IT-Related Barriers and Facilitators to the Implementation of a New European eHealth Solution, the Digital Survivorship Passport (SurPass Version 2.0): Semistructured Digital Survey.

BACKGROUND: To overcome knowledge gaps and optimize long-term follow-up (LTFU) care for childhood cancer survivors, the concept of the Survivorship Passport (SurPass) has been invented. Within the European PanCareSurPass project, the semiautomated and interoperable SurPass (version 2.0) will be optimized, implemented, and evaluated at 6 LTFU care centers representing 6 European countries and 3 distinct health system scenarios: (1) national electronic health information systems (EHISs) in Austria and Lithuania, (2) regional or local EHISs in Italy and Spain, and (3) cancer registries or hospital-based EHISs in Belgium and Germany. OBJECTIVE: We aimed to identify and describe barriers and facilitators for SurPass (version 2.0) implementation concerning semiautomation of data input, interoperability, data protection, privacy, and cybersecurity. METHODS: IT specialists from the 6 LTFU care centers participated in a semistructured digital survey focusing on IT-related barriers and facilitators to SurPass (version 2.0) implementation. We used the fit-viability model to assess the compatibility and feasibility of integrating SurPass into existing EHISs. RESULTS: In total, 13/20 (65%) invited IT specialists participated. The main barriers and facilitators in all 3 health system scenarios related to semiautomated data input and interoperability included unaligned EHIS infrastructure and the use of interoperability frameworks and international coding systems. The main barriers and facilitators related to data protection or privacy and cybersecurity included pseudonymization of personal health data and data retention. According to the fit-viability model, the first health system scenario provides the best fit for SurPass implementation, followed by the second and third scenarios. CONCLUSIONS: This study provides essential insights into the information and IT-related influencing factors that need to be considered when implementing the SurPass (version 2.0) in clinical practice. We recommend the adoption of Health Level Seven Fast Healthcare Interoperability Resources and data security measures such as encryption, pseudonymization, and multifactor authentication to protect personal health data where applicable. In sum, this study offers practical insights into integrating digital health solutions into existing EHISs.

Vaccination practices in pediatric transplantation: A survey among member centers of the European reference network TransplantChild.

BACKGROUND: There is considerable variation in vaccination practices between pediatric transplant centers. This study aims to evaluate active immunization attitudes and practices among ERN-TransplantChild centers and identify potential areas of improvement that could be addressed by shared evidence-based protocols. METHODS: A cross-sectional questionnaire of attitudes and practices toward immunization of pediatric SOT and HSCT candidates and recipients was sent to a representative member of multidisciplinary teams from 27 European centers belonging to the ERN-TransplantChild. RESULTS: A total of 28/62 SOT programs and 6/12 HSCT programs across 21 European centers participated. A quarter of centers did not have an on-site protocol for the immunizations. At the time of transplantation, pediatric candidates were fully immunized (80%-100%) in 57% and 33% of the SOT and HSCT programs. Variations in the time between vaccine administration and admission to the waiting list were reported between the centers, with 2 weeks for inactivated vaccines and variable time (2-4 weeks) for live-attenuated vaccines (LAVs). Almost all sites recommended immunization in the post-transplant period, with a time window of 4-8 months for the inactivated vaccines and 16-24 months for MMR and Varicella vaccines. Only five sites administer LAVs after transplantation, with seroconversion evaluated in 80% of cases. CONCLUSIONS: The immunization coverage of European pediatric transplant recipients is still inconsistent and far from adequate. This survey is a starting point for developing shared evidence-based immunization protocols for safe vaccination among pediatric transplant centers and generating new research studies.

Therapeutic Perspectives for the Clinical Application of Umbilical Cord Hematopoietic and Mesenchymal Stem Cells: Overcoming Complications Arising After Allogeneic Hematopoietic Stem Cell Transplantation.

