Publications by authors named "Luciano Dalla Pozza"

54 Publications

Factors That Influence Use of a Patient Portal by Health Professionals.

Int J Environ Res Public Health 2021 Feb 15;18(4). Epub 2021 Feb 15.

Research in Implementation Science and eHealth Group (RISe), Faculty of Medicine and Health, The University of Sydney, Sydney 2006, Australia.

Patient portals are websites or apps that provide patients with tools to manage healthcare appointments, access their health records, and communicate with clinicians. Patient portals have been demonstrated to be beneficial for improving communication between patients/carers and their healthcare team in a range of health settings. However, there is limited research on the barriers and enablers for implementing patient portals from the perspective of health professionals and healthcare teams, particularly in a paediatric setting. This study aimed to understand healthcare teams' experiences of using a patient portal and, using the Unified Theory of Acceptance and Use of Technology (UTAUT) framework, explore the barriers and enablers to ongoing use. Participants were 11 health professionals participating in the pilot of a patient portal for patients/carers in paediatric care. Data were collected using semi-structured interviews. Analysis of the interview data identified nine themes about implementing a patient portal in paediatric care, all of which aligned with the four constructs of the UTAUT. This study identified that barriers and enablers of the uptake of a patient portal by health professionals in a paediatric context aligned with the UTAUT framework. Value for the patient, improved workflow, and adequate technical and implementation support were highlighted by participants.
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http://dx.doi.org/10.3390/ijerph18041877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919023PMC
February 2021

Outcomes for Australian children with relapsed/refractory acute lymphoblastic leukaemia treated with blinatumomab.

Pediatr Blood Cancer 2021 May 26;68(5):e28922. Epub 2021 Feb 26.

Department of Clinical Haematology, Oncology and Bone Marrow Transplantation, Perth Children's Hospital, Perth, Western Australia, Australia.

We report on the Australian experience of blinatumomab for treatment of 24 children with relapsed/refractory precursor B-cell acute lymphoblastic leukaemia (B-ALL) and high-risk genetics, resulting in a minimal residual disease (MRD) response rate of 58%, 2-year progression-free survival (PFS) of 39% and 2-year overall survival of 63%. In total, 83% (n = 20/24) proceeded to haematopoietic stem cell transplant, directly after blinatumomab (n = 12) or following additional salvage therapy (n = 8). Four patients successfully received CD19-directed chimeric antigen receptor T-cell therapy despite prior blinatumomab exposure. Inferior 2-year PFS was associated with MRD positivity (20%, n = 15) and in KMT2A-rearranged infants (15%, n = 9). Our findings highlight that not all children with relapsed/refractory B-ALL respond to blinatumomab and factors such as blast genotype may affect prognosis.
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http://dx.doi.org/10.1002/pbc.28922DOI Listing
May 2021

CKLF and IL1B transcript levels at diagnosis are predictive of relapse in children with pre-B-cell acute lymphoblastic leukaemia.

Br J Haematol 2021 Apr 23;193(1):171-175. Epub 2021 Feb 23.

Adelaide Medical School, Faculty of Health and Medical Science, University of Adelaide, Adelaide, SA, Australia.

Disease relapse is the greatest cause of treatment failure in paediatric B-cell acute lymphoblastic leukaemia (B-ALL). Current risk stratifications fail to capture all patients at risk of relapse. Herein, we used a machine-learning approach to identify B-ALL blast-secreted factors that are associated with poor survival outcomes. Using this approach, we identified a two-gene expression signature (CKLF and IL1B) that allowed identification of high-risk patients at diagnosis. This two-gene expression signature enhances the predictive value of current at diagnosis or end-of-induction risk stratification suggesting the model can be applied continuously to help guide implementation of risk-adapted therapies.
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http://dx.doi.org/10.1111/bjh.17161DOI Listing
April 2021

Methotrexate-related central neurotoxicity: clinical characteristics, risk factors and genome-wide association study in children treated for acute lymphoblastic leukemia.

Haematologica 2021 Feb 11. Epub 2021 Feb 11.

Kids Cancer Centre, Sydney Children's Hospital Randwick, Sydney, Australia; School of Women and Children's Health, University of New South Wales (UNSW), Sydney, Australia; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW, Sydney.

Symptomatic methotrexate-related central neurotoxicity, 'MTX neurotoxicity', is a severe toxicity experienced during acute lymphoblastic leukemia (ALL) therapy with potential long-term neurologic complications. Risk factors and long-term outcomes require further study. We conducted a systematic, retrospective review of 1251 consecutive Australian children enrolled on BFM or COG-based protocols between 1998-2013. Clinical risk predictors for MTX neurotoxicity were analyzed using regression. A genome-wide association study (GWAS) was performed on 48 cases and 537 controls. The incidence of MTX neurotoxicity was 7.6% (n=95/1251), at a median of 4 months from ALL diagnosis and 8 days after intravenous or intrathecal MTX. Grade 3 elevation of serum aspartate aminotransferase (P=0.005, OR 2.31 (1.28-4.16)) in induction/consolidation was associated with MTX neurotoxicity, after accounting for the only established risk factor, age a10 years. Cumulative incidence of CNS relapse was increased in children where intrathecal MTX was omitted following symptomatic MTX neurotoxicity (n=48) compared to where intrathecal MTX was continued throughout therapy (n=1174) (P=0.047). Five-year CNS relapsefree survival was 89.2%±4.6% when intrathecal MTX was ceased compared to 95.4%±0.6% when intrathecal MTX was continued. Recurrence of MTX neurotoxicity was low (12.9%) for patients whose intrathecal MTX was continued after their first episode. The GWAS identified SNPs associated with MTX neurotoxicity near genes regulating neuronal growth, neuronal differentiation and cytoskeletal organization (P>1E-06). In conclusion, increased serum aspartate aminotransferase and age a10 years at diagnosis were independent risk factors for MTX neurotoxicity. Our data do not support cessation of intrathecal MTX after a first MTX neurotoxicity event.
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http://dx.doi.org/10.3324/haematol.2020.268565DOI Listing
February 2021

Inotuzumab ozogamicin in infants and young children with relapsed or refractory acute lymphoblastic leukaemia: a case series.

