Impact of GVHD on relapse and non-relapse mortality following post-transplant cyclophosphamide-based transplantation.

BACKGROUND

Following conventional graft-versus-host disease (GVHD) prophylaxis, the development of acute and/or chronic GVHD is associated with lower relapse rates. However, the effects of GVHD on relapse and non-relapse mortality following post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis have not been well studied.

OBJECTIVE

To this end, we analyzed the impact of acute and chronic GVHD following PTCy-based haploidentical donor transplantation (HIDT).

STUDY DESIGN

The analysis included 335 consecutive HIDT recipients transplanted at a single institution between 2005 and 2021. Landmark analysis (LA) and time-dependent multivariable analysis (MVA) were utilized to study the impact of GVHD development on transplant outcome. Landmarks were defined as Day +100 for acute GVHD and one-year for chronic GVHD.

RESULTS

Recipient characteristics included a median age of 50 (19-80) years, most commonly transplanted for acute leukemia[/MDS [242]. PBSC was the graft source in 81%, and regimen intensity was myeloablative in 49%. Median follow-up was 65 (23-207) months. In landmark analysis, development of grade 3-4 acute GVHD (vs. 0-1) was associated with inferior 3-yr overall survival (OS 47% vs. 64%, p=0.041), due to higher NRM (25% vs. 10%, p=0.013). In contrast, development of grade 2 acute GVHD had no significant effect on NRM or survival. When restricted to acute leukemia/MDS patients, development of grade II acute GVHD was associated with improved OS (79% vs. 58%, p=0.027) and a trend towards lower relapse (24% vs. 36%, p=0.08). Development of moderate-to-severe chronic GVHD resulted in significantly higher NRM (15% vs. 4%, p=0.010), but had no impact on relapse, DFS or OS. In Cox multivariate analysis (MVA), grade 3-4 acute GVHD and moderate-to-severe chronic GVHD were both associated with significantly higher NRM (HR 3.38, p<0.001 and HR3.35, p<0.001, respectively). In addition, grade 3-4 acute GVHD predicted worse OS (HR 1.80, p=0.007) and DFS (HR 1.55, p=0.041). In contrast, relapse was not impacted by acute or chronic GVHD in MVA. Grade 2 acute GVHD was not associated with transplant outcome in MVA.

CONCLUSION

In summary, both grade 3-4 acute and moderate-to-severe chronic GVHD were associated with higher NRM after PTCy-based HIDT, without an effect on relapse risk. Methods of early identification of such patients in order to augment GVHD prophylaxis are clearly needed.

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of competing interest There are no competing financial interests in relation to the work described.