A5001836891- Acute Lymphoblastic Leukemia research
- Childhood Cancer Survivors' Quality of Life
- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- Hematopoietic Stem Cell Transplantation
- CAR-T cell therapy research
- Cancer Genomics and Diagnostics
- Glioma Diagnosis and Treatment
- Neuroblastoma Research and Treatments
- Lymphoma Diagnosis and Treatment
- Neonatal Health and Biochemistry
- Cancer survivorship and care
- Congenital Diaphragmatic Hernia Studies
- Neutropenia and Cancer Infections
- Single-cell and spatial transcriptomics
- Brain Metastases and Treatment
- Immune Cell Function and Interaction
- Palliative Care and End-of-Life Issues
- Multiple and Secondary Primary Cancers
- Renal Transplantation Outcomes and Treatments
- RNA modifications and cancer
- Folate and B Vitamins Research
- NF-κB Signaling Pathways
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
Bristol Royal Hospital for Children
2016-2025
University Hospitals Bristol NHS Foundation Trust
2012-2024
Royal Hospital for Sick Children
1999-2024
Newcastle University
2017-2021
University College London
2017-2021
Great Ormond Street Hospital
2017-2021
Blood Cancer UK
2021
University of Bristol
2004-2020
Royal Hospital for Children
2017-2020
Jazz Pharmaceuticals (Italy)
2017
Amplicon-based next-generation sequencing (NGS) of immunoglobulin (IG) and T-cell receptor (TR) gene rearrangements for clonality assessment, marker identification quantification minimal residual disease (MRD) in lymphoid neoplasms has been the focus intense research, development application. However, standardization validation a scientifically controlled multicentre setting is still lacking. Therefore, IG/TR assay design, including bioinformatics, was performed within EuroClonality-NGS...
Purpose Minimal residual disease (MRD) and genetic abnormalities are important risk factors for outcome in acute lymphoblastic leukemia. Current algorithms dichotomize MRD data do not assimilate genetics when assigning risk, which reduces predictive accuracy. The aim of our study was to exploit the full power by examining it as a continuous variable integrate with genetics. Patients Methods We used population-based cohort 3,113 patients who were treated UKALL2003, median follow-up 7 years....
Assessment of clonality, marker identification and measurement minimal residual disease (MRD) immunoglobulin (IG) T cell receptor (TR) gene rearrangements in lymphoid neoplasms using next-generation sequencing (NGS) is currently under intensive development for use clinical diagnostics. So far, however, there a lack suitable quality control (QC) options with regard to standardisation metrics ensure robust application such approaches. The EuroClonality-NGS Working Group has therefore...
Abstract Patients with relapsed/refractory acute lymphoblastic leukemia (ALL) or lymphoma (LL) have poor outcomes compared newly diagnosed, treatment-naïve patients. The phase 2, open-label DELPHINUS study evaluated daratumumab (16 mg/kg IV) plus backbone chemotherapy in children B-cell ALL (n = 7) after ≥2 relapses, and young adults T-cell (children, n 24; adults, 5) LL 10) first relapse. primary end point was complete response (CR) the (end of cycle 2) 1) cohorts, which patients could...
Purpose Our aim was to determine the role of end-of-induction (EOI) minimal residual disease (MRD) assessment in identification and stratification induction failure patients with pediatric acute lymphoblastic leukemia (ALL) identify genetic abnormalities that drive these patients. Patients Methods Analysis included 3,113 who were treated Medical Research Council UKALL2003 multicenter randomized trial (NCT00222612) between 2003 2011. MRD measured by using standardized real-time quantitative...
High hyperdiploidy is the most common genetic subtype of childhood acute lymphoblastic leukaemia and associated with a good outcome. However, some patients relapse and, given its prevalence, high account for large proportion all relapses. We aimed to evaluate putative risk factors determine optimal pattern trisomies predicting outcome.We used discovery validation cohorts from consecutive trials-UKALL97/99 (n=456) UKALL2003 (n=725)-to develop prognostic profile. UKALL97/99 recruited aged 1-18...
