Annual Meeting Proceedings Part 1 - American Society of Clinical ...

9552 General Poster Session (Board #40G), Sun, 8:00 AM-12:00 PM
Contribution of diet and physical activity to metabolic parameters among
survivors of childhood leukemia. Presenting Author: Emily S. Tonorezos,
Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Survivors of childhood acute lymphoblastic leukemia (ALL) are
at increased risk for obesity, insulin resistance and increased visceral
adiposity. A history of cranial radiation therapy (CRT) worsens this risk. In
non-cancer populations, adherence to a Mediterranean Diet has been
shown to improve metabolic parameters and risk of diabetes mellitus.
Whether diet may contribute to insulin resistance and increased adiposity
in ALL survivors is not known. Methods: We surveyed 117 adult survivors of
childhood ALL using the Harvard Food Frequency Questionnaire. Physical
activity energy expenditure (PAEE) was measured with the SenseWear Pro2
Armband. Fasting blood was obtained on all subjects and insulin resistance
was estimated using the Homeostasis Model for Insulin Resistance (HOMA-
IR). Visceral adiposity was measured by abdominal CT. Adherence to a
Mediterranean Diet pattern was calculated using the index developed by
Trichopoulou. Subjects were compared using univariate analysis. Results:
Subjects were majority female (56%); 25% were minority or Hispanic
white. A history of CRT was present in 15 (29%) men and 25 (38%)
women. Among all subjects, greater adherence to a Mediterranean diet
pattern was associated with improved HOMA-IR (p�0.14), visceral adiposity
(p�0.03), subcutaneous adiposity (p�0.005), waist circumference
(p�0.02), and body mass index (p�0.03) (all unadjusted analyses). The
effect of adherence to a Mediterranean diet on insulin resistance was
especially notable in men who did not receive CRT (p�0.06). Higher dairy
intake was found to worsen HOMA-IR (p�0.014), but other individual
components of the Mediterranean diet, such as low intake of meat and high
intake of fruits and vegetables, were not significant. Inclusion of PAEE did
not alter our findings, although higher PAEE was associated with lower body
mass index. Conclusions: Adherence to a Mediterranean diet pattern,
especially low consumption of dairy products, may improve insulin resistance
in survivors of childhood ALL. Further study is warranted.
9554 General Poster Session (Board #41A), Sun, 8:00 AM-12:00 PM
Minimal residual disease by flow cytometry at the end of chemotherapy for
remission induction in pediatric patients with acute lymphoblastic leukemia:
Experience from a center in a low-income country. Presenting Author:
Eloy Perez, Hospital Infantil de Morelia Eva Samano de Lopez Mateos,
Morelia, Mexico
Background: The presence of minimal residual disease (MDR) following
therapy for acute lymphoblastic leukemia (ALL) has been shown to be an
important prognostic marker in many studies. MRD is typically detected
either by polymerase chain reaction amplification or by flow cytometry.
Flow-based MRD assessment has the potential for rapidly identifying
patients at increased risk of relapsed, allowing for prompt changes in
therapy, including earlier intensification. There are not many information
about the response by MRD in countries with limited resources. Methods:
The patients included were 90 ALL patients treated at the Hospital Infantil
de Morelia from June 1, 2009 to January 5, 2012. MRD positivity (�) was
defined as �0.01% of the gated population. Results: MRD was obtained in
90 patients, 38 males and 36 females. The median age was 7 years (10
months to 15 years). The levels of MRD were: �0.01, 74 (82.2%),
0.01-1%, 9 (10%), �1%, 7 (7.7%). There was not a statistically
significant association between the most important ALL prognostic factors
(Gender, Age at diagnosis, White blood cell count at diagnosis, Central
Nervous System disease, Prednisone response, DNA Index, Immunophenotype).
Conclusions: The good response found is similar to that reported by
international groups, a situation which suggests that the response to
chemotherapy is appropriate. However, cure rates are still not equal making
it necessary to review institutional treatment protocols and social characteristics
of the population to achieve cure rates reported by international
groups.