Br J Haematol 2021 Feb 2. Epub 2021 Feb 2.

Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.

No data on inotuzumab ozogamicin (InO) in infant acute lymphoblastic leukaemia (ALL) have been published to date. We collected data internationally on infants/young children (<3 years) with ALL treated with InO. Fifteen patients (median 4.4 months at diagnosis) received InO due to relapsed or refractory (R/R) disease. Median percentage of CD22 blasts was 72% (range 40-100%, n = 9). The median dose in the first course was 1.74 mg/m (fractionated). Seven patients (47%) achieved complete remission; one additional minimal residual disease (MRD)-positive patient became MRD-negative. Six-month overall survival was 47% (95% confidence interval [CI] 27-80%). Two patients developed veno-occlusive disease after transplant. Further evaluation of InO in this subgroup of ALL is justified.
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http://dx.doi.org/10.1111/bjh.17333DOI Listing
February 2021

Outcomes of paediatric patients with B-cell acute lymphocytic leukaemia with ABL-class fusion in the pre-tyrosine-kinase inhibitor era: a multicentre, retrospective, cohort study.

Lancet Haematol 2021 Jan 22;8(1):e55-e66. Epub 2020 Dec 22.

Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands. Electronic address:

Background: ABL-class fusion genes other than BCR-ABL1 have been identified in approximately 3% of children with newly diagnosed acute lymphocytic leukaemia, and studies suggest that leukaemic cells carrying ABL-class fusions can be targeted successfully by tyrosine-kinase inhibitors. We aimed to establish the baseline characteristics and outcomes of paediatric patients with ABL-class fusion B-cell acute lymphocytic leukaemia in the pre-tyrosine-kinase inhibitor era.

Methods: This multicentre, retrospective, cohort study included paediatric patients (aged 1-18 years) with newly diagnosed ABL-class fusion (ABL1 fusion-positive, ABL2 fusion-positive, CSF1R fusion-positive, and PDGFRB fusion-positive) B-cell acute lymphocytic leukaemia enrolled in clinical trials of multidrug chemotherapy done between Oct 3, 2000, and Aug 28, 2018, in which tyrosine-kinase inhibitors had not been given as a first-line treatment. Patients from 14 European, North American, and Asia-Pacific study groups of the Ponte di Legno group were included. No patients were excluded, and patients were followed up by individual study groups. Through the Ponte di Legno group, we collected data on the baseline characteristics of patients, including IKZF1, PAX5, and CDKN2A/B deletion status, and whether haematopoietic stem cell transplantation (HSCT) had been done, as well as treatment outcomes, including complete remission, no response, relapse, early death, and treatment-related mortality, response to prednisone, and minimal residual disease (MRD) at end of induction therapy. 5-year event-free survival and 5-year overall survival were estimated by use of Kaplan-Meier methods, and the 5-year cumulative incidence of relapse was calculated by use of a competing risk model.

Findings: We identified 122 paediatric patients with newly diagnosed ABL-class fusion B-cell acute lymphocytic leukaemia (77 from European study groups, 25 from North American study groups, and 20 from Asia-Pacific study groups). 64 (52%) of 122 patients were PDGFRB fusion-positive, 40 (33%) were ABL1 fusion-positive, ten (8%) were CSF1R fusion-positive, and eight (7%) were ABL2 fusion-positive. In all 122 patients, 5-year event-free survival was 59·1% (95% CI 50·5-69·1), 5-year overall survival was 76·1% (68·6-84·5), and the 5-year cumulative incidence of relapse was 31·0% (95% CI 22·4-40·1). MRD at the end of induction therapy was high (≥10 cells) in 61 (66%) of 93 patients, and most prevalent in patients with ABL2 fusions (six [86%] of 7 patients) and PDGFRB fusion-positive B-cell acute lymphocytic leukaemia (43 [88%] of 49 patients). MRD at the end of induction therapy of 10 cells or more was predictive of an unfavourable outcome (hazard ratio of event-free survival in patients with a MRD of ≥10vs those with a MRD of <10 3·33 [95% CI 1·46-7·56], p=0·0039). Of the 36 (30%) of 119 patients who relapsed, 25 (69%) relapsed within 3 years of diagnosis. The 5-year cumulative incidence of relapse in 41 patients who underwent HSCT (17·8% [95% CI 7·7-31·3]) was lower than in the 43 patients who did not undergo HSCT (45·1% [28·4-60·5], p=0·013), but event-free survival and overall survival did not differ between these two groups.

Interpretation: Children with ABL-class fusion B-cell acute lymphocytic leukaemia have poor outcomes when treated with regimens that do not contain a tyrosine-kinase inhibitor, despite the use of high-risk chemotherapy regimens and frequent HSCT upon first remission. Our findings provide a reference for evaluating the potential benefit of first-line tyrosine-kinase inhibitor treatment in patients with ABL-class fusion B-cell acute lymphocytic leukaemia.

Funding: The Oncode Institute, Pediatric Cancer Foundation Rotterdam, Dutch Cancer Society, Kika Foundation, Deutsche Krebshilfe, Blood Cancer UK, Associazione Italiana per la Ricerca sul Cancro, Cancer Australia, National Cancer Institute, National Institute of Health, and St Baldrick's Foundation.
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http://dx.doi.org/10.1016/S2352-3026(20)30353-7DOI Listing
January 2021

Whole genome, transcriptome and methylome profiling enhances actionable target discovery in high-risk pediatric cancer.

Nat Med 2020 11 5;26(11):1742-1753. Epub 2020 Oct 5.

Children's Cancer Institute, Lowy Cancer Centre, UNSW Sydney, Kensington, NSW, Australia.

The Zero Childhood Cancer Program is a precision medicine program to benefit children with poor-outcome, rare, relapsed or refractory cancer. Using tumor and germline whole genome sequencing (WGS) and RNA sequencing (RNAseq) across 252 tumors from high-risk pediatric patients with cancer, we identified 968 reportable molecular aberrations (39.9% in WGS and RNAseq, 35.1% in WGS only and 25.0% in RNAseq only). Of these patients, 93.7% had at least one germline or somatic aberration, 71.4% had therapeutic targets and 5.2% had a change in diagnosis. WGS identified pathogenic cancer-predisposing variants in 16.2% of patients. In 76 central nervous system tumors, methylome analysis confirmed diagnosis in 71.1% of patients and contributed to a change of diagnosis in two patients (2.6%). To date, 43 patients have received a recommended therapy, 38 of whom could be evaluated, with 31% showing objective evidence of clinical benefit. Comprehensive molecular profiling resolved the molecular basis of virtually all high-risk cancers, leading to clinical benefit in some patients.
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http://dx.doi.org/10.1038/s41591-020-1072-4DOI Listing
November 2020

Electronic ordering and the management of treatment interdependencies: a qualitative study of paediatric chemotherapy.

