Patterns of C-reactive protein release following allogeneic stem cell transplantation are correlated with leukemic relapse

Abstract

The C-reactive protein (CRP) is an acute-phase protein produced by hepatocytes, and is a reliable marker of systemic inflammation, which is relevant to the release of the proinflammatory cytokines. The value of monitoring the CRP levels after stem cell transplantation (SCT) can identify patients at risk of treatment-related complications and mortality. Inflammatory cytokines facilitate donor T-cell activation via antigen presenting cells immediately after SCT. This study examined the relationship between the post-SCT CRP levels and a leukemic relapse. Fifty-four consecutively transplanted patients who relapsed after the allogeneic SCT were compared with nonrelapsing patients. The serum CRP levels were measured on day 0 and every 7 days thereafter until 4 weeks after the SCT. The mean CRP levels throughout the early post-SCT episode were significantly lower in the relapsing patients than in those who did not experience relapse (mean7s.e.: 26.876.3 vs 65.379.4 for first week, P ¼ 0.001; 23.973.8 vs 44.676.6 for second week, P ¼ 0.008). Univariate analysis showed that the CRP level on the first and second week, and graft-versus-host disease were significantly associated with a relapse. Multivariate analysis showed that the CRP level on the first week was the strongest independent variable predicting the risk of a relapse after SCT (P ¼ 0.04). These results indicate that the serum CRP levels early after allogeneic SCT might display the graft-versus-leukemia (GvL) effect. CRP is a surrogate of the proinflammatory cytokine release that was not measured in this study. The GvL effect appears to be efficiently strengthened by the high CRP levels that may be reflecting T-cell activation.

Change in serum proteome during allogeneic hematopoietic stem cell transplantation and clinical significance of serum C-reactive protein and haptoglobin

“…As these studies, our results suggest that not only the severity and multiplicity of precipitating causes, but also individual inflammatory response level, determine outcome during the 3 weeks after allo-HSCT. In addition, a correlation between CRP and leukemic relapse was found, wherein mean CRP level throughout the early post-SCT episode were significantly lower in relapsing patients than in others (Min et al, 2006). Also, GVHD was significantly associated with relapse.…”

Inflammatory Markers in Patients after Hematopoietic Stem Cell Transplantation

“…The CRP levels were measured weekly. In this study, the early rise of CRP after transplant may not only be a marker of GvHD but also the graft-versus-leukemia effect (Min et al 2006). Antigenactivated T cells are not only involved in GvHD and graft rejection, but also leukemia control and protection against infectious agents (Min et al 2006).…”

“…In this study, the early rise of CRP after transplant may not only be a marker of GvHD but also the graft-versus-leukemia effect (Min et al 2006). Antigenactivated T cells are not only involved in GvHD and graft rejection, but also leukemia control and protection against infectious agents (Min et al 2006). On the other hand, some authors report the lack of association between CRP levels and exclusive GvHD (Pihusch et al 2006;Saarinen et al 1987;Schwaighofer et al 1994).…”

“…When only patients receiving myeloablative conditioning were included, 25 % grade II-IV acute GvHD (aGvHD) were seen in the low-CRP group, and 58 % in the high-CRP group, 7 % grade III-IV in the low-CRP group and 21 % in the high-CRP group (Fuji et al 2008). In a study on leukemic relapse and its correlation with CRP levels, Min et al (2006) found that mean CRP levels on the first and second weeks after transplant were significantly higher in those with aGvHD and chronic GvHD than in those patients without GvHD (mean ± SE 72.3 ± 13.3 vs 35.7 ± 6.0 mg/L for first week; 57.7 ± 10.0 vs 24.8 ± 3.2 mg/L for second week). There were, however, no significant differences with regard to the CRP levels in these patient groups on the third and fourth weeks (mean ± SE 19.8 ± 3.8 vs 15.7 ± 2.2 mg/L for third week; 9.1 ± 2.1 vs 7.2 ± 0.9 mg/L for the fourth week).…”

Possible Implication of Bacterial Infection in Acute Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

“…Our group reported that a significant elevation of CRP during the neutropenic period was associated with a subsequent incidence of acute GVHD (50). Min et al also reported that patients with GVHD had a significantly higher CRP level early after allogeneic HSCT compared to those without GVHD (56). Furthermore, Michigan group assessed plenty of biomarkers to establish a biomarker panel for the prediction of acute GVHD (58).…”