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Severe Sepsis in Hematopoietic Stem Cell Transplant Recipients*

Kumar, Gagan MD1; Ahmad, Shahryar MD2; Taneja, Amit MD1; Patel, Jayshil MD1; Guddati, Achuta Kumar MD, PhD3; Nanchal, Rahul MD1the Milwaukee Initiative in Critical Care Outcomes Research Group of Investigators

doi: 10.1097/CCM.0000000000000714
Clinical Investigations
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Objective: Severe sepsis requires timely management and has high mortality if care is delayed. Hematopoietic stem cell transplant recipients are more likely to be immunocompromised and are predisposed to serious infections. Reports of outcomes of severe sepsis in this population are limited to data from single, tertiary care centers, and national outcomes data are missing.

Design: Retrospective analysis of an administrative database.

Setting: Twenty percent of community hospitals in United States, excluding federal hospitals.

Subject: Patients with severe sepsis.

Intervention: None.

Measurements and Main Results: We used International Classification of Diseases, 9th Edition, Clinical Modification codes indicating the presence of sepsis and organ system failure to identify hospitalizations for severe sepsis between 2000 and 2008. We also used International Classification of Diseases, 9th Edition, Clinical Modification codes to identify hematopoietic stem cell transplant recipients. We compared outcomes of hematopoietic stem cell transplant recipients with severe sepsis during engraftment and subsequent admissions with a non–hematopoietic stem cell transplant cohort and excluded solid-organ transplantation from this cohort. We used mixed effect, multivariate logistic regression modeling with propensity score adjustment to examine factors associated with mortality of severe sepsis in hematopoietic stem cell transplant recipients. A total of 21,898 hematopoietic stem cell transplant recipients with severe sepsis were identified. The frequency of severe sepsis in hematopoietic stem cell transplant recipients was five times higher when compared with the non–hematopoietic stem cell transplant cohort. The unadjusted mortality was 32.9% in non–hematopoietic stem cell transplant cohort, which was similar to autologous hematopoietic stem cell transplant recipients (30.1%) and those who did not develop graft-versus-host disease (35%). Mortality was significantly higher in allogeneic transplants (55.1%, p < 0.001) and in those who developed graft-versus-host disease (47.9%, p < 0.001). After adjustment, during engraftment admission, the odds of in-hospital mortality in allogeneic hematopoietic stem cell transplant (odds ratio, 3.81; 95% CI, 2.39–6.07) and autologous hematopoietic stem cell transplant (odds ratio, 1.28; 95% CI, 1.06–1.53) recipients was significantly higher than non–hematopoietic stem cell transplant patients. Similarly, in subsequent admissions, hematopoietic stem cell transplant recipients with graft-versus-host disease (odds ratio, 2.14; 95% CI, 1.88–2.45) and without graft-versus-host disease (odds ratio, 1.35; 95% CI, 1.19–1.54) had significantly higher odds of mortality than non–hematopoietic stem cell transplant patients. Among patients with hematopoietic stem cell transplant, persons with autologous hematopoietic stem cell transplant and those without graft-versus-host disease fared better as compared with their allogeneic and graft-versus-host disease counterparts.

Conclusions: Hematopoietic stem cell transplant recipients are more likely to develop severe sepsis and die following a severe sepsis episode than nontransplant patients. Autologous hematopoietic stem cell transplant recipients and those who do not develop graft-versus-host disease have significantly better outcomes than allogeneic and graft-versus-host disease patients.

Supplemental Digital Content is available in the text.

1Department of Medicine, Division of Pulmonary and Critical Care Medicine, Medical College of Wisconsin, Milwaukee, WI.

2Department of Medicine, Division of Hospital Medicine, Medical College of Wisconsin, Milwaukee, WI.

3Department of Medicine, Division of Hospital Medicine, Massachusetts General Hospital, Boston, MA.

* See also p. 501.

Dr. Kumar designed the study, did statistical analysis, and wrote the article. Dr. Ahmad wrote the article. Drs. Taneja, Patel, and Guddati did critical review and revised the article. Dr. Nanchal designed the study, did statistical analysis, and wrote the article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

The authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: gagankumar@gmail.com

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