCy-haplo HSCTsirolimusGRFStransplant conditioning intensityGvHD
spellingShingle Umberto Pizzano
Umberto Pizzano
Umberto Pizzano
Simona Piemontese
Gabriele Facchin
Raffaella Greco
Marta Lisa Battista
Jacopo Peccatori
Renato Fanin
Renato Fanin
Fabio Ciceri
Fabio Ciceri
Francesca Patriarca
Francesca Patriarca
Maria Teresa Lupo-Stanghellini
Post-transplant cyclophosphamide in haploidentical stem cell transplantation: evaluating the impact of transplant conditioning intensity
Frontiers in Immunology
haplo identical hematopoietic stem cell transplantation
PTCy-haplo HSCT
sirolimus
GRFS
transplant conditioning intensity
GvHD
title Post-transplant cyclophosphamide in haploidentical stem cell transplantation: evaluating the impact of transplant conditioning intensity
title_full Post-transplant cyclophosphamide in haploidentical stem cell transplantation: evaluating the impact of transplant conditioning intensity
title_fullStr Post-transplant cyclophosphamide in haploidentical stem cell transplantation: evaluating the impact of transplant conditioning intensity
title_full_unstemmed Post-transplant cyclophosphamide in haploidentical stem cell transplantation: evaluating the impact of transplant conditioning intensity
title_short Post-transplant cyclophosphamide in haploidentical stem cell transplantation: evaluating the impact of transplant conditioning intensity
title_sort post transplant cyclophosphamide in haploidentical stem cell transplantation evaluating the impact of transplant conditioning intensity
topic haplo identical hematopoietic stem cell transplantation
PTCy-haplo HSCT
sirolimus
GRFS
transplant conditioning intensity
GvHD
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1610391/full
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