ORCID Profile
0009-0000-1621-4327
Current Organisations
Liverpool Hospital
,
University of New South Wales
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Publisher: Informa UK Limited
Date: 04-2006
Publisher: Elsevier BV
Date: 05-2008
Publisher: Springer Science and Business Media LLC
Date: 03-03-2014
DOI: 10.1038/BMT.2014.23
Publisher: Springer Science and Business Media LLC
Date: 23-09-2014
DOI: 10.1038/BMT.2013.142
Abstract: This was an Australasian Bone Marrow Transplant Recipient Registry (ABMTRR)-based retrospective study assessing the outcome of Fludarabine Melphalan (FluMel) reduced-intensity conditioning between 1998 and 2008. Median follow-up was 3.4 years. There were 344 patients with a median age of 54 years (18-68). In all, 234 patients had myeloid malignancies, with AML (n=166) being the commonest indication. There were 110 lymphoid patients with non-hodgkins lymphoma (NHL) (n=64) the main indication. TRM at day 100 was 14% with no significant difference between the groups. OS and disease-free survival (DFS) were similar between myeloid and lymphoid patients (57 and 50% at 3 years, respectively). There was no difference in cumulative incidence of relapse or GVHD between groups. Multivariate analysis revealed four significant adverse risk factors for DFS: donor other than HLA-identical sibling donor, not in remission at transplant, previous autologous transplant and recipient CMV positive. Chronic GVHD was associated with improved DFS in multivariate analysis predominantly due to a marked reduction in relapse (HR:0.44, P=0.003). This study confirms that FluMel provides durable and equivalent remissions in both myeloid and lymphoid malignancies. Disease stage and chronic GVHD remain important determinants of outcome for FluMel allografting.
Publisher: Springer International Publishing
Date: 2021
Publisher: Springer Science and Business Media LLC
Date: 31-03-2011
Abstract: Diagnostic accuracy of lymphoma, a heterogeneous cancer, is essential for patient management. Several ancillary tests including immunophenotyping, and sometimes cytogenetics and PCR are required to aid histological diagnosis. In this proof of principle study, gene expression microarray was evaluated as a single platform test in the differential diagnosis of common lymphoma subtypes and reactive lymphadenopathy (RL) in lymph node biopsies. 116 lymph node biopsies diagnosed as RL, classical Hodgkin lymphoma (cHL), diffuse large B cell lymphoma (DLBCL) or follicular lymphoma (FL) were assayed by mRNA microarray. Three supervised classification strategies (global multi-class, local binary-class and global binary-class classifications) using diagonal linear discriminant analysis was performed on training sets of array data and the classification error rates calculated by leave one out cross-validation. The independent error rate was then evaluated by testing the identified gene classifiers on an independent (test) set of array data. The binary classifications provided prediction accuracies, between a subtype of interest and the remaining s les, of 88.5%, 82.8%, 82.8% and 80.0% for FL, cHL, DLBCL, and RL respectively. Identified gene classifiers include LIM domain only-2 ( LMO2 ), Chemokine (C-C motif) ligand 22 ( CCL22 ) and Cyclin-dependent kinase inhibitor-3 ( CDK3 ) specifically for FL, cHL and DLBCL subtypes respectively. This study highlights the ability of gene expression profiling to distinguish lymphoma from reactive conditions and classify the major subtypes of lymphoma in a diagnostic setting. A cost-effective single platform "mini-chip" assay could, in principle, be developed to aid the quick diagnosis of lymph node biopsies with the potential to incorporate other pathological entities into such an assay.
Publisher: Wiley
Date: 11-11-2008
DOI: 10.1111/J.1365-2141.2008.07401.X
Abstract: Clinicians must promptly decide which patients suspected of having heparin-induced thrombocytopenia (HIT) warrant a change in anticoagulation. This single-centre series of 246 HIT testing referrals assessed the combination of clinical score (thrombocytopenia, timing, thrombosis, other causes of thrombocytopenia not evident 4T's), Diamed ID-Heparin-PF4 immunoassay (PaGIA) and 14C Serotonin Release Assay (SRA) to develop a practical and safe diagnostic strategy for HIT. A total of 142/256 (58%) referrals were in patients with a low 4T's score, with 12/246 (5%) in the high scoring group. PaGIA was positive in 24/246 (9.7%) patients, whilst SRA was positive in 9/246 (3.6%). The overall positive predictive value of a positive PaGIA test alone was 37.5%, however this reached 80% for the high scoring group. Both negative PaGIA and low clinical score independently had negative predictive values of 100%. We subsequently developed an algorithm that, when applied to this cohort, would have resulted in 18/246 patients (7%) definitely requiring alternative anticoagulation, whilst a further 7/246 (2.8%) patients would have been considered on an in idual basis. Ultimately (based on SRA) this would have resulted in 16/246 (6.5%) patients unnecessarily having a change in their anticoagulation, with 9/246 (3.6%) patients being 'correctly treated'. The combination of 4T's scoring and PaGIA permitted a practical and safe approach to rapid HIT diagnosis and management.
Publisher: Elsevier BV
Date: 04-2009
DOI: 10.1080/00313020902756287
Abstract: MicroRNAs (miRNAs) are recently discovered short non-coding RNA molecules that negatively regulate messenger RNA (mRNA) translation to protein. Their discovery heralds a novel mechanism of post-transcriptional gene regulation and has lead to a cascade of studies aimed at identifying how miRNA dysregulation may contribute to disease. Recent studies have provided indisputable evidence for a role of miRNAs in normal haematopoiesis adding a further layer of complexity to the regulatory process. Leukaemia and lymphoma are characterised by dysregulation of survival and differentiation in haematopoietic progenitor cells. There are several lines of evidence supporting the notion that miRNA dysfunction is contributory, whether by extrapolation from miRNA-mediated oncogenesis in other disorders, by miRNA profiling, or by in vivo and in vitro functional studies of miRNAs in haematological malignancies. Further work is underway to delineate the role of miRNAs in the pathogenesis of malignant blood disorders, with the eventual hope that this will aid in the diagnosis and the development of potential novel cures for such diseases, many of which still have an unacceptable prognosis.
