Evaluating a Transition Workbook for Childhood Cancer Survivors: a Pilot Study.

Many childhood cancer survivors (CCS) could benefit from improved knowledge about their cancer diagnosis, the treatments received, and associated risks during the period when they transition into adult aftercare. Interventions that support the transition from pediatric to adult care have showed high patient satisfaction. We developed an educational workbook, "Life After the Janeway," to support CCS transition into adult care. We evaluated its understandability, actionability, and overall acceptability, using an online survey based on the Agency for Healthcare Research and Quality's Patient Education Materials Assessment Tool for Printable Material (PEMAT-P). Ten participants completed the survey. The overall PEMAT-P score was 94.06 (SD ± 7.40). Mean scores for understandability and actionability were 92.83 (SD ± 8.79) and 98.15 (SD ± 5.24) respectively. Interrater reliability found strong agreement across survey items. Participants support efforts to improve transition and felt positive about the intervention. The workbook was shown to be understandable and actionable to likely users. The next steps will focus on delivering the workbook to CCS going through their transition of care and exploring developing the workbook in an electronic format.

Residual meta-iodobenzyl guanidine (MIBG) positivity following therapy for metastatic neuroblastoma: Patient characteristics, imaging, and outcome.

BACKGROUND: Meta-iodobenzylguanidine(MIBG) scans are used to detect neuroblastoma metastatic lesions at diagnosis and during posttreatment surveillance. MIBG positivity following induction chemotherapy correlates with poor outcome; however, there are reports of patients with progression-free survival despite MIBG positivity at the end of therapy. The factors distinguishing these survivors from patients who progress or relapse are unclear. FDG-positron-emission tomography (PET) scans can also detect metastatic lesions at diagnosis; however, their role in posttherapy surveillance is less well studied. METHODS: We performed a retrospective analysis of International Neuroblastoma Staging System (INSS) stage 4 patients to identify those with residual MIBG-avid metastatic lesions on end-of-therapy scans without prior progression. Data collected included age, disease sites, histopathology, biomarkers, treatment, imaging studies, and response. RESULTS: Eleven of 265 patients met inclusion criteria. At diagnosis three of 11 patients were classified as intermediate and eight of 11 high risk; nine of 11 had documented marrow involvement. Histologic classification was favorable for four of 10 and MYCN amplification was detected in zero of 11 cases. The median time with persistent MIBG positivity following treatment was 1.5 years. Seven patients had at least one PET scan with low or background activity. Biopsies of three of three MIBG-avid residual lesions showed differentiation. All patients remain alive with no disease progression at a median of 4.0 years since end of therapy. CONCLUSION: Persistently MIBG-avid metastatic lesions in subsets of patients following completion of therapy may not represent active disease that will progress. Further studies are needed to determine whether MYCN status or other biomarkers, and/or PET scans, may help identify patients with residual inactive MIBG lesions who require no further therapy.

Conservative Management of Hyperferritinemia in Hemolytic Disease of the Fetus and Newborn: A Case Report and Review of the Literature.

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.

Pediatric CNS Tumor Patients Have Significantly Lower Requirement of Tissue Plasminogen Activator for Episodes of Central Venous Catheter Dysfunction Compared With Other Pediatric Oncology Patients: Results of a Population-based Cohort Study.

PURPOSE: Central venous catheters (CVCs) are an important component of care delivery in pediatric oncology patients. However, CVC dysfunction is a common problem. Tissue plasminogen activator (tPA) is often administered to re-establish function, however, specific experience in pediatric patients with central nervous system (CNS) tumors is lacking. The goal of this study was to investigate the CVC experience and use of tPA for episodes of CVC dysfunction in pediatric patients with CNS tumors in comparison with other patients. METHODS: Medical records of all pediatric oncology patients from the 4 Atlantic provinces in Canada (Nova Scotia, New Brunswick, Prince Edward Island, and Newfoundland and Labrador) were reviewed. Data collected included demographics, treatment, details of CVCs along with CVC dysfunction, and tPA use. RESULTS: The cohort consisted of 1152 pediatric oncology patients, 222 (19.3%) of whom had CNS tumors. CVC dysfunction requiring tPA administration occurred in 12 (5.4%) of patients with CNS tumors compared with 182 (19.6%) of patients with non-CNS tumors (P=0.0001). Multivariate logistic regression analysis showed that administration of tPA for CVC dysfunction was 2.5 times more likely in patients with non-CNS tumors than those with CNS tumors (P=0.012; 95% confidence interval, 1.3-4.9). CONCLUSIONS: Our study showed that pediatric patients with CNS tumors require significantly less frequent administration of tPA for episodes of CVC dysfunction than patients with non-CNS tumors after adjusting for confounding factors. Hypotheses for this include: potential biologic differences of tumors, the role of the blood-brain barrier, or systematic differences in intensity of treatments.

