Monitoring of C-reactive protein after allogeneic bone marrow transplantation identifies patients at risk of severe transplant-related complications and mortality

Schots, Rik; Kaufman, Leonard; Riet, Ivan Van; Lacor, Patrick; Trullemans, Fabienne; Waele, Marc De; Camp, Ben Van

doi:10.1038/sj.bmt.1701286

Cited by 47 publications

(35 citation statements)

References 11 publications

(14 reference statements)

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“…7 We have previously shown that high peak levels of CRP were associated with the occurrence of MTC. 8 In this study, we demonstrate that an early increase of CRP-levels, before day 10 after BMT, is highly predictive of MTC and TRM before day 100 post-BMT.…”

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confidence: 77%

An early increase in serum levels of C-reactive protein is an independent risk factor for the occurrence of major complications and 100-day transplant-related mortality after allogeneic bone marrow transplantation

Schots

Riet

Othman³

et al. 2002

Bone Marrow Transplant

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Summary:We monitored levels of C-reactive protein (CRP) in 96 consecutive adult allogeneic BMT patients (age 15-50 years) transplanted in our unit. Major transplantrelated complications (MTC) occurred in 32% of cases and included: hepatic veno-occlusive disease, pneumonitis, severe endothelial leakage syndrome and >II acute GVHD. Transplant-related mortality (TRM) before day 100 post-BMT was 13.5%. Variables included in a stepwise logistic regression model were: gender, age, disease category, donor type, T cell depletion, TBI, use of growth factors, bacteremia, mean CRP-levels >50 mg/l between days 0 and 5 (CRP day 0-5) and >100 mg/l between days 6 and 10 (CRP day 6-10) post-BMT. Only high CRP-levels (for MTC and TRM) (P < 0.001) and donor-type (for TRM) (P ‫؍‬ 0.02) were independent risk factors. The estimated probability for MTC was 73% (CRP day 6-10 >100 mg/l) vs 17% (CRP day 6-10 <100 mg/l). Using the same cut-off levels, the probabilities for TRM were 36.5% vs 1% in the identical sibling donor situation and 88% vs 12.5% in other donor-type transplants. We conclude that the degree of systemic inflammation, as reflected by CRP-levels, during the first 5-10 days after BMT identifies patients at risk of MTC and TRM. Our data may be useful in selecting patients for clinical trials involving pre-emptive antiinflammatory treatment. Bone Marrow Transplantation (2002) 30, 441-446. doi:10.1038/sj.bmt.1703672 Keywords: C-reactive protein; severe complications; transplant-related mortality; allogeneic BMT Despite improvements in supportive care, the practice of allogeneic BMT remains limited by its toxicity. Overall

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confidence: 77%

An early increase in serum levels of C-reactive protein is an independent risk factor for the occurrence of major complications and 100-day transplant-related mortality after allogeneic bone marrow transplantation

Schots

Riet

Othman³

et al. 2002

Bone Marrow Transplant

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“…Elevation of the CRP can be used as an early marker of transplant-related complications, with a very high CRP being predictive of severe transplant-related complications and mortality. 18 We have found daily in-patient monitoring of CRP to be beneficial as an early marker for infection, with changes in the CRP sometimes predating fever or other clinical symptoms (Marks, unpublished data). An elevated CRP in a BMT patient attending for follow-up usually prompts us to perform an infection screen and, again, this has led to a diagnosis of bacteraemia in asymptomatic patients.…”

Section: Discussionmentioning

confidence: 99%

Gram-negative bacteraemia (GNB) after 428 unrelated donor bone marrow transplants (UD-BMT): risk factors, prophylaxis, therapy and outcome

Mitchell

Derrington

Turner

et al. 2003

Bone Marrow Transplant

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Summary:Gram-negative infection is an important cause of morbidity and mortality after unrelated donor-bone marrow transplantation (UD-BMT). We performed a retrospective case-control study to examine the risk factors, prophylaxis, therapy and outcome of Gram-negative bacteraemia (GNB) in 428 patients undergoing UD-BMT. The incidence of GNB was 3.6% in children and 19% in adults. Of the adults, 11% developed GNB 460 days post UD-BMT. Predisposing risk factors for GNB included 'high-risk' disease status, chronic graft-versushost disease and use of systemic steroids. Fever, a raised C-reactive protein (CRP) and hypotension were common findings at presentation. Patients were routinely given prophylactic ciprofloxacin: resistance to this antibiotic was seen in 33% of isolates. We identified an age-matched control group undergoing UD-BMT over the same time period as the study group. Gram-positive bacteraemia was significantly more common in cases than controls. Mortality from GNB was 17% in children and 24% in adults. We conclude that GNB is a common complication of UD-BMT with a high associated mortality. Patients should be educated further to present rapidly with symptoms suggestive of infection.

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“…4 We have previously shown that high levels of C-reactive protein (CRP) are associated with the occurrence of major transplant-related complications (MTCs), including severe AGVHD, VOD, ELS and pneumonitis. 5 CRP is an acute-phase protein produced by hepatocytes and is a reliable marker of systemic inflammation. 6 The inflammatory response in humans is characterized by the systemic release of proinflammatory cytokines including interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor (TNF)-alpha.…”

Section: Introductionmentioning

confidence: 99%

Proinflammatory cytokines and their role in the development of major transplant-related complications in the early phase after allogeneic bone marrow transplantation

et al. 2003

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Serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor (TNF)-alpha were frequently measured during the first 30 days after allogeneic bone marrow transplantation (BMT) in 84 consecutive adult patients. Major transplant-related complications (MTCs) occurred in 33% of cases and included veno-occlusive liver disease, idiopathic pneumonia syndrome, severe endothelial leakage syndrome and 4grade II acute graft-versus-host disease. Compared with patients having minor complications, those with MTCs developed higher levels at times of maximal clinical signs (all cytokines, Po0.001), between days 0-5 post-BMT (IL-6 and IL-8, Po0.05) and days 6-10 (L-6, Po0.001; IL-8 and TNF, Po0.01) post-BMT. We could not discriminate patterns of cytokine release that were specific for any subtype of MTC. Higher levels of IL-8 during days 0-5 were associated (P ¼ 0.044) with early (o40 days) death. Multivariate analysis including patient and transplant characteristics as well as post-BMT levels of C-reactive protein showed that high average levels of one or more of the cytokines within the first 10 days post-BMT were independently associated with MTC (Odd's ratio: 2.3 [1.2-4.5], P ¼ 0.011). This study shows that systemic release of proinflammatory cytokines contributes to the development of MTC and provides a rationale for pre-emptive anti-inflammatory treatment in selected patients.

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Monitoring of C-reactive protein after allogeneic bone marrow transplantation identifies patients at risk of severe transplant-related complications and mortality

Cited by 47 publications

References 11 publications

An early increase in serum levels of C-reactive protein is an independent risk factor for the occurrence of major complications and 100-day transplant-related mortality after allogeneic bone marrow transplantation

An early increase in serum levels of C-reactive protein is an independent risk factor for the occurrence of major complications and 100-day transplant-related mortality after allogeneic bone marrow transplantation

Gram-negative bacteraemia (GNB) after 428 unrelated donor bone marrow transplants (UD-BMT): risk factors, prophylaxis, therapy and outcome

Proinflammatory cytokines and their role in the development of major transplant-related complications in the early phase after allogeneic bone marrow transplantation

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