BMC Med Inform Decis Mak 2020 08 14;20(1):193. Epub 2020 Aug 14.

Australian Institute of Health Innovation, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, Australia.

Background: There are serious safety risks associated with chemotherapy, often associated with interdependencies in regimens administered over months or years. Various strategies are used to manage these risks. Computerized provider order entry (CPOE) systems are also implemented to improve medication safety. Little is known regarding the effect of CPOE on how clinicians manage chemotherapy interdependencies and their associated safety strategies.

Methods: We conducted a multi-method qualitative study in a paediatric hospital. We analysed 827 oncology incidents reported following CPOE implementation and carried out semi-structured interviews with doctors (n = 10), nurses (n = 6), a pharmacist, and oncology CPOE team members (n = 2). Results were interpreted according to safety models (ultra-safe, high-reliability organisations [HROs], or ultra-adaptive).

Results: Incident reports highlighted two interrelated types of interdependencies: those within organisation of clinical activities and those inherent in chemotherapy regimens. Clinicians reported strategies to address chemotherapy risks and interdependencies. These included rigid rules and 'no go' contexts for treatment to proceed, typical of the ultra-safe model; use of time (e.g. planning only so far ahead) and sensitivity to operations, typical of HROs. We identified three different time horizons in CPOE use in relation to patients' treatments: life-long, the whole regimen, and the 'here and now'. CPOE supported ultra-safe strategies through automation and access to rules/standardisation, but also created difficulties and contributed to incidents. It supported the 'here and now' better than a life-long or whole regimen view of a patient treatment. Sensitivity to operations was essential to anticipate and resolve uncertainties, hazards, CPOE limitations, and mismatches between CPOE processes and workflow in practice.

Conclusions: Within oncology, CPOE appears to move the 'mix' of risk strategies towards ultra-safe models of safety and protocol-mandated care. However, in order to operate ultra-safe strategies embedded in CPOE and stay on protocol it is essential for clinicians to be thoughtful and show sensitivity to operations in CPOE use. CPOE design can be advanced by better consideration of mechanisms to support interdependencies.
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http://dx.doi.org/10.1186/s12911-020-01212-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427723PMC
August 2020

Associations between double-checking and medication administration errors: a direct observational study of paediatric inpatients.

BMJ Qual Saf 2021 Apr 7;30(4):320-330. Epub 2020 Aug 7.

Centre for Health Systems and Safety Research, Australian Institute of Health Innovation, Macquarie University, Sydney, New South Wales, Australia.

Background: Double-checking the administration of medications has been standard practice in paediatric hospitals around the world for decades. While the practice is widespread, evidence of its effectiveness in reducing errors or harm is scarce.

Objectives: To measure the association between double-checking, and the occurrence and potential severity of medication administration errors (MAEs); check duration; and factors associated with double-checking adherence.

Methods: Direct observational study of 298 nurses, administering 5140 medication doses to 1523 patients, across nine wards, in a paediatric hospital. Independent observers recorded details of administrations and double-checking (independent; primed-one nurse shares information which may influence the checking nurse; incomplete; or none) in real time during weekdays and weekends between 07:00 and 22:00. Observational medication data were compared with patients' medical records by a reviewer (blinded to checking-status), to identify MAEs. MAEs were rated for potential severity. Observations included administrations where double-checking was mandated, or optional. Multivariable regression examined the association between double-checking, MAEs and potential severity; and factors associated with policy adherence.

Results: For 3563 administrations double-checking was mandated. Of these, 36 (1·0%) received independent double-checks, 3296 (92·5%) primed and 231 (6·5%) no/incomplete double-checks. For 1577 administrations double-checking was not mandatory, but in 26·3% (n=416) nurses chose to double-check. Where double-checking was mandated there was no significant association between double-checking and MAEs (OR 0·89 (0·65-1·21); p=0·44), or potential MAE severity (OR 0·86 (0·65-1·15); p=0·31). Where double-checking was not mandated, but performed, MAEs were less likely to occur (OR 0·71 (0·54-0·95); p=0·02) and had lower potential severity (OR 0·75 (0·57-0·99); p=0·04). Each double-check took an average of 6·4 min (107 hours/1000 administrations).

Conclusions: Compliance with mandated double-checking was very high, but rarely independent. Primed double-checking was highly prevalent but compared with single-checking conferred no benefit in terms of reduced errors or severity. Our findings raise questions about if, when and how double-checking policies deliver safety benefits and warrant the considerable resource investments required in modern clinical settings.
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http://dx.doi.org/10.1136/bmjqs-2020-011473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982937PMC
April 2021

The efficiency-thoroughness trade-off after implementation of electronic medication management: a qualitative study in paediatric oncology.

Int J Qual Health Care 2020 Nov;32(8):511-516

Centre for Health Systems & Safety Research, Australian Institute of Health Innovation, Macquarie University, Sydney, Australia.

Objective: The efficiency-thoroughness trade-off (ETTO) principle proposes that people and organizations are often required to make a trade-off between being efficient and being thorough, as it is difficult to be both efficient and thorough at the same time. This study aimed to compare pre- electronic medication management system (EMMS) expectation of how an EMMS is likely to impact on efficiency and thoroughness to post-EMM experiences of an EMMS and the ETTO.

Design: Qualitative interview study.

Setting: A paediatric oncology cancer centre in a large paediatric tertiary teaching hospital in Sydney, Australia.

Participants: Forty-four semi-structured interviews with doctors, nurses and pharmacists six months prior to and two years following implementation of an EMMS.

