Jessica Bate

Immunogenicity of Pandemic (H1N1) 2009 Vaccine in Children with Cancer in the United Kingdom

BACKGROUND Children with cancer have an increased susceptibility to influenza infection. The objective of this study was to assess the immunogenicity of pandemic (H1N1) 2009 vaccine in children with cancer. METHODS Children were recruited from the Royal Marsden Hospital, England, during November 2009. The vaccination schedule consisted of 2 doses of an AS03(B)-adjuvanted vaccine given at days 0 and 21. Serological analysis was performed on blood samples obtained at day 0 and day 42. The primary immunological end point was the seroconversion rate, which was defined as the proportion of subjects with an individual 4-fold increase in hemagglutination inhibition titer and a postvaccination hemagglutination inhibition titer ≥1:32. RESULTS Fifty-four children with a median age of 6.3 years (range, 1.4-16.6 years) were vaccinated and had samples taken for serological analysis. Twenty-four (44.4%) of 54 children demonstrated seroconversion. Seroconversion rates were 33.3% (9 of 27) among children with acute lymphoblastic leukemia, 36.4% (4 of 11) among those with lymphoma or other leukemias, 66.7% (6 of 9) among those with brain tumors, and 71.4% (5 of 7) among those with other solid tumors. Seroconversion occurred in 4 (28.6%) of 14 children receiving acute lymphoblastic leukemia maintenance therapy. Univariate analysis showed significantly higher responses among children with solid tumors, compared with those with hematological malignancies (11 [68.8%] of 16 vs 13 [34.2%] of 38; P = .03), and among those not receiving treatment, compared with those receiving treatment (7 [87.5%] of 8 vs 17 [37.0%] of 46; P = .02). Multivariable analysis showed that age, cancer type, and lymphopenia did not influence seroconversion rates. CONCLUSION These data suggest that this AS03(B)-adjuvanted pandemic (H1N1) 2009 vaccine can induce limited but useful protective immune responses in children with cancer.

Preventing varicella in children with malignancies: what is the evidence?

Purpose of review The prevention of varicella in children with cancer is generally agreed to be an important goal, because of their elevated risk of varicella zoster virus (VZV)-associated morbidity and mortality. However, there is a lack of consensus on the best means of achieving this. Here, we review the existing evidence in relation to postexposure prophylaxis against varicella in this group and summarize data regarding the role of active vaccination. Recent findings Death from varicella during treatment for cancer is now rare, but VZV disease and its prevention remain significant problems in paediatric oncology practice. Measures to reduce VZV exposure amongst seronegative individuals are often neglected. When exposure is known to have occurred, early administration of varicella zoster immune globulin (VZIG) is generally protective against severe and complicated varicella. However, many centres in the UK and Japan use an oral antiviral agent, aciclovir, in place of VZIG. Published evidence for the efficacy of aciclovir as postexposure prophylaxis (PEP) relates mostly to healthy children, with no controlled studies in the immunocompromised. Summary Good evidence already supports the administration of varicella vaccine to healthy susceptible family contacts of children with malignancy, but not to patients themselves. Further data are urgently needed to inform the choice of PEP against VZV in the immunocompromised.

Immunisation practices of paediatric oncology and shared care oncology consultants: A United Kingdom survey†

In March 2002, the Royal College of Paediatrics and Child Health (RCPCH) introduced guidelines for re‐immunisation of children after completion of standard‐dose chemotherapy and after haematopoietic stem cell transplant (HSCT).

Serotype-specific pneumococcal antibody concentrations in children treated for acute leukaemia

Children treated for acute leukaemia are at increased risk of infection with Streptococcus pneumoniae. The basis for this may include low levels of pneumococcal antibody but this has not been well studied. The authors measured serotype-specific pneumococcal IgG antibody concentrations in children treated for acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) ≥6 months after completion of standard-dose chemotherapy. Pneumococcal serotype-specific IgG antibody concentrations were low. None of the subjects had protective concentrations against all the heptavalent-pneumococcal conjugate vaccine serotypes. There was no significant difference in antibody concentrations between subjects with ALL and AML (p≥0.05). Children treated for ALL and AML generally have non-protective antibody concentrations against S pneumoniae. There is significant morbidity associated with pneumococcal disease in this patient group and strategies for vaccination are required.