This review focuses on the therapeutic features of umbilical cord blood (UCB) cells as a source for allogeneic hematopoietic stem cell transplantation (aHSCT) in adult and child populations to treat malignant and nonmalignant hematologic diseases, genetic disorders, or pathologies of the immune system, when standard treatment (e.g., chemotherapy) is not effective or clinically contraindicated. In this article, we summarize the immunological properties and the advantages and disadvantages of using UCB stem cells and discuss a variety of treatment outcomes using different sources of stem cells from different donors both in adults and pediatric population. We also highlight the critical properties (total nucleated cell dose depending on HLA compatibility) of UCB cells that reach better survival rates, reveal the advantages of double versus single cord blood unit transplantation, and present recommendations from the most recent studies. Moreover, we summarize the mechanism of action and potential benefit of mesenchymal umbilical cord cells and indicate the most common posttransplantation complications.

Rubella vaccine-induced granulomas are a novel phenotype with incomplete penetrance of genetic defects in cytotoxicity.

BACKGROUND: Rubella virus-induced granulomas have been described in patients with various inborn errors of immunity. Most defects impair T-cell immunity, suggesting a critical role of T cells in rubella elimination. However, the molecular mechanism of virus control remains elusive. OBJECTIVE: This study sought to understand the defective effector mechanism allowing rubella vaccine virus persistence in granulomas. METHODS: Starting from an index case with Griscelli syndrome type 2 and rubella skin granulomas, this study combined an international survey with a literature search to identify patients with cytotoxicity defects and granuloma. The investigators performed rubella virus immunohistochemistry and PCR and T-cell migration assays. RESULTS: This study identified 21 patients with various genetically confirmed cytotoxicity defects, who presented with skin and visceral granulomas. Rubella virus was demonstrated in all 12 accessible biopsies. Granuloma onset was typically before 2 years of age and lesions persisted from months to years. Granulomas were particularly frequent in MUNC13-4 and RAB27A deficiency, where 50% of patients at risk were affected. Although these proteins have also been implicated in lymphocyte migration, 3-dimensional migration assays revealed no evidence of impaired migration of patient T cells. Notably, patients showed no evidence of reduced control of concomitantly given measles, mumps, or varicella live-attenuated vaccine or severe infections with other viruses. CONCLUSIONS: This study identified lymphocyte cytotoxicity as a key effector mechanism for control of rubella vaccine virus, without evidence for its need in control of live measles, mumps, or varicella vaccines. Rubella vaccine-induced granulomas are a novel phenotype with incomplete penetrance of genetic disorders of cytotoxicity.

Changes in Nutritional Status during Induction Phase and Their Association with Fever and Minimal Residual Disease in Paediatric Acute Lymphoblastic Leukaemia.

Background and objectives: Acute lymphoblastic leukaemia (ALL) is associated with a cytokine imbalance and oxidative stress, which can be aggravated by malnutrition. Malnutrition, defined by the World Health Organisation (WHO) as obesity or undernutrition, can affect treatment complications and outcomes. Therefore, we aimed to analyse the change in the body mass index (BMI) z-score during induction, as well as evaluate the impact of childhood malnutrition on fevers at an ALL presentation and early response to therapy. Methods: An observational cohort study of 50 consecutive children with ALL, diagnosed in 2019-2022, was performed. Patients were divided into age groups of 0-5, 6-11, and 12-17 years. BMI-for-age z-scores were used to define undernutrition and overnutrition according to WHO growth standards. Results: The number of patients with an abnormal BMI increased from 3 (6%) at diagnosis to 10 (20%) at the end of induction (from 2 (4%) to 6 (12%) in overweight/obese, and from 1 (2%) to 4 (8%) in underweight patients). At the end of induction, all overweight/obese patients were 0-5 years old. On the other hand, a statistically significant decrease in the mean BMI z-score among patients aged 12-17 was observed (p = 0.005). The mean BMI z-score differed statistically significantly among children aged 0-5 presenting with and without fever (p = 0.001). The minimal residual disease (MRD) level at the end of induction was not related to BMI at diagnosis. Conclusions: Despite the use of steroids, adolescents are prone to losing weight during an ALL induction, in contrast to preschool children, who tend to gain weight under the same treatment. BMI at diagnosis was related to a fever of ≥38 °C (at ALL presentation) in the 0-5 age group. The results emphasise the importance of careful nutritional status monitoring, with younger and older children as important target groups for weight gain and weight loss interventions, respectively.

