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. 2010 Dec 20;5(12):e15156.
doi: 10.1371/journal.pone.0015156.

Intestinal damage determines the inflammatory response and early complications in patients receiving conditioning for a stem cell transplantation

Walter J F M van der Velden  1 , Alexandra H E Herbers, Ton Feuth, Nicolaas P M Schaap, J Peter Donnelly, Nicole M A Blijlevens
Affiliations

Intestinal damage determines the inflammatory response and early complications in patients receiving conditioning for a stem cell transplantation

Walter J F M van der Velden et al. PLoS One. .

Abstract

Background: Stem cell transplantation (SCT) is still complicated by the occurrence of fever and inflammatory complications attributed to neutropenia and subsequent infectious complications. The role of mucosal barrier injury (MBI) of the intestinal tract therein has received little attention.

Methods: We performed a retrospective analysis in 163 SCT recipients of which data had been collected prospectively on intestinal damage (citrulline), inflammation (C-reactive protein), and neutrophil count. Six different conditioning regimens were studied; 5 myeloablative (MA) and 1 non-myeloablative (NMA). Linear mixed model multivariate and AUC analyses were used to define the role of intestinal damage in post-SCT inflammation. We also studied the relationship between the degree of intestinal damage and the occurrence of early post-SCT complications.

Results: In the 5 MA regimen there was a striking pattern of inflammatory response that coincided with the occurrence of severe intestinal damage. This contrasted with a modest inflammatory response seen in the NMA regimen in which intestinal damage was limited. With linear mixed model analysis the degree of intestinal damage was shown the most important determinant of the inflammatory response, and both neutropenia and bacteremia had only a minor impact. AUC analysis revealed a strong correlation between citrulline and CRP (Pearson correlation r = 0.96). Intestinal damage was associated with the occurrence of bacteremia and acute lung injury, and influenced the kinetics of acute graft-versus-host disease.

Conclusion: The degree of intestinal damage after myeloablative conditioning appeared to be the most important determined the inflammatory response following SCT, and was associated with inflammatory complications. Studies should explore ways to ameliorate cytotoxic therapy-induced intestinal damage in order to reduce complications associated with myeloablative conditioning therapy.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Course of citrulline and CRP in time after start of conditioning.
Five MA and one NMA conditioning regimens are shown; A = HDM, B = BEAM, C = Ida-Cyclo-TBI, D = Cyclo-ATG-TBI, E = Cyclo-TBI, F = Cyclo-Flu. Observed values (•), mean values (○).
Figure 2
Figure 2. Summary of the time course of citrulline (A) and CRP (B) for all 6 regimens.
Day 1 is the day of start of conditioning. To correct for unobserved citrulline and CRP values we modeled the course of citrulline and CRP as described in methods. 1 = HDM, 2 = BEAM, 3 = Ida-Cyclo-TBI, 4 = Cyclo-ATG-TBI, 5 = Cyclo-TBI, 6 = Cyclo-Flu. Mean CRP in mg/L, mean citrullline in µmol/L.
Figure 3
Figure 3. Pearson correlation between the mean degrees of neutropenia (NP in days) and inflammation (CRPAUC) versus intestinal damage (CitrullineAUC) and inflammation (CRPAUC) over the different regimens.
1 = HDM, 2 = BEAM, 3 = Ida-Cyclo-TBI, 4 = Cyclo-ATG-TBI, 5 = Cyclo-TBI, 6 = Cyclo-Flu.
See this image and copyright information in PMC

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