A reaudit of current febrile neutropenia practice in UK paediatric oncology centres prior to implementation of NICE guidance

In September 2012, the National Institute for Clinical Excellence (NICE) published ‘Neutropenic sepsis: prevention and management of neutropenic sepsis in cancer patients’.1 No national guidelines for the management of neutropenic sepsis in children have been previously published. In 2008, the Childrens Cancer and Leukaemia Group produced a framework document for the treatment of febrile neutropenia (FN), based on a literature review and a Delphi survey.2 This document was designed to provide an evidence-based approach that could be used to inform local …

Neutropenic sepsis: prevention and management of neutropenic sepsis in cancer patients (NICE Clinical Guideline CG151)

Information about current guideline In September 2012, the National Institute for Clinical Excellence (NICE) published a guideline entitled ‘Neutropenic sepsis: prevention and management of neutropenic sepsis in cancer patients’.1 The aim of the guideline is to ‘improve outcomes by providing evidence-based recommendations on the prevention, identification and management of this life-threatening complication of cancer treatment’ for children, young people and adults. The National Collaborating Centre for Cancer was commissioned by NICE to develop the guideline and establish a Guideline Development Group, including children and young peoples cancer nurses and consultants, which reviewed the evidence and developed the recommendations. Previous guideline There are no previously published national guidelines for the management of neutropenic sepsis in children. In July 2008, the Childrens Cancer and Leukaemia Group (CCLG) produced a framework document for the treatment of febrile neutropenia, focusing on the definitions of fever and neutropenia, and on developing a practical management strategy for low-risk patients, which individual centres could incorporate into local policies. The document was produced in response to a survey suggesting wide variation in the definitions and management of febrile neutropenia, following an exhaustive literature review, small group discussion and a national Delphi consensus process.2 ,3 A recent audit of UK paediatric oncology centres revealed that current practice differs widely from recommendations contained within the CCLG framework.4 Box 2 ### Resources Controversial and key issues that the guideline addresses

Public and patient involvement in paediatric research

Public and patient involvement (PPI) in health research is a dynamic partnership between patients and/or members of the public and researchers. Involvement is distinct from being subjects of research (participation) as patients contribute to the research process as advisors and sometimes co-researchers. In practice, this may mean involvement in prioritising and developing research ideas, contributing to study design, carrying out the research and research dissemination.1 It should be emphasised that involvement is carried out ‘with’ or ‘by’ members of the public rather than ‘to’, ‘about’ or ‘for’ them.2 PPI offers researchers valuable and unique insight into the particular condition being investigated to make research more relevant to patients. PPI is needed to improve the quality of research and increase accountability. It is also reported to have benefits of increased recruitment and retention of study participants.3 The reasons for this are varied. The research questions are more likely to be aligned with outcomes valued by patients. Recruitment materials designed with the public will be written more suitably and with greater relevance. Importantly, the public bring important insight into how burdensome study requirements are to everyday life. Additionally, the idea of PPI is itself appealing, which increases willingness to participate in research. For todays researchers, active PPI has further relevance as funding bodies frequently require evidence of PPI in the development of a research proposal and ask how patients and the public might be involved in the conduct of the research. For patients, it is ethical for them to have a voice in research that may have an impact on their health. Dame Sally Davies, chief medical officer for England, advocates PPI as the rule rather than the exception:No matter how complicated the research, or how brilliant the researcher, patients and the public always offer unique, invaluable insights. …

Infection-related mortality in children with malignancy in England and Wales, 2003-2005

Infections are an important component of treatment‐related mortality in children with malignancy. Infection‐related mortality is potentially preventable and it is important to identify areas where prevention and treatment can be improved such as through vaccination, early diagnosis and aggressive management. The aim of this study is to describe the infections contributing to deaths in children under 15 years with malignancy in England and Wales in the period 2003–2005.

Varicella post-exposure prophylaxis in children with cancer: urgent need for a randomised controlled trial

We welcome the interest of Samuelson et al 1 in our work on prevention of varicella in children with cancer.2 However, they misrepresent our method for estimating the incidence of varicella zoster virus (VZV) exposure requiring post-exposure prophylaxis (PEP), which did not rely on consultant recollection. As described in detail in our paper, this was achieved by painstaking scrutiny of varicella zoster immunoglobulin …

Parental opinions on childhood varicella and the varicella vaccine: a UK multicentre qualitative interview study

Varicella-zoster virus can cause serious complications and require hospitalisation, even in healthy children.1 2 A live attenuated varicella vaccine was developed in the 1970s and is part of routine immunisation programmes in many countries including Japan, USA and Australia. The varicella vaccine has been shown to be immunogenic, safe and tolerable.3 However, this vaccine is not given routinely in the UK and is only recommended for certain high-risk groups. The aim of this study was to explore parental experiences and perceptions of childhood varicella …