Background Hematopoietic stem cell transplantation can be curative for children with difficult to treat leukemia. The conditioning regimen utilised is known to influence outcomes. We report outcomes of the conditioning regimen used at the Alberta Children’s Hospital, consisting of busulfan (with pharmacokinetic target of 3750μmol*min/day +/-10%) for 4 days, higher dose (250 mg/m2) fludarabine and 400 centigray of total body irradiation. Procedure This retrospective study involved children receiving transplant for acute lymphoblastic leukemia (ALL). It compared children who fell within the target range for busulfan with those who were either not measured or were measured and fell outside this range. All other treatment factors were identical. Results Twenty-nine children (17 within target) were evaluated. All subjects engrafted neutrophils with a median (IQR) time of 14 days (8-30 days). The cumulative incidence of acute graft versus host disease was 44.8% (95% CI 35.6 – 54.0%), while chronic graft versus host disease was noted in 16.0% (95% CI 8.7% - 23.3%). At two years, the overall survival was 78.1% (95% CI 70.8% - 86.4%) and event free survival was 74.7% (95% CI 66.4% - 83.0%). Cumulative incidence of relapse was 11.3% (95% CI 5.1% - 17.5%). There were no statistically significant differences in between the group that received targeted busulfan compared with the untargeted group. Conclusion The current regimen used in children with ALL results in outcomes comparable to standard treatment with acceptable toxicities and significant reduction in radiation dose. Targeting Busulfan dose in this cohort did not result in improved outcomes.

Low glomerular filtration rate (GFR) prior to stem cell transplant (SCT) is associated with increased morbidity and mortality. The implications of abnormally high GFRs, or glomerular hyperfiltration, prior to SCT are unknown. Twenty two of 74 consecutive pediatric SCT patients over 2 years old at a single center were hyperfiltrating prior to SCT, median nuclear medicine GFR 154 mL/min/1.73 m 2 (IQR 146, 170). There was no association between any demographic and hyperfiltration, nor between hyperfiltration and acute kidney injury ( P = 0.8), renal replacement therapy ( P = 0.63), event-free survival ( P = 1), or chronic kidney disease ( P = 0.73).

The incidence of secondary malignancies associated with busulfan exposure is considered low, but has been poorly characterized. Because this alkylating agent is increasingly utilized as conditioning prior to gene therapy in non-malignant hematologic and related disorders, more precise characterization of busulfan’s potential contribution to subsequent malignant risk is warranted. We conducted a literature-based assessment of busulfan and subsequent late effects, with emphasis on secondary malignancies, identifying publications via PubMed searches and selecting those reporting at least 3 years of follow-up. We identified 8 pediatric and 13 adult publications describing long-term follow-up in 570 pediatric and 2,076 adult hematopoietic cell transplant (HCT) recipients. Secondary malignancies were reported in 0.5% of pediatric HCT recipients, with no cases of myelodysplastic syndrome (MDS) or acute myelocytic leukemia (AML). Fatal secondary malignancies were reported in 0.8% of 1887 evaluable adult HCT recipients, and an overall incidence of secondary malignancies of 4.8% was reported in a subset of 389 evaluable adult patients. We also reviewed long-term results from 8 publications evaluating lentiviral- and human promotor-based HSC-targeted gene therapy in 215 patients with non-malignant conditions, in which busulfan/treosulfan monotherapy or busulfan/fludarabine was the only conditioning. Two malignancies were reported in patients with Sickle Cell Disease (SCD), one of which was potentially busulfan-related. No additional malignancies were reported in 173 patients with follow-up of 5-12 years. The incidence of busulfan-related secondary malignancies is low, and likely to be substantially less than 1% in pediatric transplant recipients, especially those receiving busulfan monotherapy for non-malignant conditions other than SCD.

