BATs in the hematology belfry Moorehead, Paul C.
Haemophilia : the official journal of the World Federation of Hemophilia,
March 2023, 2023-03-00, 20230301, Letnik:
29, Številka:
2
Journal Article
With significant improvements in the survival rates for most childhood cancers, there is increased pressure to determine how follow-up or aftercare for survivors is best structured.
Previous work in ...this area has not been consistent in how it categorizes models of aftercare, which risks confusion between studies and evaluations of different models. The adoption of a standardized method for classifying and describing different models of aftercare is necessary in order to maximize the applicability of the available evidence. We identify some of the different ways models of aftercare have been classified in previous research. We then propose a revised taxonomy which allows for a more consistent classification and description of these models. The proposed model bases the classification of models of aftercare on who is the lead provider, and then collects data on five other key features: which other providers are involved in providing aftercare, where care is provided, how are survivors engaged, which services are provided, and who receives aftercare.
There is a good deal of interest in the effectiveness of different models of aftercare. Future research in this area would be assisted by the adoption of a shared taxonomy that will allow programs to be identified by their structural type.
We report a newborn with hemolytic disease of the fetus and newborn (HDFN) with rapid resolution of extreme hyperferritinemia without chelation. An infant born at 35+3 weeks with HDFN and a history ...of 3 intrauterine transfusions developed severe hyperferritinemia (maximum, 8258 mcg/L) without evidence of toxic iron deposition on liver biopsy. Her hyperferritinemia was managed with observation alone, and ferritin levels normalized rapidly. This case supports observation as being the preferred alternative to chelation therapy for significant hyperferritinemia in newborns with HDFN in the absence of demonstrated toxic end-organ iron deposition. We also include a review of the related available literature.
Venous thromboembolism (VTE) is a well-recognized complication in pediatric oncology patients. Studies in adult oncology patients have suggested a potential negative association between VTE and ...survival, but this association has not been examined in pediatric patients yet. The aim of this study was to assess the association of VTE with survival in pediatric oncology patients. Data from all pediatric oncology patients treated at the two tertiary care centers in Atlantic Canada were pooled to create a population-based cohort. The association between VTE and survival was analyzed using a Cox proportional hazards model stratified by diagnosis group (leukemia, lymphoma, and other; sarcoma) and adjusted for age at diagnosis and sex. Out of 939 patients included in this study, 73 had a VTE (8%) and 131 (14%) patients died during the study period. Children in the leukemia/lymphoma/other group with a VTE had significantly poorer survival relative to children in the same group who did not have a VTE. Although children with sarcoma and VTE had poorer survival compared to children with sarcoma with no VTE, this association was not statistically significant. In this population-based study, we found a negative association between VTE and survival in pediatric oncology patients. If future studies confirm this association, this finding may have prognostic implications and potentially offer new avenues for the management of pediatric patients with cancer.
Inflammatory signals such as pathogen- and danger-associated molecular patterns have been hypothesized as risk factors for the initiation of the anti–factor VIII (FVIII) immune response seen in 25% ...to 30% of patients with severe hemophilia A (HA). In these young patients, vaccines may be coincidentally administered in close proximity with initial exposure to FVIII, thereby providing a source of such stimuli. Here, we investigated the effects of 3 vaccines commonly used in pediatric patients on FVIII immunogenicity in a humanized HA murine model with variable tolerance to recombinant human FVIII (rhFVIII). Mice vaccinated intramuscularly against the influenza vaccine prior to multiple infusions of rhFVIII exhibited a decreased incidence of rhFVIII-specific neutralizing and nonneutralizing antibodies. Similar findings were observed with the addition of an adjuvant. Upon exposure to media from influenza- or FVIII-stimulated lymph node or splenic lymphocytes, naïve CD4+ lymphocytes preferentially migrated toward media from influenza-stimulated cells, indicating that antigen competition, by means of lymphocyte recruitment to the immunization site, is a potential mechanism for the observed decrease in FVIII immunogenicity. We also observed no differences in incidence or titer of rhFVIII-specific antibodies and inhibitors in mice exposed to the live-attenuated measles-mumps-rubella vaccine regardless of route of administration. Together, our results suggest that concomitant FVIII exposure and vaccination against influenza does not increase the risk of inhibitor formation and may in fact decrease anti-FVIII immune responses.
•Vaccination against influenza, with and without the adjuvant MF59, decreases the risk of inhibitor development in HA mice.•Decreased FVIII immunogenicity may be attributed to antigenic competition via T-cell chemotaxis toward the site of vaccination.
The development of inhibitory antibodies to factor VIII is the most serious complication of replacement therapy in hemophilia A. Activation of the innate immune system during exposure to this protein ...contributes to inhibitor development. However, avoidance of factor VIII exposure during innate immune system activation by external stimuli (e.g., vaccines) has not been consistently shown to prevent inhibitors. We hypothesized that dexamethasone, a drug with potent anti-inflammatory effects, could prevent inhibitors by promoting immunologic tolerance to factor VIII in hemophilia A mice. Transient dexamethasone treatment during ainitial factor VIII exposure reduced the incidence of anti-factor VIII immunoglobulin G in both a conventional hemophilia A mouse model (E16KO, 77%
100%,
=0.048) and a hemophilia A mouse model with a humanized major histocompatibility complex type II transgene (E17KO/hMHC, 6%
33%,
=0.0048). More importantly, among E17KO/hMHC mice that did not develop anti-factor VIII immunoglobulin G after initial exposure, dexamethasone-treated mice were less likely to develop a response after re-exposure six (7%
52%,
=0.005) and 16 weeks later (7%
50%,
=0.097). Similar results were obtained even when factor VIII re-exposure occurred in the context of lipopolysaccharide (30%
100%,
=0.069). The ability of these mice to develop immunoglobulin G to human von Willebrand factor, a structurally unrelated antigen, remained unaffected by treatment. Transient dexamethasone administration therefore promotes antigen-specific immunologic tolerance to factor VIII. This effect is associated with an increase in the percentage of thymic regulatory T cells (12.06%
4.73%,
<0.001) and changes in the thymic messenger ribonucleic acid transcription profile.
Pediatric B-acute lymphoblastic leukemia (B-ALL) is a disease of abnormally growing B lymphoblasts. Here we hypothesized that extracellular vesicles (EVs), which are nanosized particles released by ...all cells (including cancer cells), could be used to monitor B-ALL severity and progression by sampling plasma instead of bone marrow. EVs are especially attractive as they are present throughout the circulation regardless of the location of the originating cell. First, we used nanoparticle tracking analysis to compare EVs between non-cancer donor (NCD) and B-ALL blood plasma; we found that B-ALL plasma contains more EVs than NCD plasma. We then isolated EVs from NCD and pediatric B-ALL peripheral blood plasma using a synthetic peptide-based isolation technique (Vn96), which is clinically amenable and isolates a broad spectrum of EVs. RNA-seq analysis of small RNAs contained within the isolated EVs revealed a signature of differentially packaged and exclusively packaged RNAs that distinguish NCD from B-ALL. The plasma EVs contain a heterogenous mixture of miRNAs and fragments of long non-coding RNA (lncRNA) and messenger RNA (mRNA). Transcripts packaged in B-ALL EVs include those involved in negative cell cycle regulation, potentially suggesting that B-ALL cells may use EVs to discard gene sequences that control growth. In contrast, NCD EVs carry sequences representative of multiple organs, including brain, muscle, and epithelial cells. This signature could potentially be used to monitor B-ALL disease burden in pediatric B-ALL patients
via
blood draws instead of invasive bone marrow aspirates.
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