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Pre-engraftment blood stream infection is a risk factor for acute GVHD grades II–IV

Bone Marrow Transplantation volume 48, pages 1583–1584 (2013)Cite this article

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Pre-engraftment blood stream infection (BSI) is a common and serious complication of allogeneic hematopoietic SCT (HSCT).1 Besides the direct effects, BSI has long been suspected of being a risk factor for the subsequent development of acute GVHD (aGVHD). This association was recently proven for the first time in a study by Poutsiaka et al.2 The authors found that BSI occurring between the initiation of the conditioning regimen and 10 days after stem cell infusion was significantly associated with an increased risk of aGVHD II–IV before day 100, with cause-specific hazard ratios (HR) of 2.17. There were, however, some important limitations connected to the study; only 211 patients were included, the number of BSI before day 10 was low (n=28), and the association was at the borderline of statistical significance (P=0.04, 95% confidence interval, CI=1.05–4.49).

We retrospectively investigated risk factors for aGVHD grades II–IV before day 100, including pre-engraftment BSI, in 521 transplantations performed at our center between 2001 and 2008. The study was approved under the ethical permit DNR 425/97, issued by the ethics committee, Karolinska Institutet. In short, 514 consecutive patients undergoing 543 allogeneic HSCT were screened. The inclusion criterion of neutropenia was met in 521 transplantations performed in 493 patients (Table 1). All data except BSI had been collected in a prospective manner and entered in a database for research purposes. Bacterial prophylaxis with 500 mg ciprofloxacin twice daily was started 1 day before the transplantation and continued until engraftment. In the event of fever, defined as a temperature ⩾38.5 °C once or ⩾38.0 °C twice within 24 h, the blood cultures were drawn and empirical antibiotic therapy was instituted. The pre-engraftment phase was defined as the time from the transfusion of hematopoietic stem cells until resolution of neutropenia (ANC<0.5 × 109/L). BSI was defined as isolation of a bacterial or fungal pathogen from at least one set of blood cultures (one aerobic and one anaerobic bottle) drawn from a neutropenic patient after the start of the conditioning regimen. For coagulase-negative staphylococci and corynebacteria, isolation from at least two set of blood cultures with the same antibiogram were required. aGVHD was graded according to standard criteria.3 Predictive analyses for aGVHD II–IV were based on the proportional hazard model for subdistribution of competing risk. A stepwise backward procedure was used to construct a set of independent predictors for each end point. All predictors with a P-value below 0.10 in the univariate analysis were considered and sequentially removed if the P-value in the multiple models was above 0.05. All tests were two-sided. Analyses were performed using the S-Plus and Statistica software (StatSoft, Tulsa, OK, USA). The Mann–Whitney U-test was used to compare continuous variables and the χ2-test was used to compare the distribution of categorical variables.

Table 1 Patient and donor characteristics
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Authors and Affiliations

  1. Division of Infectious Diseases, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

    O Blennow

  2. Division of Therapeutic Immunology, Karolinska Institutet, Stockholm, Sweden

    O Blennow, J Mattsson & M Remberger

  3. Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Stockholm, Sweden

    J Mattsson & M Remberger

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  1. O Blennow
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  2. J Mattsson
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Correspondence to O Blennow.

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Blennow, O., Mattsson, J. & Remberger, M. Pre-engraftment blood stream infection is a risk factor for acute GVHD grades II–IV. Bone Marrow Transplant 48, 1583–1584 (2013). https://doi.org/10.1038/bmt.2013.103

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