Development of a questionnaire to evaluate female fertility care in pediatric oncology, a TREL initiative.

BACKGROUND: Currently the five-year survival of childhood cancer is up to 80% due to improved treatment modalities. However, the majority of childhood cancer survivors develop late effects including infertility. Survivors describe infertility as an important and life-altering late effect. Fertility preservation options are becoming available to pre- and postpubertal patients diagnosed with childhood cancer and fertility care is now an important aspect in cancer treatment. The use of fertility preservation options depends on the quality of counseling on this important and delicate issue. The aim of this manuscript is to present a questionnaire to determine the impact of fertility counseling in patients suffering from childhood cancer, to improve fertility care and evaluate what patients and their parents or guardians consider good fertility care. METHODS: Within the framework of the EU-Horizon 2020 TREL project, a fertility care evaluation questionnaire used in the Netherlands was made applicable for international multi-center use. The questionnaire to be used at least also in Lithuania, incorporates patients' views on fertility care to further improve the quality of fertility care and counseling. Results evaluate fertility care and will be used to improve current fertility care in a national specialized pediatric oncology center in the Netherlands and a pediatric oncology center in Lithuania. CONCLUSION: An oncofertility-care-evaluation questionnaire has been developed for pediatric oncology patients and their families specifically. Results of this questionnaire may contribute to enhancement of fertility care in pediatric oncology in wider settings and thus improve quality of life of childhood cancer patients and survivors.

Low incidence of ABL-class and JAK-STAT signaling pathway alterations in uniformly treated pediatric and adult B-cell acute lymphoblastic leukemia patients using MRD risk-directed approach - a population-based study.

BACKGROUND: ABL-class and JAK-STAT signaling pathway activating alterations have been associated with both a poor post-induction minimal residual disease (MRD) response and an inferior outcome in B-cell acute lymphoblastic leukemia (B-ALL). However, in most of the studies patients received non-uniform treatment. METHODS: We performed a population-based analysis of 160 (122 pediatric and 38 adult) Lithuanian BCR-ABL1-negative B-ALL patients who had been uniformly treated according to MRD-directed NOPHO ALL-2008 protocol. Targeted RNA sequencing and FISH analysis were performed in cases without canonical B-ALL genomic alterations (high hyperdiploids and low hypodiploids included). RESULTS: We identified ABL-class fusions in 3/160 (1.9%) B-ALL patients, and exclusively in adults (p = 0.003). JAK-STAT pathway fusions were present in 4/160 (2.5%) cases. Of note, P2RY8-CRLF2 fusion was absent in both pediatric and adult B-ALL cases. Patients with ABL-class or JAK-STAT pathway fusions had a poor MRD response and were assigned to the higher risk groups, and had an inferior event-free survival (EFS) / overall survival (OS) compared to patients without these fusions. In a multivariate analysis, positivity for ABL-class and JAK-STAT fusions was a risk factor for worse EFS (p = 0.046) but not for OS (p = 0.278) in adults. CONCLUSIONS: We report a low overall frequency of ABL-class and JAK-STAT fusions and the absence of P2RY8-CRLF2 gene fusion in the Lithuanian BCR-ABL1 negative B-ALL cohort. Future (larger) studies are warranted to confirm an inferior event-free survival of ABL-class/JAK-STAT fusion-positive adult patients in MRD-directed protocols.

Salivary gland carcinoma in children and adolescents: The EXPeRT/PARTNER diagnosis and treatment recommendations.

Salivary gland carcinomas (SGCs) are rare during childhood and adolescence. Consequently, no standardized recommendations for the diagnosis and therapeutic management of pediatric SGC are available, and pediatric oncologists and surgeons generally follow adult guidelines. Complete surgical resection with adequate margins constitutes the cornerstone of treatment. However, the indications and modalities of adjuvant therapy remain controversial and may be challenging in view of the potential long-term toxicities in the pediatric population. This paper presents the consensus recommendations for the diagnosis and treatment of children and adolescents with SGCs, established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the EU-funded PARTNER project (Paediatric Rare Tumours Network - European Registry).