The probability of silent cerebral infarcts (SCIs) is high among individuals with sickle cell anemia (SCA). The American Society of Hematology’s (ASH) guidelines recommend at least one non-sedated magnetic resonance image (MRI) in the SCA population. Implementing ASH guidelines in low-middle-income settings requires training non-neuroradiologists. We hypothesize that three general radiologists located in Nigeria will achieve a high level of agreement when assessed against a reference set of brain MRIs previously adjudicated for the presence of SCIs. Consensus evaluation utilizing MRIs from the axial and coronal planes by the radiologists revealed an excellent or substantial agreement with reference MRI scans. Thus, radiologists can detect SCIs comparable with board-certified radiologists.

Both vinblastine and low dose cytarabine therapy for Langerhans cell histiocytosis (LCH) have historically been delivered intravenously. Due to a vinblastine shortage and the SARS-CoV2 pandemic, frontline subcutaneous cytarabine was used to treat six pediatric patients with LCH with greater than 93% of the cytarabine doses administered at home by family. On average, 164 infusion chair hours (65.7 infusions) and 5,607 miles of driving were saved per patient, highlighting that subcutaneous cytarabine is a feasible treatment option for pediatric patients with LCH resulting in notably decreased patient travel burden and infusion center utilization.

Background Childhood cancer is the sixth leading cause of global cancer burden. Indeed, 90% of childhood cancer cases occur in low-middle-income countries (LMICs), where mortality can be 4-5 times higher than in high income settings. In addition, many LMICs lack data on pediatric oncology for policy development and resource prioritization. In this paper, we describe the state of pediatric cancer care and treatment in Cameroon. Procedure We conducted cross-sectional survey in July 2020, which enabled us to collect data from two hospitals providing pediatric oncology services in Cameroon. We collected data on service availability, human resource capacity, frequent cancer types, treatment dropout, primary reasons for drop out, disclosure of status, and management of oncology data. Result The surveyed hospitals offered both pediatric chemotherapy and palliative care services; however, none offered nuclear medicine or radiotherapy services. In terms of workforce, human resources were grossly lacking in both hospitals. The available ones include one pediatric hemato-oncologist, one medical oncologist, one resident pediatric oncologist, one pediatric surgeon, and 14 oncology nurses and about 40% (18/45) of have received specialty training in oncology. The commonest childhood cancer managed in these facilities, was Burkitt lymphoma, (39, 23%). About 30% of children on chemotherapy abandoned their treatment, primarily due to lack of funds to continue with treatment sessions. In both settings, the capacity to diagnose cancer and provide counselling was limited. In addition, the tools to capture and transmit data varied by facility, resulting to different data set being generated. Furthermore, both facilities, had no schedule and timelines for data reporting. Conclusions Our results suggest that several factors negatively impact proper cancer care and treatment of pediatric Cancers in Cameroon. These include, inadequate human resource capacity, a high proportion of dropouts from chemotherapy due to high cost, and lack of harmonized data collection and reporting tools and systems. Systematically addressing these factors could contribute to improving treatment outcomes for pediatric cancer patients in Cameroon.

Coagulation factors used in prophylactic treatment of patients with clotting disorders are associated with significant costs to health care systems. These products have complex pharmacokinetic profiles subject to large inter-individual variation making their efficient use challenging. Prior to this project, pharmacists were not involved as part of the Hemophilia care teams across Canada. The purpose of this pilot project was to determine whether employment of a pharmacist with expertise and a focus on plasma protein and related products including hemophilia treatments, would be an effective strategy to reduce costs associated with clotting factor prophylaxis regimens and identify the pharmacist’s activities associated with this new role. A cost-minimization analysis was conducted to compare the addition of a pharmacist to the care team of the Hemophilia Treatment Centre (HTC) at a pediatric hospital serving 500,000 children and youth. The analysis was performed from the perspective of the formulary manager, Canadian Blood Services, over a 1-year period including 9 months of interventions. The pharmacist performed 18 therapeutic optimizations on 14 patients with moderate to severe hemophilia A or B, and 1 von Willebrand patient, aged 3 to 18 years old. As a result of the pharmacist’s intervention, clotting factor treatment costs extrapolated over one year were reduced by 20.5% for these patients. This represents a net savings of $225K CAD/year, or $12.5K CAD/optimization/year. The addition of a pharmacist to the HTC to manage recombinant and plasma-derived coagulation factors can optimise the treatment plan and significantly reduce the costs of managing patients with hemophilia.