Pediatric Oncology
619s
9553 General Poster Session (Board #40H), Sun, 8:00 AM-12:00 PM
Fever at diagnosis of pediatric acute lymphoblastic leukemia (ALL): Are
antibiotics really necessary? Presenting Author: Monica Khurana, Children’s
Hospital Oakland Research Institute, Oakland, CA
Background: Great variability exists in the management of suspected
bacteremia in febrile, neutropenic pediatric ALL patients during chemotherapy.
The National Comprehensive Cancer Network and Infectious
Diseases Society of America encourage immediate, empiric antibiotics in
patients with chemotherapy-induced fever and neutropenia to reduce
infection-related mortality. No standard recommendation exists for patients
with isolated fever at initial presentation of their ALL. This study
evaluates bacteremic episodes in this subpopulation of pediatric patients.
Methods: We retrospectively analyzed 245 consecutive patients with ALL at
Children’s Hospital Oakland from 2000 through 2011. Using electronic
medical records, we investigated each patient’s history and outcome. We
surveyed bacteremic episodes up to 60 days after presentation per National
Healthcare Safety Network’s guidelines. Inclusion criteria were patients
with fever at presentation, which prompts a blood culture, and were started
on antibiotics. We stratified bacteremic episodes into community-acquired
(up to three days from admission) and nosocomial (four to 60 days).
Results: Seventy-seven patients met the inclusion criteria, five of whom had
positive cultures – four were contaminants (three coagulase-negative
Staphylococcus and one non-anthracis Bacillus) and one was a true
nosocomial bactermic episode (E coli). There were no infection-related
deaths in the first 60 days of diagnosis in this cohort. Conclusions: Given
our institution’s rarity of bacteremic episodes, we contemplate a more
judicious use of antibiotics, including quicker narrowing of broad-spectrum
antibiotics coverage and discontinuing all antibiotics sooner. These modifications
may decrease bacterial resistance to antibiotics, reduce costs, and
shorten patients’ hospitalization. We encourage other institutions to
conduct a similar investigation.
9555 General Poster Session (Board #41B), Sun, 8:00 AM-12:00 PM
YM155 sensitivity in pediatric acute lymphoblastic leukemia. Presenting
Author: Bill H. Chang, Doernbecher Children’s Hospital, Portland, OR
Background: Despite advances in treatment and outcomes in pediatric
acute lymphoblastic leukemia, there continue to be subsets of patients that
are refractory to standard intensive chemotherapy. Therefore, novel agents
are needed to further advance treatment for this disease. YM155 (Astellas)
is a selective suppressant of survivin expression. Survivin has been shown
to be over-expressed in malignant cells and in relapsed ALL. Early adult
phase I/II studies show promise in both tolerability and possible efficacy in
B-cell malignancies. Methods: Fresh diagnostic leukemic patient samples,
ALL cell lines, and xenograft samples were obtained and subjected to
YM155 at doses ranging from 1nM to 10�M. Samples were then tested for
viability using standard methane-thiosulfate, apoptosis using Guava nexin
Annexin V binding, protein expression using immunoblot, and P53 activation
with phospho-flow cytometry. Results: The median IC50 for viability and
apoptosis for the samples are: NCI standard risk ALL 5.3nM �3.47, NCI
high risk ALL 91.76 nM �93.42, T-ALL 336.6nM �147.7, AML 333.6nM
�489, Ph�ALL xenografts 3.8nM �1.04, and ALL cell lines 18.5nM
�135. Ph�ALL samples, including primary patient, xenograft, and dasatinib
(BMS) resistant samples remain significantly sensitive to YM155. For
dasatinib sensitive samples, combination therapy suggests an additive
effect by isobologram analysis. Immunoblot and RT2-PCR Arrays (Qiagen)
identify that multiple protein expression are decreased with YM155
treatment. Conclusions: Our data supports the model of the use of YM155
as a treatment for ALL including an added benefit in combination with
dasatinib in Ph�ALL. Although initial studies suggested that YM155 is a
selective suppressant of survivin, subsequent studies are beginning to
identify off target effects. These off target effects may enhance the drugs
potential for activating cell death. Finally, we show that screening primary
samples with YM155 has the potential to select a target population that is
more sensitive to YM155 treatment. Future studies will be designed to
develop YM155 as an additional therapeutic agent for pediatric acute
lymphoblastic leukemia.
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