Results: Prior to EMM implementation, staff identified a number of areas of work where both efficiency and thoroughness were expected to improve with EMM. These included ease of accessibility of the medication record, and organization and legibility of medication information. Following EMMS implementation, staff reported improvements in these areas. However, the EMMS was perceived to drive thoroughness (safety) benefits at the expense of efficiency (time). Measures to improve safety in the EMMS enforced processes that required time, such as medication double-checking procedures.

Conclusions: Overall, staff were aware of the competitive interplay between thoroughness and efficiency and reported that introduction of an EMMS had imposed processes that favoured improvements in thoroughness at the expense of efficiency.
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http://dx.doi.org/10.1093/intqhc/mzaa086DOI Listing
November 2020

Genome-Wide Association Meta-Analysis of Single-Nucleotide Polymorphisms and Symptomatic Venous Thromboembolism during Therapy for Acute Lymphoblastic Leukemia and Lymphoma in Caucasian Children.

Cancers (Basel) 2020 May 19;12(5). Epub 2020 May 19.

Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, 2100 Copenhagen, Denmark.

Symptomatic venous thromboembolism (VTE) occurs in five percent of children treated for acute lymphoblastic leukemia (ALL), but whether a genetic predisposition exists across different ALL treatment regimens has not been well studied.

Methods: We undertook a genome-wide association study (GWAS) meta-analysis for VTE in consecutively treated children in the Nordic/Baltic acute lymphoblastic leukemia 2008 (ALL2008) cohort and the Australian Evaluation of Risk of ALL Treatment-Related Side-Effects (ERASE) cohort. A total of 92 cases and 1481 controls of European ancestry were included.

Results: No SNPs reached genome-wide significance ( < 5 × 10) in either cohort. Among the top 34 single-nucleotide polymorphisms (SNPs) ( < 1 × 10), two loci had concordant effects in both cohorts: (rs1804772) (MAF: 1%; = 3.95 × 10) that influences arachidonic acid metabolism and thus platelet aggregation, and (rs570684) (MAF: 1%; = 4.34 × 10) that has been previously associated with risk of ischemic stroke, atherosclerosis, and early-onset coronary artery disease.

Conclusion: This represents the largest GWAS meta-analysis conducted to date associating SNPs to VTE in children and adolescents treated on childhood ALL protocols. Validation of these findings is needed and may then lead to patient stratification for VTE preventive interventions. As VTE hemostasis involves multiple pathways, a more powerful GWAS is needed to detect combination of variants associated with VTE.
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http://dx.doi.org/10.3390/cancers12051285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280960PMC
May 2020

Results from an international phase 2 study of the anti-CD22 immunotoxin moxetumomab pasudotox in relapsed or refractory childhood B-lineage acute lymphoblastic leukemia.

Pediatr Blood Cancer 2020 05 15;67(5):e28112. Epub 2020 Jan 15.

Children's Hospital Los Angeles, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California.

Background: In a multicenter phase 1 study of children with relapsed/refractory acute lymphoblastic leukemia (ALL), moxetumomab pasudotox, an anti-CD22 immunotoxin, demonstrated a manageable safety profile and preliminary evidence of clinical activity. A phase 2 study further evaluated efficacy.

Procedure: This international, multicenter, phase 2 study enrolled children with relapsed/refractory B-cell precursor ALL who received moxetumomab pasudotox 40 µg/kg intravenously every other day, for six doses per 21-day cycle. The primary objective was to evaluate the complete response (CR) rate. Secondary objectives included safety, pharmacokinetics, and immunogenicity evaluations.

Results: Thirty-two patients (median age, 10 years) were enrolled at 16 sites; 30 received study drug and were evaluable for safety; 28 were evaluable for response. The objective response rate was 28.6%, with three patients (10.7%) achieving morphologic CR, and five patients (17.9%) achieving partial response. Disease progression occurred in 11 patients (39.3%). Ten patients (33.3%) experienced at least one treatment-related serious adverse event, including capillary leak syndrome (CLS; n = 6), hemolytic uremic syndrome (HUS; n = 4), and treatment-related death (n = 1) from pulmonary edema. No differences were observed in inflammatory markers in patients who did or did not develop CLS or HUS.

Conclusions: Despite a signal for clinical activity, this phase 2 study was terminated at interim analysis for a CR rate that did not reach the stage 1 target. Preclinical data suggest enhanced efficacy of moxetumomab pasudotox via continuous infusion or in combination regimens; thus, further studies designed to optimize the efficacy and safety of moxetumomab pasudotox in pediatric ALL may be warranted.
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http://dx.doi.org/10.1002/pbc.28112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485266PMC
May 2020

Communication during childhood cancer: Systematic review of patient perspectives.

Cancer 2020 02 10;126(4):701-716. Epub 2019 Dec 10.

School of Public Health, University of Sydney, Sydney, New South Wales, Australia.

Effective communication is challenging in childhood cancer, where decisions carry unpredictable and life-threatening implications. We aimed to describe patients' experiences of communicating with clinicians during treatment of childhood cancer. A systematic review of qualitative studies to April 2019 was performed. Eligible studies included patients diagnosed with cancer at age ≤ 18 years and reported their perspectives of communicating with clinicians during treatment of childhood cancer. Data were extracted from primary studies for thematic synthesis. From 101 articles across 25 countries involving 1870 participants who were diagnosed with cancer between ages 3 to 18 years, we identified 6 themes: 1) rendered invisible and powerless (displaced and undermined by adult authority; betrayed and distrustful; feeling neglected; helpless and intimidated; disempowered by lack of information); 2) fear and worry for the future (paralyzed by devastating news; uncertainty, anticipation, and dread; broaching intimate and private topics); 3) burdened with responsibility (pressured and unprepared; balancing external expectations; protecting hope); 4) therapeutic patient-provider relationships (emotional support and encouragement; validated personhood and companionship); 5) safety in trust (truthfulness and transparency; prepared by awareness and understanding; reassured by reliable expertise; depending on adults for protection and difficult decisions; security in expressing opinions and needs); and 6) empowerment and assertive agency (right to individual knowledge and choice; control over own life; partnership and respect; enhancing capacity for self-management). During treatment of childhood cancer, patients gain a sense of respect, safety, and control when they feel clinicians address their information and developmental needs. However, communication that is perceived to be parent-centered can be disempowering. Promoting child agency and partnership may improve care and outcomes for children with cancer.
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http://dx.doi.org/10.1002/cncr.32637DOI Listing
February 2020

Medication safety incidents in paediatric oncology after electronic medication management system implementation.