Pleuropulmonary blastoma in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations.

Pleuropulmonary blastoma (PPB) is a rare cancer occurring mainly during early childhood and often associated with germline DICER1 mutations. It is classified by the macroscopic appearance into three interrelated clinico-pathologic entities on a developmental continuum. Complete tumor resection is a main prognostic factor and can be performed at diagnosis or after neoadjuvant treatment that includes chemotherapy and in some cases radiotherapy. Optimal modalities of neo- or adjuvant treatments can be challenging taking into account potential long-term toxicities in this young population. This paper presents the recommendations for diagnosis and treatment of children and adolescents with PPB elaborated by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the European Union-funded project PARTNER (Paediatric Rare Tumours Network - European Registry).

Adjuvant therapy of histopathological risk factors of retinoblastoma in Europe: A survey by the European Retinoblastoma Group (EURbG).

INTRODUCTION: Advanced intraocular retinoblastoma can be cured by enucleation, but spread of retinoblastoma cells beyond the natural limits of the eye is related to a high mortality. Adjuvant therapy after enucleation has been shown to prevent metastasis in children with risk factors for extraocular retinoblastoma. However, histological criteria and adjuvant treatment regimens vary and there is no unifying consensus on the optimal choice of treatment. METHOD: Data on guidelines for adjuvant treatment in European retinoblastoma referral centres were collected in an online survey among all members of the European Retinoblastoma Group (EURbG) network. Extended information was gathered via personal email communication. RESULTS: Data were collected from 26 centres in 17 countries. Guidelines for adjuvant treatment were in place at 92.3% of retinoblastoma centres. There was a consensus on indication for and intensity of adjuvant treatment among more than 80% of all centres. The majority of centres use no adjuvant treatment for isolated focal choroidal invasion or prelaminar optic nerve invasion. Patients with massive choroidal invasion or postlaminar optic nerve invasion receive adjuvant chemotherapy, while microscopic invasion of the resection margin of the optic nerve or extension through the sclera are treated with combined chemo- and radiotherapy. CONCLUSION: Indications and adjuvant treatment regimens in European retinoblastoma referral centres are similar but not uniform. Further biomarkers in addition to histopathological risk factors could improve treatment stratification. The high consensus in European centres is an excellent foundation for a common European study with prospective validation of new biomarkers.

Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis.

Isolated neuroinflammatory disease has been described in case reports of familial hemophagocytic lymphohistiocytosis (FHL), but the clinical spectrum of disease manifestations, response to therapy and prognosis remain poorly defined. We combined an international survey with a literature search to identify FHL patients with (i) initial presentation with isolated neurological symptoms; (ii) absence of cytopenia and splenomegaly at presentation; and (iii) systemic HLH features no earlier than 3 months after neurological presentation. Thirty-eight (20 unreported) patients were identified with initial diagnoses including acute demyelinating encephalopathy, leukoencephalopathy, CNS vasculitis, multiple sclerosis, and encephalitis. Median age at presentation was 6.5 years, most commonly with ataxia/gait disturbance (75%) and seizures (53%). Diffuse multifocal white matter changes (79%) and cerebellar involvement (61%) were common MRI findings. CSF cell count and protein were increased in 22/29 and 15/29 patients, respectively. Fourteen patients progressed to systemic inflammatory disease fulfilling HLH-2004 criteria at a mean of 36.9 months after initial neurological presentation. Mutations were detected in PRF1 in 23 patients (61%), RAB27A in 10 (26%), UNC13D in 3 (8%), LYST in 1 (3%), and STXBP2 in 1 (3%) with a mean interval to diagnosis of 28.3 months. Among 19 patients who underwent HSCT, 11 neurologically improved, 4 were stable, one relapsed, and 3 died. Among 14 non-transplanted patients, only 3 improved or had stable disease, one relapsed, and 10 died. Isolated CNS-HLH is a rare and often overlooked cause of inflammatory brain disease. HLH-directed therapy followed by HSCT seems to improve survival and outcome.