Standardizing the categorizations of models of aftercare for survivors of childhood cancer.

BACKGROUND: 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. MAIN BODY: 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. CONCLUSION: 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.

Concurrent influenza vaccination reduces anti-FVIII antibody responses in murine hemophilia A.

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.

Dexamethasone promotes durable factor VIII-specific tolerance in hemophilia A mice via thymic mechanisms.

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% vs 100%, P=0.048) and a hemophilia A mouse model with a humanized major histocompatibility complex type II transgene (E17KO/hMHC, 6% vs 33%, P=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% vs 52%, P=0.005) and 16 weeks later (7% vs 50%, P=0.097). Similar results were obtained even when factor VIII re-exposure occurred in the context of lipopolysaccharide (30% vs 100%, P=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% vs 4.73%, P<0.001) and changes in the thymic messenger ribonucleic acid transcription profile.

Correction to: The association of venous thromboembolism with survival in pediatric cancer patients: a population-based cohort study.

The Figure 1 used in the originally published version of this article was incorrect.

The association of venous thromboembolism with survival in pediatric cancer patients: a population-based cohort study.

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.

Generation and optimization of the self-administered pediatric bleeding questionnaire and its validation as a screening tool for von Willebrand disease.

OBJECTIVE: Our objective was to generate, optimize, and validate a self-administered pediatric bleeding questionnaire (Self-PBQ) as a screening tool for von Willebrand disease (VWD) in children referred to the hematology clinic for the first time. STUDY DESIGN: The Self-PBQ was generated by combining the validated expert-administered PBQ and the International Society on Thrombosis and Hemostasis (ISTH) bleeding assessment tool (BAT). Medical terminology was translated into lay language requiring a grade 4 reading level. In Phase 1, the Self-PBQ was optimized and the level of agreement between the Self-PBQ and the expert-administered PBQ was determined. Phase 2 established the normal range of bleeding scores (BSs) of the Self-PBQ. Phase 3 examined the Self-PBQ as a screening tool for first-time referrals to the hematology clinic. RESULTS: The Self-PBQ is a reliable surrogate for the expert-administered PBQ with an excellent intraclass correlation (ICC) of 0.917. The Self-PBQ was scored with the PBQ and the ISTH-BAT scoring systems, for which its normal BS ranges are -1 to 2 or 0 to 2, respectively. A positive Self-PBQ BS (≥3) had a sensitivity of 78%, a specificity of 37%, a positive predictive value of 0.18, and a negative predictive value of 0.91 for identifying VWD in children being investigated by a hematologist for a bleeding disorder. CONCLUSION: The Self-PBQ generates comparable BSs to the expert-administered PBQ and is a reliable, reasonably sensitive screening tool to incorporate into the assessment of children presenting to a hematologist for the investigation of an inherited bleeding disorder.

A Prospective Study of the Association Between Clinically Significant Bleeding in PICU Patients and Thrombocytopenia or Prolonged Coagulation Times.

