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AAP Grand Rounds 21:6 (2009)
© 2009 American Academy of Pediatrics

Risk of Death After Hematopoietic Stem Cell Transplantation

The objective of the current study was to analyze intensive care unit (ICU) mortality trends and the main prognostic factors associated with hospital death in pediatric hematopoietic stem cell transplantation (HSCT, also known as bone marrow transplant) recipients.

PICO Question: Have mortality rates changed for children who require intensive care unit care after hematopoietic stem cell transplantation? Question type: Prognosis Study design: Systematic review with meta-regression

 

Need for ICU care after HSCT has historically been associated with high mortality rates. Whether ICU mortality for HSCT recipients has improved with better support methods is controversial.^1–3

Investigators from the Wilhelmina Children’s Hospital and Utrecht University in the Netherlands performed a comprehensive literature search in articles published through August 2006 on ICU mortality trends following HSCT and factors associated with death. Because of the heterogeneity of reported ICU mortality rates, a multiple random-effects meta-regression analysis was conducted to assess the independent contribution of prognostic factors on mortality.

Of 187 potential articles, 23 reporting on 1,101 ICU admissions included sufficient information to calculate ICU death rates and risk factors for death. Risk factors included age, need for mechanical ventilation, pulmonary disease, presence of multiple organ failure, presence and grade of graft versus host disease (GVHD), receipt of renal support therapy, presence of liver failure, type of transplantation (ie, allogenic or autologous), and underlying condition (eg, cancer).

Reported mortality rates for children requiring ICU care after HSCT varied widely (25%–91%) and decreased over time (from 80–90% in studies spanning 1988–1995 to 30–70% in studies from 2003–2006). Between 4% and 30% of children treated with HSCT required mechanical ventilation; for these children mortality ranged from 25% to 91% (mean 71%). In more recent years, significantly fewer ICU-admitted patients received mechanical ventilation. Factors associated with mortality following HSCT included year of study publication, median year of patient enrollment, and receipt of mechanical ventilation. Receipt of renal support therapy (P=.06) and pulmonary disease (P=.08) tended to be associated with ICU death. In the multiple meta-regression analysis, only pulmonary disease remained significantly associated with mortality (OR=1.21; 95% CI, 1.01–1.46).

The authors caution that the characteristics of patients admitted to the ICU after HSCT significantly changed over time and that survival in patients with respiratory disease may not be improving.

Commentary by Susan L. Bratton, MD, MPH, FAAP

Pediatric Critical Care Medicine, Primary Children’s Medical Center, University of Utah Health Sciences Center, Salt Lake City, UT

 
Dr. Bratton has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/devices

Key Words: human stem cell transplantation • mortality trends • prognosis

Indications for HSCT are increasing in children, and now include immune and metabolic disorders, blood dyscrasias, and hematogenous cancers.⁴ Organ toxicity is estimated to account for 6–10% of deaths after HSCT while acute infections lead to death in another 8–20%. ⁵

Reports from the late 1990s suggested that mortality following HSCT was decreasing¹ and might be attributed to better support methods such as low tidal volume mechanical ventilation or early use of continuous renal replacement therapy.²

However, in van Gestel, et al’s report the improved survival among children with HSCT requiring ICU care is largely related to fewer cases of respiratory failure rather than improved survival among those treated for respiratory failure.

This finding is similar to that recently reported using US hospital discharge data comparing children receiving HSCT in 1997, 2000, and 2003.⁶ The number of patients with sepsis, need for mechanical ventilation, or GVHD all significantly decreased over these years. Receipt of mechanical ventilation after HSCT declined from 9% in 1997 to 6% in 2003. Overall hospital death declined from 12% in 1997 to 6% in 2003.

However, mechanical ventilation, sepsis, and receipt of dialysis were all strongly associated with death. Only 36% of children who received mechanical ventilation survived to hospital discharge.

Improved supportive care with shorter engraftment time, better antimicrobial prophylaxis during periods of neutropenia, improved monitoring for subclinical infections, and less toxic conditioning regimens may account for decreased infections and less organ toxicity. ⁴ Better molecular HLA matching, altered immunosuppression regimens, and greater use of cord blood as a stem cell source likely explain lower rates of GVHD. However, among patients who develop organ failure, particularly respiratory failure after HSCT, risk of death remains high, and candid discussions with the patient and family regarding prognosis should occur. Many advances in ICU care lie in preventing complications rather than in treating them.

References

1. Rossi R, et al. Crit Care Med. 1999;27:1181–1186.[CrossRef][Medline]
2. DiCarlo JV, et al. J Pediatr Hematol Oncol. 2003;25:801–805.[CrossRef][Medline]
3. Keenan HT, et al. Crit Care Med. 2000;28:830–835.[CrossRef][Medline]
4. Copelan ED. N Engl J Med. 2006;354:1813–1826.[Free Full Text]
5. Center for International Blood and Marrow Transplant Research. http://www.cibmtr.org/SERVICES/Observational_Research/Summary_Slides/index.html. Accessed October 29, 2008.
6. Bratton SL, et al. Crit Care Med. 2008;36:923–927.[Medline]

This Article Extract Full Text (PDF) Take the CME quiz: Vol. 21 No. 1, January 2009 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bratton, S. L. Search for Related Content PubMed Articles by Bratton, S. L.