Pediatric transplantation in Europe during the COVID-19 pandemic: Early impact on activity and healthcare.

The current pandemic SARS-CoV-2 has required an unusual allocation of resources that can negatively impact chronically ill patients and high-complexity procedures. Across the European Reference Network on Pediatric Transplantation (ERN TransplantChild), we conducted a survey to investigate the impact of the COVID-19 outbreak on pediatric transplant activity and healthcare practices in both solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT). The replies of 30 professionals from 18 centers in Europe were collected. Twelve of 18 centers (67%) showed a reduction in their usual transplant activity. Additionally, outpatient visits have been modified and restricted to selected ones, and the use of telemedicine tools has increased. Additionally, a total of 14 COVID-19 pediatric transplanted patients were identified at the time of the survey, including eight transplant recipients and six candidates for transplantation. Only two moderate-severe cases were reported, both in HSCT setting. These survey results demonstrate the limitations in healthcare resources for pediatric transplantation patients during early stages of this pandemic. COVID-19 disease is a major worldwide challenge for the field of pediatric transplantation, where there will be a need for systematic data collection, encouraging regular discussions to address the long-term consequences for pediatric transplantation candidates, recipients, and their families.

Early Radiation-Induced Sarcoma in an Adolescent Treated for Relapsed Hodgkin Lymphoma with Nivolumab.

Radiation-induced sarcoma (RIS) has been reported as a late secondary malignancy following radiotherapy for various types of cancer with a median latency of 10 years. We describe an early RIS that developed in an adolescent within three years of treatment (including PD-L1 check-point inhibitor Nivolumab) of a relapsed classic Hodgkin lymphoma (HL) and was diagnosed post-mortem. The patient died of the progressive RIS that was misleadingly assumed to be a resistant HL based on the positive PET/CT scan. Repetitive tumor biopsies are warranted in cases of aggressive and multi-drug resistant HL to validate imaging findings, ensure correct diagnosis and avoid overtreatment.

Low burden of minimal residual disease prior to transplantation in children with very high risk acute lymphoblastic leukaemia: The NOPHO ALL2008 experience.

The population-based Nordic/Baltic acute lymphoblastic leukaemia (ALL) Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol combined minimal residual disease (MRD)-driven treatment stratification with very intense first line chemotherapy for patients with high risk ALL. Patients with MRD ≥5% at end of induction or ≥10-3 at end of consolidation or following two high risk blocks were eligible for haematopoietic cell transplantation (HCT) in first remission. After at least three high risk blocks a total of 71 children received HCT, of which 46 had MRD ≥5% at end of induction. Ten patients stratified to HCT were not transplanted; 12 received HCT without protocol indication. Among 69 patients with evaluable pre-HCT MRD results, 22 were MRD-positive, one with MRD ≥10-3 . After a median follow-up of 5·5 years, the cumulative incidence of relapse was 23·5% (95% confidence interval [CI]: 10·5-47·7) for MRD-positive versus 5·1% (95% CI: 1·3-19·2), P = 0·02) for MRD-negative patients. MRD was the only variable significantly associated with relapse (hazard ratio 9·1, 95% CI: 1·6-51·0, P = 0·012). Non-relapse mortality did not differ between the two groups, resulting in disease-free survival of 85·6% (95% CI: 75·4-97·2) and 67·4% (95% CI: 50·2-90·5), respectively. In conclusion, NOPHO block treatment efficiently reduced residual leukaemia which, combined with modern transplant procedures, provided high survival rates, also among pre-HCT MRD-positive patients.

Antimicrobial Resistance in Gram-Negative Rods Causing Bacteremia in Hematopoietic Stem Cell Transplant Recipients: Intercontinental Prospective Study of the Infectious Diseases Working Party of the European Bone Marrow Transplantation Group.

