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. 2025 Aug 15:16:1610391.
doi: 10.3389/fimmu.2025.1610391. eCollection 2025.

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

Umberto Pizzano  1   2   3 , Simona Piemontese  2 , Gabriele Facchin  1 , Raffaella Greco  2 , Marta Lisa Battista  1 , Jacopo Peccatori  2 , Renato Fanin  1   4 , Fabio Ciceri  2   5 , Francesca Patriarca  1   4 , Maria Teresa Lupo-Stanghellini  2
Affiliations

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

Umberto Pizzano et al. Front Immunol. .

Abstract

Background: The 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.

Methods: This 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.

Results: A 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.

Conclusion: Our 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.

Keywords: GRFS; GvHD; PTCy-haplo HSCT; haplo identical hematopoietic stem cell transplantation; sirolimus; transplant conditioning intensity.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor MS declared a past co-authorship with the authors RG and FC.

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