Eur J Cancer Care (Engl) 2019 Nov 22;28(6):e13152. Epub 2019 Aug 22.

Centre for Health Systems and Safety Research, AIHI, Macquarie University, Sydney, NSW, Australia.

Objective: To explore medication safety issues related to use of an electronic medication management system (EMM) in paediatric oncology practice, through the analysis of patient safety incident reports.

Methods: We analysed 827 voluntarily reported incidents relating to oncology patients that occurred over an 18-month period immediately following implementation of an EMM in a paediatric hospital in Australia. We identified medication-related and EMM-related incidents and carried out a content analysis to identify patterns.

Results: We found ~79% (n = 651) of incidents were medication-related and, of these, ~45% (n = 294) were EMM-related. Medication-related incidents included issues with: prescribing; dispensing; administration; patient transfers; missing chemotherapy protocols and information on current stage of patient treatment; coordination of chemotherapy administration; handling or storing medications; children or families handling medications. EMM-related incidents were classified into four groups: technical issues, issues with the user experience, unanticipated problems in EMM workflow, and missing safety features.

Conclusions: Incidents reflected difficulties with managing therapies rich in interdependencies. EMM, and especially its 'automaticity', contributed to these incidents. As EMM impacts on safety in such high-risk settings, it is essential that users are aware of and attend to EMM automatic behaviours and are equipped to troubleshoot them.
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http://dx.doi.org/10.1111/ecc.13152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161912PMC
November 2019

Long-term morbidity of respiratory viral infections during chemotherapy in children with leukaemia.

Pediatr Pulmonol 2019 11 8;54(11):1821-1829. Epub 2019 Aug 8.

Department of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, Australia.

Background: Respiratory viruses are a common cause of infection in immunosuppressed children undergoing cancer therapy. Pulmonary sequelae have been documented following respiratory viral infections (RVIs) in hematopoietic stem cell transplant (HSCT) recipients; however potential late effects in children undergoing nonmyeloablative chemotherapy have not been investigated.

Aim: To evaluate the long-term pulmonary morbidity of respiratory viral infections during chemotherapy in children with acute lymphoblastic leukemia (ALL).

Methods: Childhood ALL survivors, aged 7 to 18 years, greater than 6 months posttreatment were recruited. Exclusion criteria included HSCT or proven bacterial/fungal respiratory infection during treatment. Subjects were classified into "viral" or "control" groups according to retrospective medical records that documented the presence of laboratory-proven RVIs during chemotherapy. Symptom questionnaires (Liverpool, ISAAC) and lung function testing (spirometry, plethysmography, diffusing capacity, forced oscillation technique to ATS/ERS standards) were then performed cross-sectionally at the time of recruitment.

Results: Fifty-four patients (31 viral, 23 control) were recruited: median (range) age 11.2 (7.2-18.1) years, and at 4.9 (0.5-13) years posttherapy. Abnormalities were detected in 17 (31%) individuals (8 viral, 9 control), with the most common being DLCO impairment (3 viral, 4 control) and reduced respiratory reactance at 5 Hz (5 viral, 6 control). Children with RVIs during chemotherapy reported more current respiratory symptoms, particularly wheeze (odds ratio [OR], 3.0; 95% confidence interval [CI]: 0.9-10.0; P = .09) and cough (OR, 2.7; 95% CI: 0.8-9.5; P = .11). No differences in lung function tests were observed between the two groups.

Conclusions: Our study found children with RVIs during chemotherapy developed more long-term respiratory symptoms than controls; however, differences did not reach statistical significance. No differences in static lung function were found between the two groups. Overall, pulmonary abnormalities and/or significant ongoing respiratory symptoms were detected in nearly a third of ALL survivors treated without HSCT. Larger, prospective studies are warranted to evaluate the etiology and clinical significance of these findings.
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http://dx.doi.org/10.1002/ppul.24456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167615PMC
November 2019

Correction: Inotuzumab ozogamicin in pediatric patients with relapsed/refractory acute lymphoblastic leukemia.

Leukemia 2019 Apr;33(4):1061-1062

Childrens Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA.

We thank the research coordinators and following physicians at pediatric cancer centers for contributing data to this project: Prashant Hiwarkar and Jayashree Motwani, Birmingham Women's and Children's Hospital, UK; Kelly Malone, Children's Hospital of Colorado, USA; Mylene Bassal, Children's Hospital of Eastern Ontario, Canada; Yoav Messinger and Joanna Perkins, Children's Hospital of Minnesota, USA; Van Huynh, Children's Hospital of Orange County, USA; Richard Ho, Children's Hospital at Vanderbilt, USA; Joanne Chuah and Jessa Morales, Children's Hospital at Westmead, Australia; Donald Wells, Dell Children's Hospital, USA; Nicolas Boissel, Hospital Saint-Louis, France; Tannie Huang, Kaiser Permanente, USA; Stacey Marjerrison, McMaster Children's Hospital, Canada; William Carroll and Joanna Pierro, New York University Langone Medical Center, USA; Ajay Vora, Sheffield Children's Hospital, UK; Donna Lancaster, The Royal Marsden Hospital, UK; Lucie Šrámková, University Hospital Motol, Czech Republic; Chatchawin Assanasen, University of Texas Health Science Center, San Antonio, USA; Rupert Handgretinger, University of Tübingen, Germany.
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http://dx.doi.org/10.1038/s41375-019-0426-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608412PMC
April 2019

Validation of the United Kingdom copy-number alteration classifier in 3239 children with B-cell precursor ALL.

Blood Adv 2019 01;3(2):148-157

Wolfson Childhood Cancer Research Centre, Northern Institute for Cancer Research, Newcastle University, Newcastle, United Kingdom.

