Inclusion Criteria

Pediatric patients:

All pediatric subjects will be recruited from Intermountain Primary Children's Medical
Center (PCMC). At any point in time, there are 6-10 inpatients at PCMC who are being
treated as in-patients for febrile neutropenia. Each day, 2-3 new patients with febrile
neutropenia are admitted or transferred to PCMC from hospitals and clinics across the
intermountain area. Approximately 3-5 patients per week will be eligible for inclusion in
this study (having high-risk persistent febrile neutropenia without an obvious cause). The
target for this study is to recruit a minimum of 1-2 pediatric patients per month to the
protocol. Therefore, the eligible pediatric patient population should be more than
sufficient to meet this goal. Most of these patients are >10 years of age. The vast
majority are adolescents and teenagers, because pediatric patients at highest risk for
febrile neutropenia are those on high dose methotrexate for high risk leukemia and
lymphomas that target adolescents and teenagers. Leukemics constitute the largest
percentage of these patients. To be eligible for inclusion, subjects must be admitted for
treatment as in-patients for febrile neutropenia, with an absolute neutrophil count (ANC)
< 500 cells/mm3, in whom a fever persists without obvious source despite 5 days of broad
spectrum antibiotics. Typically, pediatric patients in this category will have been
treated with IV Fortaz (ceftazidime). We will also study patients that do not meet the
older definition of persistent (> 5 days) fever who for medical reasons an advanced
imaging study (typically CT scans) is now medically indicated for localization of a
possible site of infection. These patients will have a fever and be neutropenic, however
they may not have been febrile for > 5 days. Medical imaging is indicated sooner than the
typical 5 days due to the patients condition and need to localize a site of infection.

Exclusion criteria will include inability to undergo a FDG-PET/CT scan without conscious
sedation, medical instability that would preclude safe transport to the PET center in the
Huntsman Cancer Hospital (PCMC does not have a PET scanner), and a fasting serum glucose >
200 mg/dl. A negative pregnancy test will be required in post-menarche females prior to
inclusion.

Adult patients:

All adult subjects will be recruited from the Huntsman Cancer Hospital, patients will be
recruited from the general oncology service. As for the pediatric patients, those
considered eligible will include those with a documented fever > 5 days despite IV
antibiotics, an ANC < 500 cells/mm3, and in patient treatment as a high risk patient. We
will also study patients that do not meet the older definition of persistent (> 5 days)
fever who for medical reasons an advanced imaging study (typically CT scans) is now
medically indicated for localization of a possible site of infection. These patients will
have a fever and be neutropenic, however they may not have been febrile for > 5 days.
Medical imaging is indicated sooner than the typical 5 days due to the patients condition
and need to localize a site of infection. On average, 5-6 patients per week are admitted
to the Huntsman Cancer Hospital with the diagnosis of high risk persistent febrile
neutropenia. At any one time, there are typically 3-4 adult in patients on the ward with
the diagnosis of persistent febrile neutropenia. Of these, approximately 2-3 patients per
week will be eligible for inclusion in this study (having persistent febrile neutropenia
without an obvious cause). The target for this study is to recruit a minimum of 1-2 adult
patients per month to the protocol. Therefore, the eligible adult patient population
should be more than sufficient to meet this goal. As with the pediatric population, the
majority of these patients have leukemia and lymphoma (50:50). Adult patients may also
have multiple myeloma. In these patients, the typical duration of neutropenia is 3-4
weeks. Typically, the initial workup of the adult patients with febrile neutropenia is a
chest X-ray, CBC, urinalysis, peripheral and central line blood culture, and additional
studies only as directed by symptoms. Initial in-patient treatment for high risk patients
is typically with IV meropenem and ceftazidime. If fever persists beyond 5 days without
specific localizing signs or symptoms, antibacterials may be changed or added, and
antifungals are started (typically amphotericin B or caspofungin), typically persisting
until the white count returns to 1000 cell/mm3. Additional imaging studies are not done on
a consistent basis for the adults with persistent high-risk febrile neutropenia. Extended
imaging is typically done only as symptoms dictate. Typically, a source of infection is
found in only 40-50% of patients with febrile neutropenia at our institutions as well as
from the literature (Chaimberlain 2005; Hughes 2002; Roguin 1996). In the persistent
febrile neutropenia patient despite further and more comprehensive evaluation and
assessment a source is identified in only about an additional 10% of these patients.

As with pediatric patients, adult exclusion criteria will include inability to undergo a
FDG-PET/CT without conscious sedation, medical instability, a fasting serum glucose > 200
mg/dl, and pregnancy. A negative pregnancy test will be required of all females of
reproductive potential prior to inclusion.

Of note, patients from the bone marrow transplant unit will be eligible to participate in
this pilot study,. Many of these patients are placed on prophylactic antifungal agents at
the time of presentation of neutropenia and fever. This may cause a drug-induced fever in
a certain percentage of recipients. For this reason, the clinical picture is clouded
however the patients may still have an occult infection. Bone marrow transplant patients
will be included in the study as this is an exploratory study and the information gained
from assessing the ability of FDG-PET/CT to localize sites of infection in neutropenic,
febrile bone marrow transplant patients will be valuable.