10001 Background: Approximately 15-20% of pediatric pts with ALL or LL will be refractory to/relapse after frontline treatment; relapsed disease is associated poor outcomes. In a phase 2 study, 7 (28.6%) T-cell in first relapse achieved complete response (CR) using the vincristine, prednisone, PEG-asparaginase, and doxorubicin (VPLD) reinduction backbone. DARA, human IgGκ monoclonal antibody targeting CD38 approved for treating multiple myeloma, has shown preclinical efficacy models. We...
PURPOSE We tested whether blinatumomab (Blina) is effective as a toxicity-sparing alternative to first-line intensive chemotherapy in children and young persons (CYP) with B-ALL who were chemotherapy-intolerant or chemotherapy-resistant. METHODS Data collected for consecutive CYP (age 1-24 years) Philadelphia chromosome–positive chromosome–negative received Blina therapy. was given replacement postremission patients intolerance resistance. responders further (Blin-CT) first remission...
Malignant melanoma (MM) is one of the least common types childhood cancer, accounting for less than 1% all pediatric malignancies. Neurocutaneous melanosis (NCM) a rare phakomatosis consisting congenital abnormal pigmentation skin and meninges. The meningeal lesions are particularly prone to malignant change.The authors describe 5 patients with NCM 1 primary leptomeningeal (LMM) seen at 2 treatment centers in north England over 13-year period (1984-1997).The clinical features, progress,...
Abstract Patients with an ABL‐class fusion have a high risk of relapse on standard chemotherapy but are sensitive to tyrosine kinase inhibitors (TKI). In UKALL2011, we screened patients post‐induction MRD ≥1% and positive (12%) received adjuvant TKI. As the intervention started during not all eligible were prospectively. Retrospective screening allowed outcome equivalent who did receive TKI in first remission be compared. had reduced relapse/refractory disease: 0% vs. 63% at four years ( P = 0·009).
PURPOSE The aim of the randomized trial, UKALL2003, was to adjust treatment intensity on basis minimal residual disease (MRD) stratification for children and young adults with acute lymphoblastic leukemia. We analyzed 10-year outcomes time patients be considered cured (ClinicalTrials.gov identifier: NCT00222612 ). METHODS A total 3,113 were including 1,054 who underwent random assignment (521 MRD low-risk 533 high-risk patients). Time cure defined as point at which chance relapse < 1%....
UKALL 2011 randomly assigned children and young adults (younger than 25 years) with ALL or lymphoblastic lymphoma. The aims were to reduce induction toxicity (randomization 1 [R1]), CNS relapse risk 2 [R2]-interim maintenance [R2IM]), morbidity (R2pulses). R1 compared dexamethasone (dex) for 28 days (6 mg/m2; standard) 14 (10 short). R2 was a factorial randomization resulting in four arms: high-dose methotrexate (HDM) pulses, HDM without standard interim (SIM) pulses (standard of care), SIM...
Receptor tyrosine-like orphan receptor (ROR)1 is overexpressed in some hematological cancers but has low expression normal tissues, making it a potential therapeutic target. We investigated this childhood B cell precursor (BCP) and T acute lymphoblastic leukemia (ALL) cases. The proportion of ROR1+ cells was significantly higher T-ALL (median 13.8%, range 2.9-87%) than BCP-ALL (6%, 0.3-83%, P=0.02). Antigen density also lower 1027, 876-2588) compared to (1089, 865-1527). In propagating...
To evaluate the safety of transfusing pooled, whole blood-derived granulocytes in additive solution and plasma (GASP) 30 recipients.Demand for England has increased five-fold. With advantages reduced red cell, overall volume, GASP maintains function vitro.Observations were recorded prior to post transfusion. Increments at 1 h following morning. Leucocyte antibody screening was undertaken 1-6 months transfusion.Thirty patients aged between 8 68 years received 221 148 transfusion episodes....
Abstract Purpose: We investigated nilotinib exposure in pediatric patients with chronic myeloid leukemia (CML) or Philadelphia chromosome–positive (Ph+) acute lymphoblastic (ALL) resistant to, relapsed on, refractory intolerant of previous treatment. Patients and Methods: Fifteen (aged 1–&lt;18 years) CML to imatinib and/or dasatinib (n = 11) Ph+ ALL on standard therapy 4) enrolled this phase I study. Nilotinib (230 mg/m2 twice daily; equivalent the adult 400-mg twice-daily dose) was...