Oct 27, 2003 - We note the recent report by Schots et al1 indicating that an early increase in C-reactive protein (CRP) is an indepen- dent risk factor for ...
Bone Marrow Transplantation (2004) 33, 121–122 & 2004 Nature Publishing Group All rights reserved 0268-3369/04 $25.00
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Correspondence Prognostic value of C-reactive protein and cytokine assays for transplant-related mortality Bone Marrow Transplantation (2004) 33, 121–122. doi:10.1038/sj.bmt.1704305 Published online 27 October 2003 We note the recent report by Schots et al1 indicating that an early increase in C-reactive protein (CRP) is an independent risk factor for transplant-related mortality (TRM) after allogenic BMT. While we would concur with the view that CRP elevation in the immediate post transplant period may signal an increased hazard level, it is unfortunate that pretransplant levels were not reported, as this may be more informative. Reviewing unpresented data from a previously described group of 23 patients2 receiving 24 autologous transplants between November 1994 and November 1996, we observed that pretransplant CRP levels were significantly higher in three patients who suffered TRM with an acute respiratory distress syndrome (ARDS)-like syndrome when compared to the remaining patients (Table 1; Po0.05, Mann– Whitney test). These differences had statistical significance irrespective of whether the values for CRP closest to the time of transplant (P ¼ 0.005), the prechemotherapy value (P ¼ 0.026) or the highest CRP level recorded at any time in the 7 days prior to the transplant (P ¼ 0.009) were used. In contrast, when the highest CRP level in the 5 days post transplant was used, the difference did not reach statistical significance (P ¼ 0.271). Two of the three ARDS patients had refractory non-Hodgkin’s lymphoma (NHL). One, a young woman, had a culture-negative febrile episode at the onset of BEAM therapy; she was unwell post transplant and developed ARDS on day 19. The second NHL patient was well throughout the procedure until he suddenly developed ARDS on day 9. The third patient was a young man with relapsed (and moderately responsive) germ cell tumour with pulmonary involvement and poorer general condition, although with no specific infection, who developed ARDS on day 5. We have also reviewed the data from this group of patients obtained from ELISA-based cytokine assays including IL-6 (data shown in Table 1), G-CSF,
Table 1
GM-CSF, TNF a, MIP-1 a, stem cell factor (SCF), serum leukocyte protease inhibitor (SLPI), IL-3 and IL-11. SCF, IL-3 and IL-11 were not detectable in the serum of any of the patients studied. TNF a, IL-6 and MIP-1 a were raised in all patients at some point during their transplant. There was a loose correlation between CRP and IL-6 values; pretransplant levels of IL-6 in the TRM group were higher than in the non-TRM group although the differences were not statistically significant and appeared unlikely to have clinical utility. No other cytokine showed any difference between the two groups. Although TRM has been reduced to 3% or less in standard risk autologous transplantation, ARDS remains a serious and regularly fatal complication,3 with a survival of only 10% in a large series of allogenic BMT in children.4 The utility of CRP as a predictive factor for serious complications of transplantation has been examined by other workers. Discrimination of prognostic groups using a normal, or near normal, categorisation appears to be largely unsuccessful5,6 or to produce a marginally discriminatory value.7 In contrast, the use of exact CRP values provides prognostic information whether one uses the pretransplant8 or post transplant levels9 in allogenic transplantation. Although IL-6 levels are related to CRP,10 the cytokine does not appear to provide useful information with regard to serious complications of transplantation, although it may be predictive of long-term prognosis.11 CRP is a routine, widely available and reproducible test. We suggest that, if these results can be confirmed in a larger prospective study, it may be possible to identify a relatively small group of patients whose TRM risk is high and who require particularly careful monitoring during the transplant procedure. There may even be a case for delaying transplantation in appropriate clinical circumstances until the cause of the raised CRP level has been identified and remedied where this is possible.
TCM Morris MK Magill L Ranaghan AE Irvine
Department of Haematology, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, Northern Ireland
CRP and IL-6 levels in patients undergoing autological phase transplantation
Time of CRP/1L-6 measurement
CRP prior to chemo for Tx (mg/l) CRP immediately prior to Tx (mg/l) CRP highest level before Tx (mg/l) CRP highest level post Tx (first 5 days) (mg/l) 1L-6 highest level before Tx (pg/ml) 1L-6 highest level post Tx (first 5 days) (pg/ml)
Survivors (n ¼ 21)
TRM’s (n ¼ 3)
Median
Range
Median
Range
P-value
5.5 13 20 30 60 90.5
0–26 0–60 1–80 2–300 0–300 0–320
47.5 60 300 185 155 300
25–70 45–75 45–300 30–230 45–170 45–300
0.026 0.005 0.009 0.271 0.659 0.536
Correspondence
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