Febrile aplasia is a common occurrence in children/adults treated with chemotherapy for
malignant blood diseases or solid cancers.
This acquired deficiency of immunity mainly causes susceptibility to bacterial and fungal
infections, pathogens normally recognized by specific receptors of innate immunity
(Pattern Recognition Receptor, PRR).
Thus, the febrile episodes in the context of post-chemotherapy neutropenia can be
bacterial or fungal etiology, but can also frequently be related to viral infections,
toxic phenomena or other etiologies. In the absence of a discriminating marker, treatment
for all these children is based on early, broad-spectrum antibiotic therapy in hospital.
Septic shock or even death by refractory septic shock remain, even if they are rare, real
complications in pediatric oncology, requiring discriminatory markers for effective
management, While trying to reduce the number and duration of hospitalizations for
children at low risk for severe febrile aplasia.
It is therefore necessary to identify other markers allowing the earliest possible
classification of episodes of febrile aplasia.
A previous study, conducted by our team, PTX3 and febrile aplasia, studied pentraxin 3
(PTX3), a soluble PRR of the pentraxin family that plays a key role in immune
surveillance against pathogens. Preliminary results obtained from samples from a cohort
of patients treated in adult hematology and pediatric onco-hematology support a
prognostic character of PTX3 in the severity of aplasia, with higher elevations of serum
protein during episodes of severe sepsis or septic shock (ongoing analyses and
interpretations for the adult population). The available data to date on the pediatric
cohort are insufficient to conclude on the value of using PTX3. The investigators
therefore wish to create a new paediatric cohort, in order to evaluate the PTX3 levels
for the paediatric population and also to perform the assay of a new marker, clusterin.
Clusterin (CLU) is an extracellular chaperone protein of constitutive expression. The
Innate Immunity team of the National Institute of Health and Medical Research (INSERM)
"1307-Scientific Research National Center (CNRS) 6075" unit has shown that Clu binds to
extracellular histones and inhibits their inflammatory, thrombotic and cytotoxic
properties. The investigators also observed (i) that in adults without severe sepsis
neutropenics, low serum levels of Clu at intake and lack of normalization of rates are
associated with higher mortality and (ii) Clu levels are inversely correlated with
circulating histone levels. All these data suggest that Clu would have a protective role
for histone-induced lesions during sepsis independently of antibiotic treatment, opening
an innovative therapeutic pathway in the management of severe sepsis.
CluPPFeN is based on the hypothesis that, in a pediatric population with episodes of
febrile aplasia, serum Clu and serum PTX3 levels would discriminate between febrile
episodes caused by bacterial infection and other etiologies and, As a result, would
reduce the consumption of antibiotics, which provide resistance, and the length of
hospitalization.
