Levels of C-reactive protein and body temperature elevation during neutropenia predict engraftment and non-relapse mortality for unrelated single-unit cord blood transplantation in adults.

Abstract

BACKGROUND Cord blood transplantation (CBT) presents unique challenges related to inflammation during neutropenia, such as mucosal damage, infections, and the potential development of pre-engraftment syndrome or pre-engraftment immune reaction. These factors can contribute to significant inflammation and infection shortly after CBT. However, the effect of severe inflammation during neutropenia, specifically elevated C-reactive protein (CRP) level and body temperature, on post-transplant outcomes after CBT remains unclear. OBJECTIVE This retrospective study aimed to investigate the association between maximum CRP level, maximum body temperature during neutropenia, and post-transplantation outcomes in adult patients undergoing single-unit CBT. STUDY DESIGN We retrospectively evaluated the impact of maximum CRP level and maximum body temperature during neutropenia on post-transplantation outcomes in adults who underwent single-unit unrelated CBT between 1998 and 2023 at our institution. RESULTS A total of 336 adult patients were included in this study. The median maximum CRP level before neutrophil recovery was 7.75 mg/dL (interquartile range [IQR], 4.70 to 12.05 mg/dL) at a median of 14 days (IQR, 8 to 16 days). The median maximum body temperature before neutrophil recovery was 39.5°C (IQR, 39.0 to 40.0°C) at a median of 15 days (IQR, 12 to 17 days). In the multivariate analysis, a maximum CRP level≥20 mg/dL was significantly associated with lower neutrophil recovery (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.23 to 0.59; P<0.001), lower platelet recovery (HR, 0.28; 95% CI, 0.16 to 0.48; P<0.001), and a higher incidence of veno-occlusive disease/sinusoidal obstruction syndrome (HR, 16.42; 95% CI, 4.11 to 65.54; P<0.001), which resulted in higher non-relapse mortality (NRM) (HR, 5.16; 95% CI, 2.62 to 10.15; P<0.001) and worse overall survival (HR, 2.81; 95% CI, 1.66 to 4.78; P<0.001). Similarly, a maximum body temperature≥40.5°C was significantly associated with lower neutrophil recovery (HR, 0.51; 95% CI, 0.33 to 0.79; P=0.002), lower platelet recovery (HR, 0.55; 95% CI, 0.38 to 0.79; P=0.001), higher incidence of grades III to IV acute GVHD (HR, 2.93; 95% CI, 1.24 to 6.88; P=0.013), and extensive chronic GVHD (HR, 2.47; 95% CI, 1.22 to 4.97; P=0.011), which resulted in higher NRM (HR, 3.43; 95% CI, 1.53 to 7.67; P=0.002). CONCLUSION Maximum CRP level and maximum body temperature during neutropenia were significantly associated with lower hematopoietic recovery and higher NRM following single-unit CBT in adults. Further studies are warranted to explore early intervention strategies aimed at preventing severe inflammation and improving post-transplant outcomes in single-unit CBT.