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Abstract <p>Post-transplant cyclophosphamide (PTCy) has been explored as GvHD prophylaxis in matched related and unrelated donor transplants with encouraging outcomes, although at the cost of increased toxicity. A prospective, single-center study was conducted to assess the safety and efficacy of reduced-dose PTCy (15 or 25 mg/kg), combined with low-dose alemtuzumab and cyclosporin for GvHD prophylaxis, following 9/10 mismatched unrelated peripheral blood stem cell transplantation (MMUD PBSCT). Low-dose PTCy resulted in significantly reduced cumulative incidence (CI) of acute GvHD (aGvHD) grade II–IV and III–IV compared to control, without affecting relapse rates. Furthermore, the PTCy-group exhibited significantly lower non-relapse mortality (NRM), improved overall survival (OS) and GvHD-free/relapse-free survival (GRFS) (19% vs 45%, 63% vs 35% and 48% vs 25% for PTCy and control groups, respectively). PTCy-15 subgroup exhibited significantly increased NRM compared to PTCy-25 subgroup. However, this effect was counterbalanced by a significant decrease in the CI of relapse, overall resulting in similar OS and GRFS between the two subgroups. This is one of the first studies showing not only the efficacy of low-dose PTCy in GvHD prevention in the MMUD allo-PBSCT setting, but also the ability to tailor PTCy dosing based on relapse risk, allowing for a personalized approach to GvHD prevention.</p> Key points <p><UnorderedList Mark="Bullet"> <ItemContent> <p>Low-dose PTCy is associated with significantly reduced rates of aGvHD and improved survival outcomes, without increased relapse rates.</p> </ItemContent> <ItemContent> <p>PTCy dose of 25 mg/kg is associated with very low NRM, whereas the 15 mg/kg dose has low relapse rates supporting a risk-adapted approach</p> </ItemContent> </UnorderedList></p> <p></p>

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Low-dose post-transplant cyclophosphamide in combination with low-dose alemtuzumab for graft-versus-host-disease prevention in mismatched unrelated allogeneic stem cell transplantation is associated with improved outcomes and reduced toxicity

  • 期刊论文

  • 发表日期：

    2025年10月23日

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  • Ioanna Lazana,
  • Konstantinos Gkirkas,
  • Ioannis Konstantellos,
  • Chrisovalanto Chatzidimitriou,
  • Aggeliki Karagiannidou,
  • Georgia Gkolfinopoulou,
  • Maria Stamouli,
  • Spiros Chondropoulos,
  • Panagiotis Tsirigotis

摘要

Abstract

Post-transplant cyclophosphamide (PTCy) has been explored as GvHD prophylaxis in matched related and unrelated donor transplants with encouraging outcomes, although at the cost of increased toxicity. A prospective, single-center study was conducted to assess the safety and efficacy of reduced-dose PTCy (15 or 25 mg/kg), combined with low-dose alemtuzumab and cyclosporin for GvHD prophylaxis, following 9/10 mismatched unrelated peripheral blood stem cell transplantation (MMUD PBSCT). Low-dose PTCy resulted in significantly reduced cumulative incidence (CI) of acute GvHD (aGvHD) grade II–IV and III–IV compared to control, without affecting relapse rates. Furthermore, the PTCy-group exhibited significantly lower non-relapse mortality (NRM), improved overall survival (OS) and GvHD-free/relapse-free survival (GRFS) (19% vs 45%, 63% vs 35% and 48% vs 25% for PTCy and control groups, respectively). PTCy-15 subgroup exhibited significantly increased NRM compared to PTCy-25 subgroup. However, this effect was counterbalanced by a significant decrease in the CI of relapse, overall resulting in similar OS and GRFS between the two subgroups. This is one of the first studies showing not only the efficacy of low-dose PTCy in GvHD prevention in the MMUD allo-PBSCT setting, but also the ability to tailor PTCy dosing based on relapse risk, allowing for a personalized approach to GvHD prevention.

Key points

Low-dose PTCy is associated with significantly reduced rates of aGvHD and improved survival outcomes, without increased relapse rates.

PTCy dose of 25 mg/kg is associated with very low NRM, whereas the 15 mg/kg dose has low relapse rates supporting a risk-adapted approach