BACKGROUND: This intercontinental study aimed to study gram-negative rod (GNR) resistance in hematopoietic stem cell transplantation (HSCT). METHODS: GNR bacteremias occurring during 6 months post-HSCT (February 2014-May 2015) were prospectively collected, and analyzed for rates and risk factors for resistance to fluoroquinolones, noncarbapenem anti-Pseudomonas ß-lactams (noncarbapenems), carbapenems, and multidrug resistance. RESULTS: Sixty-five HSCT centers from 25 countries in Europe, Australia, and Asia reported data on 655 GNR episodes and 704 pathogens in 591 patients (Enterobacteriaceae, 73%; nonfermentative rods, 24%; and 3% others). Half of GNRs were fluoroquinolone and noncarbapenem resistant; 18.5% carbapenem resistant; 35.2% multidrug resistant. The total resistance rates were higher in allogeneic HSCT (allo-HSCT) vs autologous HSCT (auto-HSCT) patients (P < .001) but similar in community-acquired infections. Noncarbapenem resistance and multidrug resistance were higher in auto-HSCT patients in centers providing vs not providing fluoroquinolone prophylaxis (P < .01). Resistance rates were higher in southeast vs northwest Europe and similar in children and adults, excluding higher fluoroquinolone- and ß-lactam/ß-lactamase inhibitor resistance rates in allo-HSCT adults. Non-Klebsiella Enterobacteriaceae were rarely carbapenem resistant. Multivariable analysis revealed resistance risk factors in allo-HSCT patients: fluoroquinolone resistance: adult, prolonged neutropenia, breakthrough on fluoroquinolones; noncarbapenem resistance: hospital-acquired infection, breakthrough on noncarbapenems or other antibiotics (excluding fluoroquinolones, noncarbapenems, carbapenems), donor type; carbapenem resistance: breakthrough on carbapenem, longer hospitalization, intensive care unit, previous other antibiotic therapy; multidrug resistance: longer hospitalization, breakthrough on ß-lactam/ß-lactamase inhibitors, and carbapenems. Inappropriate empiric therapy and mortality were significantly more common in infections caused by resistant bacteria. CONCLUSIONS: Our data question the recommendation for fluoroquinolone prophylaxis and call for reassessment of local empiric antibiotic protocols. Knowledge of pathogen-specific resistance enables early appropriate empiric therapy. Monitoring of resistance is crucial. CLINICAL TRIALS REGISTRATION: NCT02257931.

Improved outcome of childhood acute myeloid leukemia in an Eastern European country: Lithuanian experience.

The reported treatment outcomes of children treated for cancer in Eastern European countries are inferior to those in Northern/Western Europe. We hypothesized that recent survival rates could be comparable to the current standards and performed a population-based analysis of treatment outcome of childhood acute myeloid leukemia (AML) in Lithuania, a small Eastern European country. Children < 18 years old who were treated for AML from 2000 to 2013 were included (n = 54). Estimates of 5-year event-free (EFS5y) and overall survival (OS5y) rates were analyzed. Comparing periods 2000-2006 (n = 32) and 2007-2013 (n = 22), the EFS5y improved from 31 to 63% (p = 0.04), and the OS5y improved from 31 to 72% (p = 0.02) because of reductions in toxicity-related mortality (42 vs. 15%, p = 0.08) and relapse (43 vs. 25%, p = 0.08). The most significant improvement was demonstrated in high-risk patients (OS5y improved from 26 to 75%, p = 0.02) who benefited from hematopoietic stem cell transplantation: the post-transplant EFS5y increased from 13 to 86% (p = 0.01). CONCLUSIONS: The current survival rate of Lithuanian children treated for AML was comparable to the expected rate in other parts of Europe. What is Known: • In the last three decades, significant improvement has been achieved in treating childhood cancer, with an overall survival (OS) rate of > 80% in high-income countries. The difference in survival rates between Northern/Western and Eastern European countries as well as between high- and middle-/low-income countries is as much as 20%. Recently, the 5-year event-free survival rate of acute myeloid leukemia (AML) has reached > 60% in high-income countries. The survival rates for myeloproliferative diseases were the lowest in Eastern European countries. • The reported inferior survival rates were calculated based on outcome data of patients treated until 2007. The recent survival rates in Eastern European countries are unknown. What is New: • Being a small Eastern European country, Lithuania has experienced good economic growth during the last decade. We hypothesized that economic growth and gain of experience could result in better survival rates of children treated for cancer in our country in recent years. • A population-based analysis of treatment outcome of childhood AML treated in Lithuania in the recent years was performed for the first time. The survival rates of childhood AML in Lithuania are comparable to those of other high-income countries. Current survival rates of children treated for cancer in Eastern European countries could be comparable to the best current standards contributing to better European survival rates of childhood cancer in general.

