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Re: Febrile neutropenia : transition towards a risk-directed approach

Dear Editor,

Phillips et al have appropriately brought to light the lack of consistency in treatment of chemotherapy induced febrile neutropenia in children.(1) We agree with the authors that formulation of a national guideline will help to simplify and streamline the approach to this common problem in paediatric oncology.

The authors have suggested that it may be possible to treat some children with antibiotic regimens of reduced intensity and duration, based on risk stratification. However, most such studies quoted were based on adult data. The few paediatric studies mentioned did not yield sufficient data for formulating a clear cut risk assessment scheme. In this regard, it might be worth pointing out that a recent extensive study in children has proposed and validated an objective risk assessment scoring system based on simple parameters.(2) This study identified 'low', 'intermediate' and 'high' risk groups, with the latter two carrying a relative risk of 13 -fold and 50-fold respectively, for severe infectious complications.

Uniformity is also required with regard to the choice of antibiotics according to risk. Most units in UK use a combination of a beta lactam antibiotic with an aminoglycoside for the treatment of febrile neutropenia. However, recent studies have demonstrated the relative efficacy and safety of monotherapy with cefepime, a fourth generation cephalosporin.(3) It has also been shown that lower risk febrile neutropenias can be successfully treated with an initial brief period of intravenous antibiotics, followed by 'stepping down' to oral ciprofloxacin or cefixime.(4,5) It should be noted that cefepime, although in common use in USA, is yet to be licensed for use in children in UK. The lack of similar randomised trials from UK seems to be the limiting factor in initiating a change of practice among paediatricians in favour of less intense therapy. However, such a shift will have significant positive impact on various parameters including cost effectiveness, turnover of in- patient beds, length of hospital stay, reduced toxicity from treatment and elimination of the need for aminoglycoside level monitoring. Monotherapy is also known to reduce the potential for emergence of drug resistant bacteria, as opposed to a combination of antibiotics.

It is hoped that the new unified guideline being prepared by United Kingdom Childrens Cancer Study Group (UKCCSG) in collaboration with Paediatric Oncology Nurses Forum (PONF) will attempt to address and clarify these issues. In view of the substantial number of children with neutropenic fever and the centralisation of care in tertiary paediatric oncology units, a national study specifically looking at these aspects seems quite feasible. This may provide the basis for changing the current practice of over thirty years in favour of a new evidence based and risk- directed approach.

References:

(1) Phillips R, Skinner R, Chisholm JC. Treating low risk febrile neutropaenia : Jenny's story. Arch Dis Child 2007; 92 : 7-8.

(2) Rondinelli PI, Kde CR, de Camargo B. A proposed score for predicting severe infection complications in children with chemotherapy induced febrile neutropenia. J Pediatr Hematol Oncol 2006; 28(10) : 665- 670.

(3) Ariffin H, Ai CL, Lee CL, Abdullah WA. Cefepime monotherapy for treatment of febrile neutropenia in children. J Paediatr Child Health 2006; 42(12) : 781-784.

(4) Paganini H, Rodriguez-Brieshcke T, Zubizaretta P. Oral ciprofloxacin in the management of children with cancer with lower risk febrile neutropenia. Cancer 2001; 91(8) : 1563-1567.