Pediatric-Specific Guidelines for Fever and Neutropenia: A Catalyst for Improving Care and Focusing Research

Open-ended hospitalization of chemotherapy patients who develop fever and neutropenia (FN pediatric cancers are very different from adult, with higher percentages of acute leukemias and brain tumors, and overall much higher intensity of therapy. In addition, physiologic differences (size, drug clearance, ability to tolerate sepsis) and inability to communicate in the youngest children give little room for error in clinical assessment. Any guideline focused on management of F&N in our youngest patients with cancer must tackle these challenging issues. In the article that accompanies this editorial, Lehrnbecher et al, an international panel of experts in infectious disease and pediatric cancer, used well-validated approaches for creating evidence-based guidelines to assemble pediatric-specific recommendations that have filled this major gap. Their task was not easy. The number of quality studies in pediatrics is limited and the scales for risk stratification are so varied that the group could not propose a unified approach. Instead, they suggested that approaches validated in specific regions (United States, South America, Europe, etc) could be considered for use by a given center in that region. Although this approach is unsatisfying, it is a start. Aside from the inability to establish a firm recommendation for uniform risk categorization, the remainder of the injunctions in the guidelines are reasonable and helpful, well laid out in a question-andanswer format. The work as a whole is useful and should become a foundational document for current practice. Most of the recommendations in the document are straightforward and can be put into use in any setting, private or academic, rural or urban. The first recommendation given in the document, however, comes to the heart of the challenge alluded to previously: “Adopt a validated risk stratification strategy and incorporate it into routine clinical management.” Readers are referred to six validated strategies and counseled that “the process of deriving prediction rules frequently overestimates their effectiveness in practice, so rules require validation.” Further qualification is presented regarding geographical location, local practices, systems, and approaches. In a larger academic setting, such validation can and should be performed for the strategy a given group chooses. Once validated, the screening tools can become standard practice for that center. This is more problematic in smaller, private pediatric oncology settings, where patient numbers are low and resources for internal validation of such approaches may be thin. Adoption of these approaches into such settings would possibly be more likely to succeed if based on results of future studies that compare the most promising approaches and provide further confidence of universal applicability of a given approach. The authors rightly want more to come from publication of these guidelines than more uniform practice. Equally important to the recommendations for therapeutic approaches outlined in this work is the effort the group made to define what are considered key research gaps (Table 2 of the article). Several recommendations for moving forward with research included by the authors are worth highlighting and expanding. At the top of the list is a high-risk stratification schema for pediatric F&N. This is a vital topic and deserves its position on the top of list. There is a lot more to infectious risk than “high” and “low.” Among patients in the high-risk categories, several patient subsets deserve particular attention and consideration, specifically children JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 30 NUMBER 35 DECEMBER 1