Extracorporeal photopheresis (ECP) has proven effective in the treatment of several diseases, including acute and chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. In its standard version, ECP requires leukapheresis to obtain a fraction of mononuclear cells. The possibility of using leukapheresis is limited by the requirements for vascular access and the somatic status of the patient. We have developed a new ECP method that does not require leukapheresis. This paper presents a description of two clinical cases of severe refractory GVHD treated by micro-ECP.

Objectives: Sickle cell disease (SCD) is well recognized as a hypercoagulable state, however venous thromboembolism (VTE) risk factors in children remain largely unknown. In this study, we aim to describe the clinical characteristics, outcomes and recurrence of hospital acquired VTE in patients younger than 21 years of age. Study Design/Methods: Data were extracted from electronic medical records over a 10-year period (2011-2021). Data regarding sickle cell genotype, demographics, reason for admission, location of thrombus, presence of central venous catheter (CVC), intensive care unit (ICU) admission, presence of thrombophilia risk factors, resolution of VTE, mortality, and bleeding outcomes on anticoagulation were collected. Recurrence of VTE at 1 and 5 years was assessed. Descriptive statistics were used as indicated. Results: We identified a total of 21 VTE events over the ten-year study period. Six of these events occurred in those younger than 12 years of age. Fifteen (71%) VTE events occurred in the HbSS or HbSβThal 0 genotypes compared to 8 (29%) in HbSC. Eleven (52%) patients were admitted with acute chest syndrome (ACS). Most VTE events were associated with ICU admissions (n=13, 62%) and presence of central venous catheter (n=12, 57%). Major bleeding on anticoagulation occurred in 10%.All patients had resolution of index VTE at 12 weeks. Recurrence rate for VTE at 5 years was 13%. One patient died from the VTE event. Conclusions: Our study highlights that VTE can complicate SCD in children and young adults. Hospital acquired VTE were most associated with ICU admission, CVC, and ACS, but larger studies are indicated to validate our findings.

Aim: To explore the validity and strength of evidence on the association between environmental factors and risk of developing childhood (0-14 years) cancer. Methods: An umbrella review was conducted including systematic reviews and meta-analyses of observational epidemiological studies that examined the association of any environmental exposure of either parent or child with any type of childhood cancer. PubMed and Scopus databases were searched until April 2020. Based on predefined criteria, the evidence was graded into strong, highly suggestive, suggestive or weak. Results: 509 meta-analyses explored environmental exposures and risk of developing 10 different types of childhood cancer. Only 2.4% of the associations were considered to have highly suggestive evidence inferred by strongly statistically significant results. These associations were confined to increased risk of overall leukemia, especially acute lymphoblastic leukemia (ALL), in relation to high birthweight, paternal smoking and exposure to pesticides, particularly insecticides. By contrast, maternal multivitamin supplementation during pregnancy (summary odds ratio [OR]: 0.64, 95% confidence intervals [CI]: 0.52, 0.80) and breastfeeding for more than 6 months (summary OR: 0.76, 95%CI: 0.68, 0.84) were supported by highly suggestive evidence for decreased risk of ALL. There was also highly suggestive evidence for increased risk of central nervous system (CNS) tumors, especially astrocytoma, in relation to high birthweight, as well as increased risk of testicular cancer in relation to testicular microlithiasis and isolated cryptorchidism. Conclusions: The present findings provide evidence that exposure to seven maternal/neonatal factors significantly affects the risk of childhood leukemia, CNS tumors and testicular cancer. Further evidence from sufficiently powered studies and large consortia with uniform reporting of analyses is needed to allow firmer conclusions to be drawn.