OBJECTIVE: There are no proven methods to predict the risk of clinically significant bleeding in the PICU. A retrospective study identified platelet count as a risk marker for clinically significant bleeding. We conducted a study to examine any association of platelet count, international normalized ratio, and activated partial thromboplastin time with bleeding risk in PICU patients. DESIGN: Prospective observational cohort study. SETTING: The PICU at the Children's Hospital of Eastern Ontario, a university-affiliated tertiary care pediatric center. PATIENTS: Consecutive patients admitted to the PICU. Exclusion criteria were prior inclusion, admission with bleeding, inherited bleeding disorders, weight less than 3 kg, and age less than 60 days or 18 years or more. INTERVENTIONS: There were no interventions in this observational study. MEASUREMENTS AND MAIN RESULTS: Patients were monitored in real time for clinically significant bleeding, using a broadly inclusive definition of clinically significant bleeding, for up to 72 hours after admission to the PICU, or until death or discharge. All measurements of platelet count, international normalized ratio, and activated partial thromboplastin time obtained during the study period were included as time-varying covariates in Cox proportional hazard models. Two hundred thirty-four patients were eligible, and 25 (11%) had one or more episodes of clinically significant bleeding. Platelet count was associated with increased hazard of clinically significant bleeding (hazard ratio, 0.96 per 10 × 10/L increase in platelet count; 95% CI (0.93-0.997; p = 0.03). Increasing hazard for clinically significant bleeding was seen with decreasing platelet count. Neither international normalized ratio nor activated partial thromboplastin time was significantly associated with clinically significant bleeding. CONCLUSIONS: There is a statistically significant association in PICU patients between decrease in platelet count and clinically significant bleeding, and this association is stronger with lower platelet counts. Further study is required to determine whether platelet transfusion can reduce bleeding risk. International normalized ratio and activated partial thromboplastin time do not predict clinically significant bleeding, and these tests should not be used for this purpose in a general PICU patient population.

Rapid acquisition of immunologic tolerance to factor VIII and disappearance of anti-factor VIII IgG4 after prophylactic therapy in a hemophilia A patient with high-titer factor VIII inhibitor.

We report an 11-month-old boy with severe hemophilia A who had regular exposure to factor VIII (FVIII) intended to reduce the risk of developing an inhibitor. He developed a high-titer inhibitor (peak titer 19 BU) that disappeared within 6 weeks of starting immune tolerance induction (ITI). Anti-FVIII IgG4 peaked briefly compared with anti-FVIII IgG1 and the Bethesda titer. Neither rapid resolution of an inhibitor after prophylaxis nor this behavior of anti-FVIII IgG4 has been previously reported. Transient anti-FVIII IgG4 may be a marker of an attenuated anti-FVIII response induced by prophylactic FVIII therapy.

Pediatric pulmonary thromboembolism: a 3-year Canadian Pediatric Surveillance Program study.

BACKGROUND: Pediatric pulmonary embolism (PE) is a rare event associated with significant morbidity and mortality. Awareness of clinical presentation and practices unique to children may aid clinicians in prompt identification and treatment. OBJECTIVES: To describe the incidence, risk factors, clinical presentation, diagnostic and therapeutic practices, and short-term outcomes of pediatric PE. METHODS: We conducted a 3-year national surveillance study through the Canadian Pediatric Surveillance Program. Over 2800 pediatric specialists and subspecialists were contacted monthly from 2020 to 2022 and requested to report all new cases of PE in patients up to 18 years of age. Case-specific data were obtained through voluntary completion of a detailed questionnaire. RESULTS: Fifty-eight cases (78% female, n = 45) were reported (2.4 cases per million children), with rates highest in adolescents 15 to 18 years (6.6 cases per million). Detailed information, available for 31 (53%) cases, documented at least 1 risk factor in 28 (90%) cases; 24 (77%) patients presented with 2 or more symptoms. Computed tomography pulmonary angiography was used for diagnostic confirmation in 25 (81%) cases. Anticoagulation was initiated in 24 (77%) of 31 cases; fewer than 5 patients underwent thrombolysis or surgical interventions. Of 28 patients who received therapeutic interventions, 8 (29%) experienced treatment-related complications. Fewer than 5 mortalities were reported. CONCLUSION: Pediatric PE is a rare event, with female adolescents at the highest risk. Although the presentation is often nonspecific, clinicians should maintain a high index of suspicion, particularly in patients with risk factors and when other diagnoses that may explain symptoms have been excluded.

Access to innovative therapies in pediatric oncology: Report of the nationwide experience in Canada.

