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ICNA President-Elect elections are underway. The online voting site will remain open until 12 Noon GMT on Tuesday April 17, 2012. Your vote in this election is very important. Please take a few minutes to visit the online voting site and register your choice. If you haven't received your voting credentials by email, please contact This email address is being protected from spambots. You need JavaScript enabled to view it. asap
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Immunotherapy with peptide vaccines may offer a much-needed therapeutic option for gliomas in children, which carry a poor prognosis despite current treatments.
In a pilot trial of subcutaneous vaccinations with peptides for glioma-associated antigen (GAA) epitopes in children who have been newly diagnosed with brain stem gliomas, cerebral high-grade gliomas, or recurrent gliomas, the immunotherapy was well tolerated and demonstrated immunologic and clinical activity, Dr. Ian F. Pollack reported April 2 at the annual meeting of the American Association for Cancer Research.
For the pilot study Dr. Pollack, chief of pediatric neurosurgery at Children’s Hospital of Pittsburgh Brain Care Institute, and his colleagues have enrolled 27 human leukocyte antigen (HLA) A2–positive children to date, including 16 who are newly diagnosed with brain stem gliomas, 5 with newly diagnosed high-grade gliomas, and 6 with recurrent gliomas. The GAAs were EphA2, interleukin-13 receptor alpha 2 (IL-13RA2), and survivin, he said.
All of the children received eight courses of subcutaneous vaccinations with peptides for GAA epitopes emulsified in Montanide-ISA-51 every 3 weeks, along with intramuscular injections of the immunoadjuvant poly-ICLC, which promotes the infiltration of effector T cells into intracranial gliomas.
“Our primary end points were safety and T-cell response against vaccine-targeted [GAAs],” he said, noting that treatment response was assessed clinically and by MRI.
The preliminary results reported at the meeting are based on an interim analysis of 22 evaluable patients. To date, no non–central nervous system toxicities have limited the vaccine dosages, Dr. Pollack said. Of the 22 children, 4 showed signs of rapidly progressive disease, 14 had stable disease for more than 3 months, 3 had sustained partial responses, and 1 had prolonged disease-free status after surgery, he reported.
Symptomatic “pseudoprogression” – consisting of transient neurologic deterioration and tumor enlargement, followed by tumor regression and stabilization on decreasing steroid doses with sustained partial response – was observed in four of the children with brain stem glioma, said Dr. Pollack, who is also codirector of the University of Pittsburgh Cancer Institute’s brain tumor program.
Results of the ELISPOT (enzyme-linked immunosorbent spot) assay, which was completed in seven of the children, showed responses in six of them. Specifically, the investigators observed responses to IL-13RA2 in five cases, EphA2 in three cases, and survivin in three cases, Dr. Pollack said.
“Based on what we’ve seen so far, it seems that these kids are able to mount immune responses to the vaccine at high rates, possibly higher than we’ve seen in adult studies,” likely because of their robust immune systems, he said in an interview.
The observation of immunologic and clinical response – particularly the evidence of tumor shrinkage in children with very high-risk tumors – “has been extremely encouraging and somewhat surprising,” Dr. Pollack reported. “This is the first study of its type that examined peptide vaccine therapy for children with brain tumors like this.”
The findings are especially notable because children with these tumors generally do not respond well to standard chemotherapy, he said, stressing that if further study validates the early findings, “immunotherapy may be a promising strategy to control tumor growth.”
The study was funded by the National Institutes of Health. Dr. Pollack disclosed having no potential conflicts of interest.
Source: Elsevier Medical News
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Vaccines for measles were not associated with an increased risk of febrile seizures* among 4-6 year olds during the six weeks after vaccination, according to a study by the Kaiser Permanente Vaccine Study Center that appears in the current issue of Pediatrics.
Funded by the U.S. Centers for Disease Control, the study of 86,750 children follows an earlier study published in Pediatrics that showed one particular combination of measles-containing vaccine - the measles, mumps, rubella and chickenpox containing vaccination (or MMRV) - was associated with an increased risk of febrile seizures in 1-to-2-year-old children, compared with same-day administration of the separate vaccine for MMR (measles, mumps, rubella) and the V (varicella) vaccine for chicken pox. This new study sought to evaluate, for the first time, the risk of febrile seizures following MMRV or separate MMR plus V vaccines among 4-6 year olds and found no increased risk of febrile seizures.
In the United States, children receive two doses of measles, mumps,rubella and varicella vaccines - the first between 1-2 years and the second between ages 4-6. Among 1-2 year olds, the risk of febrile seizures 7-10 days after MMRV was double that of separate MMR+V. For children aged 4-6 receiving their second dose, no such association was found with either measles vaccine combination, according to Kaiser Permanente researchers.
This study of 4-6 year olds analyzed 86,750 children aged 48-83 months old from seven participating Vaccine Safety Datalink sites between January 2000 and October 2008 who received either MMRV; separately administered, same-day MMR plus varicella; or MMR or varicella vaccines alone. The results provide reassuring evidence that neither MMRV, nor MMR plus V, appear to be associated with an increased risk of post-vaccination febrile seizures in this 4-6 age group.
This study builds on the work of a previous study published in Pediatrics in June 2010 that showed that the combination vaccine for measles, mumps, rubella and chickenpox (MMRV) is associated with double the risk of febrile seizures for 1-to-2 year-olds compared with same-day administration of the separate vaccine for measles, mumps, rubella (MMR) and the varicella (V) vaccine for chicken pox.
The Vaccine Safety Datalink project is a collaborative effort among CDC's Immunization Safety Office and eight managed care organizations: Kaiser Permanente Northern California, Kaiser Permanente Southern California, Kaiser Permanente Colorado, Kaiser Permanente Northwest, Health Partners (Minn.), Group Health Cooperative (Wash.), Marshfield Clinic (Wisc.) and Harvard Pilgrim Health Care (Mass.). The VSD project was established in 1990 to monitor immunization safety and address the gaps in scientific knowledge about rare and serious events following immunization. The VSD shares electronic health records from the organizations' health systems.
MMRV was licensed by the FDA in 2005 and subsequently recommended by the Advisory Committee on Immunization Practices in 2006. Although pre-licensure studies of MMRV among 1-2 year olds noted higher rates of fever and measles-like rash one to two weeks post vaccination when compared with separate MMR+V, it was unknown at the time of MMRV's licensure whether a higher rate of fevers was similarly associated with increased risk of febrile seizures. In February 2008, Kaiser Permanente researchers alerted the CDC's Advisory Committee on Immunization Practices to preliminary evidence of an increased risk of febrile seizures following MMRV for 1-2 year olds, findings which were subsequently confirmed in the 2010 study published in Pediatrics.
The Vaccine Safety Datalink - which we used to conduct both the study of 1-2 year olds and the study of 4-6 year olds, is a premier example of how different managed care organizations can leverage their electronic medical records to improve vaccine safety and monitoring.
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