Intravesical cidofovir to treat BK virus-associated hemorrhagic cystitis in children after hematopoietic stem cell transplantation.

HC related to BK virus replication might be a severe complication following allogeneic HSCT. There are no clearly defined treatment guidelines in pediatric population. The data on the effectiveness of ICI to manage severe bleeding in children are very limited. We report our experience of intravesical cidofovir in four children, 6-15 yr of age, to manage grade III-IV BK virus-associated HC. Three of four children had high CSA serum level prior to developing cystitis. Intravesical instillations of cidofovir resulted only in temporal relief of bleeding. After immune suppression was withdrawn or tapered, intravesical instillations of formalin solution had to be undertaken to abort severe bleeding. We concluded that intravesical cidofovir alone did not appear to be sufficiently effective in case of severe HC, necessitating complimentary procedures to stop macrohematuria.

Risk of complications during hematopoietic stem cell collection in pediatric sibling donors: a prospective European Group for Blood and Marrow Transplantation Pediatric Diseases Working Party study.

We investigated prospectively factors influencing the safety of hematopoietic stem cell (HSC) collection in 453 pediatric donors. The children in the study donated either BM or peripheral blood stem cells (PBSCs) according to center policy. A large variability in approach to donor issues was observed between the participating centers. Significant differences were observed between BM and PBSC donors regarding pain, blood allotransfusion, duration of hospital stay, and iron supplementation; however, differences between the groups undergoing BM vs PBSC donation preclude direct risk comparisons between the 2 procedures. The most common adverse event was pain, reported mainly by older children after BM harvest, but also observed after central venous catheter (CVC) placement for PBSC collection. With regard to severe adverse events, one patient (0.7%) developed a pneumothorax with hydrothorax after CVC placement for PBSC collection. The risk of allotransfusion after BM harvest was associated with a donor age of < 4 years and a BM harvest volume of > 20 mL/kg. Children < 4 years were at higher risk than older children for allotransfusion after BM harvest and there was a higher risk of complications from CVC placement before apheresis. We conclude that PBSC and BM collection are safe procedures in children.

An assessment of iron overload in children treated for cancer and nonmalignant hematologic disorders.

UNLABELLED: Our goal was to assess the natural fate of iron overload (IO) following transfusions of packed red blood cells (PRBCs) in children treated for cancer and nonmalignant disorders according to the intensity level of their treatment. Sixty-six children were followed up from February 2010 to March 2013. The transfusion burden was compared between three treatment intensity groups assigned according to the Intensity of Treatment Rating Scale 3.0 (ITR-3). IO was assessed by serial measurements of serum ferritin (SF) (n= 66) and quantification of tissue iron by magnetic resonance imaging (MRI) (n=12). Of the children studied, 36 % (24/66) received moderately intensive treatment (level 2), 21 % (14/ 66) received very intensive treatment (level 3), and 42 % (28/ 66) received the most intensive treatment (level 4). The number of PRBC (p=0.016), the total transfused volume (p= 0.026), and transfused volume adjusted to body weight (p= 0.004) were significantly higher in the level 4 group. By the median follow-up time of 35.5 months (range 8­133), 21­ 29 % of patients (including level 2 and level 3 children) had SF >1,000 µg/l 1 year after cessation of transfusions. The slowest decrease of SF was observed in the level 4 group. Initial MRI examination demonstrated either mild or moderate IO in the liver and spleen. Repetitive MRI showed significant improvement in relaxation time between the initial and follow-up MRI performances in the liver (5.9 vs. 8.6 ms, p= 0.03) and the spleen (4.3 vs. 8.8 ms, p=0.03). CONCLUSION: IO diminished over time, but in the level 4 patients, it was detectable for years after cessation of transfusions.