BACKGROUND: The need for new therapies to improve survival and outcomes in pediatric oncology along with the lack of approval and accessible clinical trials has led to "out-of-trial" use of innovative therapies. We conducted a retrospective analysis of requests for innovative anticancer therapy in Canadian pediatric oncology tertiary centers for patients less than 30 years old between 2013 and 2020. METHODS: Innovative therapies were defined as cancer-directed drugs used (a) off-label, (b) unlicensed drugs being used outside the context of a clinical trial, or (c) approved drugs with limited evidence in pediatrics. We excluded cytotoxic chemotherapy, cellular products, and cytokines. RESULTS: We retrieved data on 352 innovative therapy drug requests. Underlying diagnosis was primary CNS tumor 31%; extracranial solid tumor 37%, leukemia/lymphoma 22%, LCH 2%, and plexiform neurofibroma 6%. RAS/MAP kinase pathway inhibitors were the most frequently requested innovative therapies in 28% of all requests followed by multi-targeted tyrosine kinase inhibitors (17%), inhibitors of the PIK3CA-mTOR-AKT pathway (8%), immune checkpoints inhibitors (8%), and antibody drug conjugates (8%). In 112 out of 352 requests, innovative therapies were used in combination with another anticancer agent. 48% of requests were motivated by the presence of an actionable molecular target. Compassionate access accounted for 52% of all requests while public insurance was used in 27%. Mechanisms of funding varied between provinces. CONCLUSION: This real-world data collection illustrates an increasing use of "out-of-trial" innovative therapies in pediatric oncology. This new field of practice warrants further studies to understand the impact on patient trajectory and equity in access to innovative therapies.

A survey of the management of newborns with severe hemophilia in Canada.

OBJECTIVE: To determine the practice patterns of Canadian hematologists and neonatologists/paediatricians who care for newborns with hemophilia, with regard to vitamin K administration, use of empirical clotting factor replacement therapy, neuroimaging and timing of hematology consultation. METHODS: Hematologists and neonatologists/paediatricians, identified from membership lists of Canadian professional organizations, were provided electronic and/or paper versions of the survey instrument. Questions were posed in the context of specific clinical scenarios. Differences in response proportions between groups were compared for selected questions. RESULTS: There were 171 respondents among 616 eligible persons who were sent the survey; 58 respondents had recent experience managing a newborn with hemophilia. There was a consensus not to provide empirical treatment to well newborns after uncomplicated deliveries, to provide empirical treatment to symptomatic newborns and to obtain neuroimaging for symptomatic newborns. Systematic differences between hematologists and neonatologists/paediatricians existed with regard to the timing of hematology consultation when the diagnosis of hemophilia had not been confirmed antenatally, the route of vitamin K administration for newborns with hemophilia and the choice of product to use for empirical treatment of a symptomatic newborn. CONCLUSIONS: The observed lack of consensus regarding important management decisions indicates a need for ongoing research in the care of newborns with hemophilia. Systematic differences between hematologists and neonatologists/paediatricians suggest a role for improved communication and collaboration between these two groups of practitioners.

OBJECTIF: Déterminer les profils de pratique des hématologues et des néonatologistes/pédiatres canadiens qui soignent des nouveau-nés hémophiles à l'égard de l'administration de vitamine K, de l'utilisation empirique du traitement par le facteur de remplacement de coagulation, de la neuro-imagerie et du moment de la consultation en hématologie. MÉTHODOLOGIE: Les hématologues et les néonatologistes/pédiatres, repérés grâce aux listes de membres d'organismes professionnels canadiens, ont reçu une version virtuelle, une version papier ou les deux versions du sondage. Les questions étaient posées dans le contexte de scénarios cliniques précis. Les différences dans les proportions de réponses entre les groupes étaient comparées à l'égard de questions sélectionnées. RÉSULTATS: Sur les 616 personnes admissibles, 171 ont répondu au sondage. De ce nombre, 58 avaient eu une expérience récente de prise en charge d'un nouveau-né hémophile. On observait un consensus de ne pas administrer de traitement empirique aux nouveau-nés en santé après un accouchement sans complication, d'administrer un traitement empirique aux nouveau-nés symptomatiques et d'obtenir une neuroimagerie chez ces nouveau-nés symptomatiques. Il y avait des différences systématiques entre les hématologues et les néonatologistes/pédiatres pour ce qui est du moment de la consultation en hématologie lorsque le diagnostic n'avait pas été confirmé pendant la période anténatale, de la voie d'administration de la vitamine K aux nouveau-nés hémophiles et du choix de produit à utiliser pour administrer un traitement empirique à un nouveau-né symptomatique. CONCLUSIONS: L'absence de consensus observé au sujet d'importantes décisions de prise en charge démontre la nécessité de poursuivre les recherches sur les soins aux nouveau-nés hémophiles. En raison des différences systématiques entre les hématologues et les néonatologistes/pédiatres, il y aurait lieu d'améliorer les communications et la collaboration entre ces deux groupes de praticiens.

