Abstract

The C-reactive protein (CRP) is an acute phase protein that is released in response to inflammatory cytokines. An early increase in CRP following allogeneic and autologous stem cell transplant (SCT) has been shown to correlate with major transplant complications and transplant-related mortality (TRM). To date, there are no published reports documenting the impact of CRP levels prior to conditioning on outcomes after an allogeneic SCT. We thus collected pre-conditioning (PC) CRP data on 475 consecutive adult patients (>16 years of age) who received a first myeloablative allogeneic SCT for chronic myeloid (n=391) or acute leukemia (n=84) between January 1989 and October 2006. There were 228 sibling and 247 matched unrelated donors. CRP data were collected at a median of 16 days prior to stem cell infusion and were divided into 3 groups: < 2 mg/L (low, n=153), 2–9 mg/L (intermediate, n=239) and > 9 mg/L (high, n=83). Values > 9 mg/L are considered abnormal whereas values < 9mg/L are usually regarded as clinically insignificant. In univariate analysis, the 5 year probabilities of survival were 69% (low), 58% (intermediate) and 30% (high). When adjusted for patient age, disease stage, duration of disease prior to transplant, donor type (sibling versus unrelated), patient/donor sex and treatment era in a Cox multivariate analysis, a high PC CRP was associated with an increased risk of mortality when compared with the low PC CRP; relative risk (RR) 2.74 (95% CI 1.9–4.0). A high PC CRP was also associated with an increased risk of TRM; RR 3.3 (95% CI 2.1–5.4). However, there was no association with relapse; RR 0.94 (95% CI 0.6–1.6), nor with Grade 2–4 acute graft-versus-host disease (aGVHD); RR 1.1 (95% CI 0.6–2.1). No differences between the three CRP categories with respect to causes of death were observed, suggesting that an elevated CRP increases the risk of TRM in an indiscriminate manner. The intermediate CRP group had an increased risk of mortality (RR 1.3 [95% CI 0.9–1.8]) and TRM (RR 1.3 [95% CI 0.8–2.0]) when compared with the low group but this was not statistically significant. However, in the sibling donor cohort, the relative risks of mortality were 3.2 (95% CI 1.6–6.3) and 5.9 (95% CI 2.8–12.3) for the intermediate and high groups, whilst for the unrelated donor cohort, the relative risks were 0.9 (95% CI 0.6–1.4) and 2.1 (95% CI 1.3–3.4) respectively. Thus the impact of PC CRP is more significant in recipients of sibling donor transplants. In order to investigate infection as a potential cause of an increased PC CRP, patient records were reviewed for evidence of bacteremia. There was no significant difference between the 3 CRP groups: 0.7%, 1.3% and 1.2% respectively. In this study, we have demonstrated that an elevated PC CRP is predictive of decreased survival secondary to increased TRM, even in patients with an intermediate level PC CRP that would conventionally be considered clinically insignificant. We postulate that an increased PC CRP may reflect an underlying predisposition that results in a reduced ability to tolerate the stress of a stem cell transplant. In patients who have a high PC CRP, it may be prudent to investigate the etiology of the elevated CRP and consider delay of transplantation until the CRP normalises.

Author notes

Disclosure: No relevant conflicts of interest to declare.