Tool Might Help Predict Adverse Events in Children With Cancer

Janis C. Kelly

April 01, 2010

April 1, 2010 — Cancer patients who develop chemotherapy-induced febrile neutropenia (FN) are at risk for invasive infections, so standard treatment is emergency hospitalization and intravenous antimicrobial therapy. But patients could be spared this treatment if it were possible to identify those who were at low risk.

New risk-adapted treatment guidelines have been developed for adults, but so far no consensus has emerged on how to predict adverse-event (AE) risk in pediatric patients. A step toward this, however, is a new risk-scoring system, developed by Roland A. Ammann, MD, and colleagues in the Swiss Pediatric Oncology Group (SPOG), and reported online March 15 in the Journal of Clinical Oncology.

Dr. Ammann, from the Department of Pediatric Hematology/Oncology at the University of Bern in Switzerland, collaborated with oncologists from 8 medical centers in Switzerland and Germany to develop the new AE predictive measure. Their prospective SPOG 2003 FN study included cancer patients 1 to 18 years of age presenting with FN after nonmyeloablative chemotherapy. They analyzed 423 episodes of FN in 206 patients.

At presentation, patients underwent physical examination, complete blood count (including differential leukocyte count), and blood cultures, and were hospitalized and treated with empirical intravenous broad-spectrum antimicrobial therapy. Other procedures were determined by the treating physician.

After 8 to 24 hours of inpatient therapy, each patient was reassessed by a board-certified pediatric oncologist.

AEs were reported until 7 days after the discontinuation of antimicrobial therapy and the resolution of severe neutropenia.

The 4 variables that were useful for predicting AEs were preceding chemotherapy more intensive than acute lymphoblastic leukemia maintenance (weight = 4), hemoglobin of 90 g/L or more (weight = 5), leukocyte count of less than 0.3 g/L (weight = 3), and platelet count of less than 50 g/L (weight = 3). The score was the sum of these weights.

The score calculated at presentation did not accurately predict subsequent AEs, but patients with a score of 9 or more at reassessment (after 8 to 24 hours of hospital care) were at increased risk for future AEs.

The researchers tested this score against other published risk-prediction rules and found that it was more accurate. Overall sensitivity was 92%, with 35% of episodes classified as low risk. Specificity was 45%, and negative predictive value was 93%.

Adding differential leukocyte count data did not improve predictive accuracy.

The authors conclude that the "risk score developed here is constructed using 4 characteristics easily accessible, based on patient history and a blood cell count at presentation, but not on a differential leukocyte count. The prediction of risk for future AEs at reassessment, after 24 hours or less of inpatient management, is better than that at presentation with FN. This score accurately identifies patients at high risk for future AEs."

However, the score predicted only 1 of the 3 fatal AEs in the study population. One of these fatalities had a prediction score of 5, one had a score of 4, and one had a score of 10.

To comment on the study, Medscape Oncology asked Stephane Paulus, MD, who has also studied FN in children with cancer (Adv Exp Med Biol. 2009;634:185-204). Dr. Paulus, who is a pediatric infectious diseases consultant at Alder Hey Children's Hospital in Liverpool, United Kingdom, said; "This is another good attempt at trying to define as safely as possible a low-risk group of children with febrile neutropenia by a group with good experience in this field."

Dr. Paulus noted that although a pediatric oncologist reviewed the children at 8 to 24 hours, this was not accompanied by a second check of the inflammatory markers, in this case C-reactive protein (CRP).

"Other studies have shown the promise of using a combination of inflammatory markers, such as PCT (packed cell volume of platelets) and interleukin-8, in addition to CRP, at admission and then again at 24 hours (as these markers take time to 'react') to help define low- and high-risk groups. Including these markers along with a repeat clinical examination might have enhanced the study results," Dr. Paulus said.

"They conclude that their scoring system adequately predicts AEs. However, sensitivity was 92% and the positive predictive value was 40%. So the study was pretty decent at picking up those low risks but not [as good] at predicting the AEs correctly. But again, the score predicted AEs in only 1 of 3 episodes leading to death reported in this study," Dr. Paulus added.

Dr. Ammann stressed the importance of prospective validation studies before considering broad clinical application of this AE predictive score. According to Dr. Paulus, the score is somewhat useful but not accurate enough to safely identify a low-risk group in clinical practice.

"This does add some good data to the body of literature but does not revolutionize it," Dr. Paulus said.

The study was supported by Dr. Ammann and Christoph Aebi, MD, from the University Children's Hospital in Bern, Switzerland. Dr. Ammann and Dr. Paulus have disclosed no relevant financial relationships.

J Clin Oncol. Published online March 15, 2010. Abstract

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