ORCID Profile
0000-0003-2306-4974
Current Organisations
University of Southampton
,
INAF
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Publisher: American Society of Clinical Oncology (ASCO)
Date: 26-10-2023
DOI: 10.1200/JCO.23.01177
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-04-2023
DOI: 10.1200/JCO.22.02473
Abstract: The International Prognostic Score (IPS) has been used in classic Hodgkin lymphoma (cHL) for 25 years. However, analyses have documented suboptimal performance of the IPS among contemporarily treated patients. Harnessing multisource in idual patient data from the Hodgkin Lymphoma International Study for In idual Care consortium, we developed and validated a modern clinical prediction model. Model development via Transparent Reporting of a multivariable prediction model for In idual Prognosis Or Diagnosis guidelines was performed on 4,022 patients with newly diagnosed advanced-stage adult cHL from eight international phase III clinical trials, conducted from 1996 to 2014. External validation was performed on 1,431 contemporaneously treated patients from four real-world cHL registries. To consider association over a full range of continuous variables, we evaluated piecewise linear splines for potential nonlinear relationships. Five-year progression-free survival (PFS) and overall survival (OS) were estimated using Cox proportional hazard models. The median age in the development cohort was 33 (18-65) years nodular sclerosis was the most common histology. Kaplan-Meier estimators were 0.77 for 5-year PFS and 0.92 for 5-year OS. Significant predictor variables included age, sex, stage, bulk, absolute lymphocyte count, hemoglobin, and albumin, with slight variation for PFS versus OS. Moreover, age and absolute lymphocyte count yielded nonlinear relationships with outcomes. Optimism-corrected c-statistics in the development model for 5-year PFS and OS were 0.590 and 0.720, respectively. There was good discrimination and calibration in external validation and consistent performance in internal-external validation. Compared with the IPS, there was superior discrimination for OS and enhanced calibration for PFS and OS. We rigorously developed and externally validated a clinical prediction model in 5,000 patients with advanced-stage cHL. Furthermore, we identified several novel nonlinear relationships and improved the prediction of patient outcomes. An online calculator was created for in idualized point-of-care use.
Publisher: Elsevier BV
Date: 05-2013
Publisher: Massachusetts Medical Society
Date: 23-06-2016
Publisher: Elsevier BV
Date: 10-2021
Publisher: Elsevier BV
Date: 07-2017
Publisher: The American Association of Immunologists
Date: 15-07-2022
Abstract: NK cells are promising cellular therapeutics against hematological and solid malignancies. Immunogenetic studies have identified that various activating killer cell Ig-like receptors (KIRs) are associated with cancer outcomes. Specifically, KIR2DS2 has been associated with reduced incidence of relapse following transplant in hematological malignancies and improved outcomes in solid tumors, but the mechanism remains obscure. Therefore, we investigated how KIR2DS2 expression impacts NK cell function. Using a novel flow cytometry panel, we show that human NK cells with high KIR2DS2 expression have enhanced spontaneous activation against malignant B cell lines, liver cancer cell lines, and primary chronic lymphocytic leukemia cells. Surface expression of CD16 was increased on KIR2DS2high NK cells, and, accordingly, KIR2DS2high NK cells had increased activation against lymphoma cells coated with the clinically relevant anti-CD20 Abs rituximab and obinutuzumab. Bulk RNA sequencing revealed that KIR2DS2high NK cells have upregulation of NK-mediated cytotoxicity, translation, and FCGR gene pathways. We developed a novel single-cell RNA-sequencing technique to identify KIR2DS2+ NK cells, and this confirmed that KIR2DS2 is associated with enhanced NK cell–mediated cytotoxicity. This study provides evidence that KIR2DS2 marks a population of NK cells primed for anticancer activity and indicates that KIR2DS2 is an attractive target for NK-based therapeutic strategies.
Publisher: Elsevier BV
Date: 05-2018
Publisher: American Society of Hematology
Date: 24-03-2016
DOI: 10.1182/BLOOD-2015-11-679407
Abstract: PET-CT is the modern standard for staging Hodgkin lymphoma and can replace contrast enhanced CT in the vast majority of cases. Agreement between expert and local readers is sufficient for the Deauville criteria to assess response in clinical trials and the community.
Location: United Kingdom of Great Britain and Northern Ireland
Location: No location found
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Peter Johnson.