Extracellular vesicle small RNA cargo discriminates non-cancer donors from pediatric B-lymphoblastic leukemia patients.

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.

Emicizumab in people with moderate or mild haemophilia A (HAVEN 6): a multicentre, open-label, single-arm, phase 3 study.

BACKGROUND: Clinical trial data are scarce for the use of prophylaxis in people with non-severe haemophilia A. The HAVEN 6 study aims to assess safety and efficacy of emicizumab prophylaxis in people with non-severe haemophilia A without factor VIII (FVIII) inhibitors. METHODS: HAVEN 6 is a multicentre, open-label, single-arm, phase 3 study taking place in 22 specialty clinics and hospitals in Europe, North America, and South Africa. Eligible participants were people of all ages weighing at least 3 kg with a diagnosis of moderate (FVIII activity ≥1%-≤5%) or mild (FVIII >5%-<40%) haemophilia A without FVIII inhibitors requiring prophylaxis as assessed by the treating physician. Participants received subcutaneous emicizumab 3 mg/kg of bodyweight once weekly for 4 weeks, followed by the participant's choice of maintenance dose: 1·5 mg/kg once weekly, 3 mg/kg every 2 weeks, or 6 mg/kg every 4 weeks. Safety was the primary objective of the study. Safety endpoints included adverse events, serious adverse events, and adverse events of special interest including thromboembolic events and thrombotic microangiopathies. The primary efficacy endpoint was the annualised bleed rate for treated bleeds. Analyses were done for participants who received at least one dose of emicizumab. This study is registered with ClinicalTrials.gov, number NCT04158648, and is active but not recruiting. FINDINGS: Between Feb 10, 2020, and Aug 31, 2021, we assigned 73 people to treatment. 72 participants received at least one dose of emicizumab (51 moderate [71%]; 21 mild [29%]; 69 male [96%]; three female [4%]; and 61 White [85%]). Median age was 23·5 years (IQR 12·0-36·0); median follow-up was 55·6 weeks (IQR 52·3-61·6) weeks. At baseline, 24 participants (33%) had target joints and 37 (51%) were receiving FVIII prophylaxis. 60 participants (83%) had at least one adverse event; the most common adverse events were headache (in 12 participants [17%]), injection-site reaction (12 [17%]), and arthralgia (11 [15%]). 15 (21%) had at least one emicizumab-related adverse event; no adverse events led to treatment withdrawal, modification, or interruption. Eight participants (11%) reported ten serious adverse events in total, none emicizumab-related. There were no deaths or thrombotic microangiopathies. One participant had grade 1 thrombosed haemorrhoids (classified as a thromboembolic event), unrelated to emicizumab. The annualised bleed rate was 0·9 (95% CI 0·55-1·52) for treated bleeds. 48 participants (67%) had no treated bleeds. All-bleed annualised bleed rates were 10·1 (95% CI 6·93-14·76) from 24 weeks pre-study and 2·3 (1·67-3·12) on-study after a median follow-up of 55·6 weeks. INTERPRETATION: These data show efficacy and a favourable safety profile of emicizumab in people with non-severe haemophilia A without FVIII inhibitors who warrant prophylaxis, confirming emicizumab as a valuable treatment option in this population. FUNDING: F Hoffmann-La Roche.