a succesfull combination therapy with tagraxofusp-erz plus venetoclax for a pediatric case of Blastic plasmacytoid dendritic cell neoplasm brıdgıng to transplantBaşak Adaklı Aksoy 1,Selime Aydoğdu1,Özlem Başoğlu Öner 1,Gizem Zengin Ersoy 1,Funda Erol Çipe1, Ayşe Gonca Kaçar3, Zafer Başlar 3,Tiraje Celkan 3,Tunç Fışgın1,Ceyhun Bozkurt 21Altınbaş Üniversitesi Tıp Fakültesi, Medical Park Bahçelievler Hastanesi2İstinye Üniversitesi Tıp Fakültesi , Pediatrik Hematoloji- Onkoloji Bölümü3İstanbul Üniversitesi, Cerrahpaşa Tıp Fakültesi

Abstract Background and aims Multidisciplinary team (MDT) meetings provide a regular, structured meeting of a core group of professionals to provide expert decision-making in individual patient care. We describe our experiences in establishing a virtual pediatric oncology MDT between twinning partners in Cameroon (4 hospitals) and the UK. Methods Monthly video conferencing MDT meetings were established in March 2019, initially using Google meet then using Zoom platforms. Case details were circulated using formal proformas. Standard operating procedures were outlined for the MDT conduct. Results There have been 269 discussions of 201 patients in 21 meetings. Patients have been varied in age (up to 24 years). Eighty-seven (43.3%) patients had NHL, 16 (8.0%) had Wilms tumour, 20 (10.0%) had Acute Lymphoblastic Leukaemia, 19 (9.5%) had Retinoblastoma and 59 (29.4%) had other malignancies. Four of the patients did not have a malignancy. The majority of patients had stage 3 (51, 45.1%) or stage 4 (59, 52.2%). Nine patients had relapsed disease. Core team members reported positive benefits from the MDT, including defining goals of care, shared decision making, professional education and team-building. Conclusions Virtual MDT meetings between geographically dispersed teams are possible and have proved particularly valuable during the COVID-19 pandemic when in-person visits are not permitted. Cancer treatment cannot be done in isolation; the regular MDT meetings have paved the way for informed care through regular consultancy.

Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal syndrome of immune dysregulation that is classified into primary and secondary forms. The standard of care is established with dexamethasone and etoposide, but there are currently no guidelines for refractory HLH or cases triggered by infection or malignancy. [1] We describe here a series of pediatric patients with malignancy-associated HLH (m-HLH) to discuss the complexities in the initial diagnostic considerations, the balance of therapeutic regimens and their toxicities, and the novel use of emapalumab and ruxolitinib in patients with refractory disease.

Background Pediatric anticancer drug development has numerous challenges. Pediatric Research Equity Act (PREA) and the Best Pharmaceuticals for Children Act (BPCA), has been put forth to address the deficiency in pediatric drug development in general. Until recently, the requirement for pediatric evaluation of most oncology products for adult cancers was waived, because children typically do not have adult-type cancers or the indication or drug had been granted orphan designation. PREA therefore had no impact. Pediatric studies for labeling updates are largely done through BPCA by a Written Request (WR), issued by FDA. Because pediatric and adult populations do not share the same biology, natural history, or disease progression, there are limited opportunities to extrapolate adult information to pediatric. The requirements for the pediatric studies can vary greatly. Procedure In this study, we searched WRs that were issued by the FDA since 2001. We found 42 requests for pediatrics in oncology drugs and biologics. Results Studies included in 25 of the WRs have concluded, 18 have been given exclusivity, and 4 drugs have been approved for use in pediatric populations. The current status of the WRs are presented from regulatory, study design, dosing, formulation, analysis plan, evidential standard of efficacy and safety. Conclusions This would serve the purposes to study what has been requested over the years and what have been completed in response to the requirements. We consider this to be the anchor of pediatric cancer development for current stage and can potentially provide insight on how pediatric cancer drug development would change for the future years.