Publisher: Springer Science and Business Media LLC
Date: 19-10-2020
Publisher: Springer Science and Business Media LLC
Date: 05-04-2014
Publisher: Elsevier BV
Date: 06-2014
DOI: 10.1016/J.CLML.2013.10.003
Abstract: The standard-risk (SR) subgroup of acute lymphoblastic leukemia in adults (aALL) is a heterogeneous category, with a 20% to 40% relapse rate and a wide range of relapse-free survival (RFS) and overall survival (OS). There is a need to identify at the outset those patients with SR-aALL who are likely to have shorter RFS and OS, so they can be treated more aggressively. Flow cytometric data of 81 patients with SR-aALL treated with a standardized protocol were retrospectively analyzed. Thirty-two patients (40%) relapsed the median RFS and OS were 12.5 months (range, 1-136 months) and 30 months (range, 3-235 months), respectively. Twenty-six patients survived ≥ 48 months. Expression of myeloid antigen CD13, using the conventional ≥ 20% threshold and a lower ≥ 5% threshold, was seen in 17 (29%) of 59 and 29 (49%) of 59 patients, respectively, whereas dual expression of CD13 and CD33 was seen in 8 patients. CD13 positivity at ≥ 20% and ≥ 5% threshold was associated with a shorter RFS (P = .0158 and P < .0001, respectively) and OS (P = .0072 and P < .0001, respectively). Dual expression of CD13 (at ≥ 5% or ≥ 20% threshold) and CD33 was associated with inferior OS (P = .0038 and P = .0032, respectively) and RFS (P = .0705 and P = .2516, respectively). For ≥ 20% and ≥ 5% threshold of positivity, 16 of 42 and 28 of 42 who survived < 48 months were positive, compared with 1 of 17 and 1 of 17 who survived ≥ 48 months (P = .0133 and P < .0001, respectively). Aberrant expression of CD13 in ≥ 5% of blasts of patients with SR-aALL is an adverse prognostic factor, delineating a subgroup of patients with SR-aALL that should be considered for more aggressive treatment.
Publisher: SAABRON PRESS
Date: 19-01-2023
DOI: 10.1007/S44228-022-00023-5
Abstract: This phase 1 trial assessed the safety, pharmacokinetics, and preliminary antitumor activity of RO7297089, an anti-BCMA/CD16a bispecific antibody. RO7297089 was administered weekly by intravenous infusion to patients with relapsed/refractory multiple myeloma. The starting dose was 60 mg in this dose-escalation study utilizing a modified continual reassessment method with overdose control model. Overall, 27 patients were treated at doses between 60 and 1850 mg. The maximally administered dose was 1850 mg due to excipients in the formulation that did not allow for higher doses to be used. The maximum tolerated dose was not reached. The most common adverse events irrespective of grade and relationship to the drug were anemia, infusion-related reaction, and thrombocytopenia. Most common treatment-related grade ≥ 3 toxicities were ALT/AST increase and reduced lymphocyte count. Pharmacokinetic studies suggested non-linear pharmacokinetics and target-mediated drug disposition, with a trend of approaching linear pharmacokinetics at doses of 1080 mg and higher. Partial response was observed in two patients (7%), minimal response in two patients (7%), and stable disease in 14 patients (52%). RO7297089 was well tolerated at doses up to 1850 mg, and the efficacy data supported activity of RO7297089 in multiple myeloma. Combination with other agents may further enhance its potential as an innate immune cell engager in multiple myeloma. ClinicalTrials.gov: NCT04434469 Registered June 16, 2020 t2/show/NCT04434469 .
Publisher: Elsevier BV
Date: 10-2020
Publisher: Elsevier BV
Date: 04-2010
DOI: 10.1016/J.CYTO.2009.12.001
Abstract: The interleukin (IL)-7 receptor (IL-7R) is expressed on human pre-B but not mature B-cells. We hypothesised that aberrant expression of IL-7R contributes to B-cell oncogenesis. Surface expression of IL-7R components CD127 and CD132, and intracellular Ki-67 and Bcl-2 were examined by flow cytometry on peripheral blood or bone marrow mononuclear cells (PBMC BMMC) from patients with B-cell derived neoplasms, chronic human immunodeficiency virus type-1 (HIV-1) infection alone, or healthy volunteers. Plasma IL-7, IL-2, IL-4, IL-6, IL-10, IL-21, TNF-alpha, IFN-gamma and BAFF were measured by enzyme-linked immuno-sorbent assay or bead array. The effects of exogenous IL-7 on PBMC and BMMC were examined. CD127 expression was elevated in pre-B-cell acute lymphoblastic leukemia (pre-B-ALL) and in some cases of Non-Hodgkin's Lymphoma (B-NHL). Plasma IL-7 levels were higher in pre-B-ALL, B-cell chronic lymphocytic leukemia (B-CLL) and HIV-1 associated B-NHL (HIV-B-NHL) compared with control groups. CD127+ pre-B-ALL cells had higher expression of Ki-67, Bcl-2 and CD132 than CD127- counterparts. Unlike T-lineage cells, CD127+ pre-B-ALL cells did not down-regulate CD127 in response to exogenous IL-7. Patients with B-cell derived neoplasms had elevated circulating IL-10 and decreased BAFF. These findings support a role for the IL-7/IL-7R system in B-cell oncogenesis.
No related grants have been discovered for Adam Jacob Bryant.