Genetic abnormalities provide vital diagnostic and prognostic information in pediatric acute lymphoblastic leukemia (ALL) and are increasingly used to assign patients to risk groups. We recently proposed a novel classifier based on the copy-number alteration (CNA) profile of the 8 most commonly deleted genes in B-cell precursor ALL. This classifier defined 3 CNA subgroups in consecutive UK trials and was able to discriminate patients with intermediate-risk cytogenetics. In this study, we sought to validate the United Kingdom ALL (UKALL)-CNA classifier and reevaluate the interaction with cytogenetic risk groups using individual patient data from 3239 cases collected from 12 groups within the International BFM Study Group. The classifier was validated and defined 3 risk groups with distinct event-free survival (EFS) rates: good (88%), intermediate (76%), and poor (68%) ( < .001). There was no evidence of heterogeneity, even within trials that used minimal residual disease to guide therapy. By integrating CNA and cytogenetic data, we replicated our original key observation that patients with intermediate-risk cytogenetics can be stratified into 2 prognostic subgroups. Group A had an EFS rate of 86% (similar to patients with good-risk cytogenetics), while group B patients had a significantly inferior rate (73%, < .001). Finally, we revised the overall genetic classification by defining 4 risk groups with distinct EFS rates: very good (91%), good (81%), intermediate (73%), and poor (54%), < .001. In conclusion, the UKALL-CNA classifier is a robust prognostic tool that can be deployed in different trial settings and used to refine established cytogenetic risk groups.
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http://dx.doi.org/10.1182/bloodadvances.2018025718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341196PMC
January 2019

Investigation of clinically relevant germline variants detected by next-generation sequencing in patients with childhood cancer: a review of the literature.

J Med Genet 2018 12 4;55(12):785-793. Epub 2018 Oct 4.

Children's Cancer Research Unit, Kids Research and Discipline of Child and Adolescent Health, University of Sydney, Westmead, New South Wales, Australia.

Genetic predisposition is an important underlying cause of childhood cancer, although the proportion of patients with childhood cancer carrying predisposing pathogenic germline variants is uncertain. This review considers the pathogenic or likely pathogenic germline variants reported by six studies that used next-generation sequencing to investigate genetic predisposition in selected cohorts of patients with childhood cancer and used incompletely overlapping gene sets for analysis and interpretation. These six studies reported that 8.5%-35.5% of patients with childhood cancer carried clinically relevant germline variants. Analysis of 52 autosomal dominant cancer predisposition genes assumed common to all six studies showed that 5.5%-25.8% of patients with childhood cancer carried pathogenic or likely pathogenic germline variants in at least one of these genes. When only non-central nervous system solid tumours (excluding adrenocortical carcinomas) were considered, 8.5%-10.3% of the patients carried pathogenic or likely pathogenic germline variants in at least one of 52 autosomal dominant cancer predisposition genes. There was a lack of concordance between the genotype and phenotype in 33.3%-57.1% of the patients reported with pathogenic or likely pathogenic germline variants, most of which represented variants in autosomal dominant cancer predisposition genes associated with adult onset cancers. In summary, germline genetic testing in patients with childhood cancer requires clear definition of phenotypes and genes considered for interpretation, with potential to inform and broaden childhood cancer predisposition syndromes.
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http://dx.doi.org/10.1136/jmedgenet-2018-105488DOI Listing
December 2018

Inotuzumab ozogamicin in pediatric patients with relapsed/refractory acute lymphoblastic leukemia.

Leukemia 2019 04 28;33(4):884-892. Epub 2018 Sep 28.

Childrens Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA.

Although inotuzumab ozogamicin (InO) is recognized as an effective agent in relapsed acute lymphoblastic leukemia (ALL) in adults, data on safety and efficacy in pediatric patients are scarce. We report the use of InO in 51 children with relapsed/refractory ALL treated in the compassionate use program. In this heavily pretreated cohort, complete remission was achieved in 67% of patients with overt marrow disease. The majority (71%) of responders were negative for minimal residual disease. Responses were observed irrespective of cytogenetic subtype or number or type of prior treatment regimens. InO was well-tolerated; grade 3 hepatic transaminitis or hyperbilirubinemia were noted in 6 (12%) and grade 3/4 infections in 11 (22%) patients. No patient developed sinusoidal obstruction syndrome (SOS) during InO therapy; however, 11 of 21 (52%) patients who underwent hematopoietic stem cell transplantation (HSCT) following InO developed SOS. Downregulation of surface CD22 was detected as a possible escape mechanism in three patients who developed a subsequent relapse after InO. We conclude that InO is a well-tolerated, effective therapy for children with relapsed ALL and prospective studies are warranted. Identification of risk factors for developing post-HSCT SOS and strategies to mitigate this risk are ongoing.
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http://dx.doi.org/10.1038/s41375-018-0265-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438769PMC
April 2019

Salivary cortisol reveals overt and hidden anxiety in survivors of childhood cancer attending clinic.

J Affect Disord 2018 11 18;240:105-112. Epub 2018 Jul 18.

Cancer Centre for Children, The Children's Hospital at Westmead, Locked Bag 4001, Sydney, NSW 2145, Australia; Children's Hospital Education Research Institute, The Children's Hospital at Westmead, Locked Bag 4001, Sydney, NSW 2145, Australia. Electronic address:

Background: Symptoms of anxiety may arise from fear of cancer recurrence and memories of traumatic experiences during treatment. This study aimed to identify changes in mental health and cortisol, a biological marker of stress, associated with oncology surveillance clinic attendance.

Methods: Adolescent and young adult (AYA) survivors of childhood cancer (aged 12-30 years, N = 46) attending a survivorship clinic were recruited. The State-Trait Anxiety Inventory, an anxiety self-rating and open answer question, and salivary cortisol collections were completed two weeks before and one day before clinic, on clinic day and two weeks after.

Results: Trait anxiety scores were consistent with the normal population. State anxiety scores two weeks after clinic were significantly lower than baseline (p = 0.02). Cortisol diurnal slopes were flatter than baseline after clinic (p = 0.02). Evening cortisol levels were significantly higher than baseline two weeks post clinic (p = 0.02).

Limitations: Combined results from biological and psychometric assessments can be difficult to interpret. Larger cohorts will further delineate cortisol pathway activity and distress in AYA cancer survivors.

