Vaccinations in children with hematologic malignancies and those receiving hematopoietic stem cell transplants or cellular therapies.

Children who are immune compromised are uniquely threatened by a higher risk of infections, including vaccine-preventable diseases (VPDs). Children who undergo chemotherapy or cellular therapies may not have preexisting immunity to VPDs at the time of their treatment including not yet receiving their primary vaccine series, and additionally they have higher risk of exposures (e.g., due to family structures, daycare and school setting) with decreased capacity to protect themselves using nonpharmaceutic measures (e.g., masking). In the past, efforts to revaccinate these children have often been delayed or incomplete. Treatment with chemotherapy, stem cell transplants, and/or cellular therapies impair the ability of the immune system to mount a robust vaccine response. Ideally, protection would be provided as soon as both safe and effective, which will vary by vaccine type (e.g., replicating versus nonreplicating; conjugated versus polysaccharide). While a single approach revaccination schedule following these therapies would be convenient for providers, it would not account for patient specific factors that influence the timing of immune reconstitution (IR). Evidence suggests that many of these children would mount a meaningful vaccine response as early as 3 months following completion of treatment. Here within, we provide updated guidance on how to approach vaccination both during and following completion of these therapies.

Pott's Puffy Tumor in an Inflammatory Bowel Disease Patient on Anti-TNF Therapy.

BACKGROUND Anti-TNF-alpha therapies were the first class of biologics to be used in treatment of moderate to severe IBD. Immunosuppression status that develops from using anti-TNF-a therapies increases the risk of serious and opportunistic infections. We present here a rare case of serious infection that developed in an IBD patient while on anti-TNF therapy. CASE REPORT Our patient was a 14-year-old boy with a history of chronic sinusitis and ulcerative colitis who had been on infliximab therapy for the last 3 years. He presented with facial swelling and worsening constant frontal headache. Imaging showed frontal scalp subgaleal abscess, mild frontal calvarial early osteomyelitis, bilateral preseptal cellulitis, and acute and chronic paranasal sinus disease. He was treated with intravenous antibiotics and underwent sinus surgery with incision and drainage of the forehead abscess. He recovered well and resumed his infliximab infusions 3 weeks after the surgery. CONCLUSIONS PPT is a serious complication of untreated sinusitis. IBD patients on biologics can have higher risk of developing such complications because of their decreased ability to fight infections. Although the risk of serious infections declines significantly after the first year of using biologics, physicians should keep a low threshold for investigating symptomatic patients for serious infections, as they require prompt intervention. Despite the potential complications from using biologics, the benefits of this therapy in IBD patients outweigh the risks.

A Pediatric Infectious Diseases Perspective of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Novel Coronavirus Disease 2019 (COVID-19) in Children.

Understanding the role that children play in the clinical burden and propagation of severe acute respiratory syndrome coronavirus 2, responsible for coronavirus disease 2019 (COVID-19) infections, is emerging. While the severe manifestations and acute clinical burden of COVID-19 have largely spared children compared with adults, understanding the epidemiology, clinical presentation, diagnostics, management, and prevention opportunities and the social and behavioral impacts on child health is vital. Foremost is clarifying the contribution of asymptomatic and mild infections to transmission within the household and community and the clinical and epidemiologic significance of uncommon severe post-infectious complications. Here, we summarize the current knowledge, identify resources, and outline research opportunities. Pediatric infectious diseases clinicians have a unique opportunity to advocate for the inclusion of children in epidemiological, clinical, treatment, and prevention studies to optimize their care as well as to represent children in the development of guidance and policy during pandemic response.

Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host.

The accumulation of myeloid suppressor cells (MSCs) is associated with immune suppression in tumor-bearing mice and in cancer patients. The suppressive activity of MSC correlates with the expression of the myeloid markers Gr-1, CD115 (macrophage colony-stimulating factor receptor), and F4/80. Gr-1(+)CD115(+) MSCs, in addition to being able to suppress T-cell proliferation in vitro, can induce the development of Foxp3(+) T regulatory cells (Treg) in vivo, which are anergic and suppressive. Furthermore, the secretion of interleukin (IL)-10 and transforming growth factor-beta by Gr-1(+)CD115(+) MSCs was induced and enhanced, respectively, on IFN-gamma stimulation. The development of Treg requires antigen-associated activation of tumor-specific T cells, depends on the presence of IFN-gamma and IL-10, and is independent of the nitric oxide-mediated suppressive mechanism by MSC. Our data provide evidence that Gr-1(+)CD115(+) MSC can mediate the development of Treg in tumor-bearing mice and show a novel immune suppressive mechanism by which MSCs can suppress antitumor responses.

NK and CD8+ T cell-mediated eradication of poorly immunogenic B16-F10 melanoma by the combined action of IL-12 gene therapy and 4-1BB costimulation.

In previous reports, systemic administration of a stimulatory monoclonal antibody directed against the 4-1BB receptor had no effect on survival or tumor burden in mice inoculated with the poorly immunogenic B16-F10 melanoma. We combined IL-12 gene transfer with 4-1BB costimulation to explore a previously noted cooperative anti-tumor effect against this model tumor. We hypothesize that the innate immune response mediated by IL-12-activated natural killer (NK) cells initiates the activation of the immune system, leading to the priming of T cells, whereas 4-1BB costimulation enhances the function of primed tumor-specific T cells. The effect of the combination therapy on the growth of subcutaneous (s.c.) tumors and pulmonary metastasis was examined. The combination therapy significantly retarded the growth of subcutaneously-inoculated tumors, and 50% of tumor-bearing mice survived with complete tumor regression. In contrast, neither IL-12 gene transfer nor anti-4-1BB antibody administration alone was as effective. Enhanced CTL activity against both B16-F10 tumor cells and TRP-2-pulsed EL4 syngeneic tumor cells was observed in tumor-bearing animals treated with the combination therapy 2 weeks after treatment and, in long-term survivors from this combination therapy, at >120 days. In a pulmonary metastatic model, only the combination therapy generated significant protection against metastasis. In vivo depletion of NK or CD8(+) but not CD4(+) subsets eliminated the protective immunity. Furthermore, NK cell depletion significantly reduced both tumor-specific CTL activity and the number of tumor-specific IFN-gamma-producing cells, suggesting that this synergistic effect requires the participation of both NK and CD8(+) T cells.