Conclusions: Psychometric evidence indicates that AYA survivors of childhood cancer perceive themselves to be less anxious after a survivorship clinic visit. Biological evidence, however, indicates a dysregulation of the hypothalamic-pituitary-adrenal axis which may be linked to clinic attendance. Weak correlations suggest that cortisol may not be a reliable indicator of self-perceived anxiety. This may be due to confounding lifestyle factors influencing the stress response or potential 'coping strategies' developed during past treatment experience which may, hypothetically, have masked self-perceived anxiety.
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http://dx.doi.org/10.1016/j.jad.2018.07.035DOI Listing
November 2018

Cancer Incidence Among Children in New Caledonia, 1994 to 2012.

J Pediatr Hematol Oncol 2018 10;40(7):515-521

Oncology Unit, Children's Hospital at Westmead, Sydney, Australia.

New Caledonia (NC) is a small French territory in the Pacific Ocean with a relatively young (32% under 20) and multiethnic population. It is divided into 3 districts: Loyalty Island, the North, and the South, each with specific population characteristics. The aim of this study was to describe childhood cancer age-standardized incidence rate (ASR) in NC, compare it with the estimated one in France , and to determine whether residence and ethnicity may have an influence on intrapopulation ASR. All incident cancer cases diagnosed between 1994 and 2012 in children (0 to 14 y) resident in NC for more than 6 months were included. With 162 registered cases, the ASR for all cancers combined was 142.2 (range, 104.9 to 193.3) cases per million children per year and was not different from what was estimated in France (156.6). However, incidence varies according to the place of residence, with a higher ASR in the Loyalty Island district for several types of neoplasms, but not according to the ethnicity. The small migratory flux between this district and the rest of the territory may have led to these results, but, because of the small number of cases, no conclusion can be drawn.
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http://dx.doi.org/10.1097/MPH.0000000000001255DOI Listing
October 2018

Outcome of children with multiply relapsed B-cell acute lymphoblastic leukemia: a therapeutic advances in childhood leukemia & lymphoma study.

Leukemia 2018 11 15;32(11):2316-2325. Epub 2018 Mar 15.

The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.

The survival of pediatric patients with multiply relapsed and/or refractory (R/R) B-cell acute lymphoblastic leukemia has historically been very poor; however, data are limited in the current era. We conducted a retrospective study to determine the outcome of multiply R/R childhood B-ALL treated at 24 TACL institutions between 2005 and 2013. Patient information, treatment, and response were collected. Prognostic factors influencing the complete remission (CR) rate and event-free survival (EFS) were analyzed. The analytic set included 578 salvage treatment attempts among 325 patients. CR rates (mean ± SE) were 51 ± 4% for patients with bone marrow R/R B-ALL who underwent a second salvage attempt, 37 ± 6% for a third attempt, and 31 ± 6% for the fourth through eighth attempts combined. For patients achieving a CR after their second, third, and fourth through eighth attempts, the 2 year EFS was 41 ± 6%, 13 ± 7%, and 27 ± 13% respectively. Our results showed slight improvement when compared to previous studies. This is the largest and most recent study to date that evaluates the outcome of this patient population. Our data will provide detailed reference for the evaluation of new agents being developed for childhood B-ALL.
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http://dx.doi.org/10.1038/s41375-018-0094-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6224404PMC
November 2018

International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia.

Blood 2018 07 2;132(3):264-276. Epub 2018 May 2.

Department of Pediatric Hematology/Oncology, Charles University, Second Faculty of Medicine, Hospital Motol, Prague, Czech Republic.

Despite attempts to improve the definitions of ambiguous lineage leukemia (ALAL) during the last 2 decades, general therapy recommendations are missing. Herein, we report a large cohort of children with ALAL and propose a treatment strategy. A retrospective multinational study (International Berlin-Frankfurt-Münster Study of Leukemias of Ambiguous Lineage [iBFM-AMBI2012]) of 233 cases of pediatric ALAL patients is presented. Survival statistics were used to compare the prognosis of subsets and types of treatment. Five-year event-free survival (EFS) of patients with acute lymphoblastic leukemia (ALL)-type primary therapy (80% ± 4%) was superior to that of children who received acute myeloid leukemia (AML)-type or combined-type treatment (36% ± 7.2% and 50% ± 12%, respectively). When ALL- or AML-specific gene fusions were excluded, 5-year EFS of CD19 leukemia was 83% ± 5.3% on ALL-type primary treatment compared with 0% ± 0% and 28% ± 14% on AML-type and combined-type primary treatment, respectively. Superiority of ALL-type treatment was documented in single-population mixed phenotype ALAL (using World Health Organization and/or European Group for Immunophenotyping of Leukemia definitions) and bilineal ALAL. Treatment with ALL-type protocols is recommended for the majority of pediatric patients with ALAL, including cases with CD19 ALAL. AML-type treatment is preferred in a minority of ALAL cases with CD19 and no other lymphoid features. No overall benefit of transplantation was documented, and it could be introduced in some patients with a poor response to treatment. As no clear indicator was found for a change in treatment type, this is to be considered only in cases with ≥5% blasts after remission induction. The results provide a basis for a prospective trial.
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http://dx.doi.org/10.1182/blood-2017-12-821363DOI Listing
July 2018

A risk score including microdeletions improves relapse prediction for standard and medium risk precursor B-cell acute lymphoblastic leukaemia in children.

Br J Haematol 2018 02 30;180(4):550-562. Epub 2017 Nov 30.

Children's Cancer Institute, Lowy Cancer Research Centre, UNSW, Sydney, Australia.

To prevent relapse, high risk paediatric acute lymphoblastic leukaemia (ALL) is treated very intensively. However, most patients who eventually relapse have standard or medium risk ALL with low minimal residual disease (MRD) levels. We analysed recurrent microdeletions and other clinical prognostic factors in a cohort of 475 uniformly treated non-high risk precursor B-cell ALL patients with the aim of better predicting relapse and refining risk stratification. Lower relapse-free survival at 7 years (RFS) was associated with IKZF1 intragenic deletions (P < 0·0001); P2RY8-CRLF2 gene fusion (P < 0·0004); Day 33 MRD>5 × 10 (P < 0·0001) and High National Cancer Institute (NCI) risk (P < 0·0001). We created a predictive model based on a risk score (RS) for deletions, MRD and NCI risk, extending from an RS of 0 (RS0) for patients with no unfavourable factors to RS2 +  for patients with 2 or 3 high risk factors. RS0, RS1, and RS2 +  groups had RFS of 93%, 78% and 49%, respectively, and overall survival (OS) of 99%, 91% and 71%. The RS provided greater discrimination than MRD-based risk stratification into standard (89% RFS, 96% OS) and medium risk groups (79% RFS, 91% OS). We conclude that this RS may enable better early therapeutic stratification and thus improve cure rates for childhood ALL.
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http://dx.doi.org/10.1111/bjh.15056DOI Listing
February 2018

Predictors of thrombohemorrhagic early death in children and adolescents with t(15;17)-positive acute promyelocytic leukemia treated with ATRA and chemotherapy.

Ann Hematol 2017 Sep 8;96(9):1449-1456. Epub 2017 Jun 8.

Department of Hematology, Hospital Universitari i Politecnic La Fe, Department of Medicine, University of Valencia, Valencia, Spain.

Clinical trials on childhood acute promyelocytic leukemia (APL) report early death (ED) rates of 3-8%, but predictors of thrombohemorrhagic (TH)-ED are not well understood. In a retrospective study, we aimed to determine the incidence and predictors of TH-ED in childhood APL. Data were analyzed from children and adolescents with t(15;17)-positive APL (n = 683) who started treatment with all-trans retinoic acid (ATRA) and chemotherapy in different international studies. Demographic data; initial white blood cell (WBC), peripheral blood (PB) blast, and platelet counts; hemoglobin value; coagulation parameters; morphologic variant (M3 or M3v); and induction details were analyzed. Early death was defined as death occurring within 30 days of presentation. The incidence of ED was 4.7% (32 of 683 patients). Predictors of TH-ED were identified by univariable and multivariable Cox proportional hazard regression analyses (n = 25). In univariable analysis, high WBC (>10 × 10/L) (P < 0.001) and high PB blast (>30 × 10/L) (P < 0.001), M3v (P < 0.01), and black ethnicity (P < 0.001) were independent predictors of TH-ED. In multivariable analysis, high WBC count (P < 0.01) and obesity (i.e., body mass index ≥95th percentile for age) (P = 0.03) were predictors of TH-ED. Initial high WBC counts and obesity are likely predictors of TH-ED in childhood APL. The efficacy of novel drugs for APL-associated coagulopathy or of frontline arsenic trioxide and ATRA combination regimens in reducing ED rates in childhood APL remains to be established.
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http://dx.doi.org/10.1007/s00277-017-3042-6DOI Listing
September 2017

Tumor suppressors BTG1 and IKZF1 cooperate during mouse leukemia development and increase relapse risk in B-cell precursor acute lymphoblastic leukemia patients.

Haematologica 2017 03 15;102(3):541-551. Epub 2016 Dec 15.

Laboratory of Pediatric Oncology, Radboud university medical center, Nijmegen, the Netherlands.

Deletions and mutations affecting lymphoid transcription factor IKZF1 (IKAROS) are associated with an increased relapse risk and poor outcome in B-cell precursor acute lymphoblastic leukemia. However, additional genetic events may either enhance or negate the effects of deletions on prognosis. In a large discovery cohort of 533 childhood B-cell precursor acute lymphoblastic leukemia patients, we observed that single-copy losses of were significantly enriched in -deleted B-cell precursor acute lymphoblastic leukemia (=0.007). While deletions alone had no impact on prognosis, the combined presence of and deletions was associated with a significantly lower 5-year event-free survival (=0.0003) and a higher 5-year cumulative incidence of relapse (=0.005), when compared with -deleted cases without aberrations. In contrast, other copy number losses commonly observed in B-cell precursor acute lymphoblastic leukemia, such as or , did not affect the outcome of -deleted acute lymphoblastic leukemia patients. To establish whether the combined loss of IKZF1 and BTG1 function cooperate in leukemogenesis, -deficient mice were crossed onto an heterozygous background. We observed that loss of increased the tumor incidence of mice in a dose-dependent manner. Moreover, murine B cells deficient for and displayed increased resistance to glucocorticoids, but not to other chemotherapeutic drugs. Together, our results identify as a tumor suppressor in leukemia that, when deleted, strongly enhances the risk of relapse in -deleted B-cell precursor acute lymphoblastic leukemia, and augments the glucocorticoid resistance phenotype mediated by the loss of IKZF1 function.
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http://dx.doi.org/10.3324/haematol.2016.153023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5394950PMC
March 2017

Pineal cysts-A benign association with familial retinoblastoma.

Pediatr Hematol Oncol 2016 Sep 30;33(6):408-414. Epub 2016 Sep 30.

a Department of Oncology , Children's Hospital at Westmead , Sydney , New South Wales , Australia.

Patients with familial/heritable retinoblastoma (RB) are at increased risk of developing second malignancies throughout life, including a pineoblastoma (trilateral RB [TRB]) in early childhood. Current guidelines recommend regular surveillance brain imaging for those with heritable RB until 5 years of age. The presence of pineal cysts has been reported in patients with RB. Pineal cysts are thought to arise due to focal degeneration of the pineal gland and can be found incidentally. The finding of pineal abnormalities including cysts in children with RB on imaging is disconcerting, as it raises the possibility of an underlying malignancy, specifically a pinealoblastoma. The authors reviewed the imaging findings and clinical significance of pineal cysts in 69 patients diagnosed with RB at our center between December 1999 and November 2015. Twenty-six patients had pineal cysts found on brain magnetic resonance imaging (MRI) scans performed either at diagnosis or follow-up. Thirty-eight of 69 patients had underlying heritable RB. Nineteen of 38 familial RB patients had a pineal cyst compared with 3 out of 26 with sporadic RB (P = .004). In the majority, the imaging characteristics and size of the cysts remained stable or resolved. In this cohort, pineal cysts were detected at significantly increased frequency in heritable RB. This may be a benign association or may reflect abnormal underlying biology of pineal tissue in individuals highly susceptible to malignancy. Imaging characteristics can be helpful in distinguishing between benign and malignant lesions. The presence of a pineal cyst in patients with unilateral disease may be a useful indicator of underlying heritable RB.
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http://dx.doi.org/10.1080/08880018.2016.1225326DOI Listing
September 2016