Publications by authors named "Stephen Mulligan"

Population-based studies have demonstrated a high risk of second cancers, especially of the skin, among patients with chronic lymphocytic leukaemia (CLL). We describe age-standardised incidence ratios (SIRs) of second primary malignancies (SPM) in Australian patients with relapsed/refractory CLL treated with at least two lines of therapy, including ibrutinib. From December 2014 to November 2017, 156 patients were identified from 13 sites enrolled in the Australasian Lymphoma and Related Diseases Registry, and 111 had follow-up data on rates of SPM.

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  • The phase 3 ASPEN trial compared the effectiveness of two BTK inhibitors, zanubrutinib and ibrutinib, in treating Waldenström macroglobulinemia, analyzing genetic mutations' impact on treatment response.
  • The study found that patients with mutations in CXCR4 and TP53 had poorer responses and survival rates but those treated with zanubrutinib generally showed better outcomes than those given ibrutinib.
  • Overall, the research indicated that zanubrutinib offers improved clinical outcomes for patients with specific mutations compared to ibrutinib, highlighting the importance of genetic testing in treatment decision-making.
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Despite advances in treatment, a significant proportion of patients with chronic lymphocytic leukemia (CLL) will relapse with drug-resistant disease. The imipridones, ONC-201 and ONC-212, are effective against a range of different cancers, including acute myeloid leukemia (AML) and tumors of the brain, breast, and prostate. These drugs induce cell death through activation of the mitochondrial protease, caseinolytic protease (CIpP), and the unfolded protein response (UPR).

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Despite widespread vaccination rates, we are living with high transmission rates of SARS-CoV-2. Although overall hospitalisation rates are falling, the risk of serious infection remains high for patients who are immunocompromised because of haematological malignancies. In light of the ongoing pandemic and the development of multiple agents for treatment, representatives from the Haematology Society of Australia and New Zealand and infectious diseases specialists have collaborated on this consensus position statement regarding COVID-19 management in patients with haematological disorders.

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  • Patients with chronic lymphocytic leukemia (CLL) have a significantly heightened risk of developing other malignancies (OMs), with a study tracking nearly 20,000 CLL patients revealing 3,513 OMs diagnosed over 129,254 years of follow-up.
  • The study found that treatment with fludarabine and cyclophosphamide increased the likelihood of developing myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), while non-melanoma skin cancer (NMSC) and prostate cancer were common solid tumors in treated patients.
  • Importantly, patients with CLL who developed OMs had lower overall survival rates, especially those diagnosed with AML and MDS, highlighting that C
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  • In Australia, over 50% of patients with relapsed or refractory chronic lymphocytic leukaemia on ibrutinib also take proton pump inhibitors (PPIs).
  • High gastric pH caused by PPIs can lower the effectiveness of some Bruton tyrosine kinase inhibitors, including ibrutinib.
  • The study found no significant impact of PPI use on how long patients remain on ibrutinib treatment (P = 0.61), indicating that PPIs do not affect treatment persistence.
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  • - Chronic lymphocytic leukaemia (CLL) is the most common blood cancer in Australia and New Zealand, with significant advancements in diagnosis and treatment in the past decade.
  • - New technologies like next-generation sequencing and flow cytometry help doctors predict outcomes and monitor treatment responses more effectively, while new therapies have improved care for patients, especially those with high-risk genetic issues.
  • - Given the unique healthcare landscape in Australasia, experts have created a consensus practice statement to provide standardized guidelines for CLL diagnosis and management, keeping in mind public health concerns like the COVID-19 pandemic.
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We analysed COVID-19 infection outcomes of 129/241 chronic lymphocytic leukaemia (CLL) (53.9%) and 22/55 monoclonal B-lymphocytosis (MBL) (40.0%) patients following multiple vaccine doses aiming for maximum measured anti-spike antibody response.

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  • The phase III ASPEN study showed that zanubrutinib is as effective as ibrutinib but has better safety for treating patients with Waldenström macroglobulinemia (WM).
  • In a long-term follow-up, zanubrutinib demonstrated higher rates of very good partial response and complete response compared to ibrutinib in both cohorts of WM patients.
  • Adverse events like diarrhea, muscle spasms, and hypertension were more common with ibrutinib, while zanubrutinib had a lower risk of treatment-related discontinuation.
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Patients with chronic lymphocytic leukemia (CLL) progressing on ibrutinib constitute an unmet need. Though Bruton tyrosine kinase (BTK) and PLCG2 mutations are associated with ibrutinib resistance, their frequency and relevance to progression are not fully understood. In this multicenter retrospective observational study, we analyzed 98 patients with CLL on ibrutinib (49 relapsing after an initial response and 49 still responding after ≥1 year of continuous treatment) using a next-generation sequencing (NGS) panel (1% sensitivity) comprising 13 CLL-relevant genes including BTK and PLCG2.

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Ibrutinib is a small molecule inhibitor of Bruton's tyrosine kinase indicated for the treatment of relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL). The Named Patient Program in Australia and New Zealand (ANZ NPP) provided access to ibrutinib treatment to 1126 R/R CLL/SLL and 330 R/R MCL patients, prior to Pharmaceutical Benefits Scheme listing. This study aimed to assess the duration of treatment for the ANZ NPP patients, as an indicator of efficacy and tolerability of ibrutinib in the real world.

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Chronic lymphocytic leukaemia (CLL) is invariably accompanied by some degree of immune failure, and CLL patients have a high rate of second primary malignancy (SPM) compared to the general population. We comprehensively documented the incidence of all forms of SPM including skin cancer (SC), solid organ malignancy (SOM), second haematological malignancy (SHM) and separately Richter's syndrome (RS) across all therapy eras. Among the 517 CLL/small lymphocytic lymphoma (SLL) patients, the overall incidence of SPMs with competing risks was SC 31.

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Since first described almost two decades ago, there has been significant evolution in our definition and understanding of the biology and implications of monoclonal B-cell lymphocytosis (MBL). This review provides an overview of the definition, classification, biology, and natural history of MBL, mainly focused on the dominant CLL-like phenotype form of MBL. The increasingly recognized implications of MBL with respect to immune dysfunction are discussed, particularly in view of the COVID-19 pandemic, along with management recommendations for MBL in the clinic.

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Objectives: To analyse total national utilisation of immunoglobulin (Ig) replacement therapy (IgRT) for Chronic Lymphocytic Leukaemia patients with acquired hypogammaglobulinaemia and severe and/or recurrent bacterial infections.

Methods: In 2007, the National Blood Authority first published Criteria for the clinical use of intravenous immunoglobulin in Australia. The Australian Red Cross Lifeblood assessed, approved, and recorded all supply with patient demographics, distribution data, intravenous Ig (IVIg) volumes and treatment episodes.

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Chronic lymphocytic leukaemia (CLL) is associated with immunocompromise and high risk of severe COVID-19 disease and mortality. Monoclonal B-cell lymphocytosis (MBL) patients also have immune impairment. We evaluated humoural and cellular immune responses in 181 patients with CLL (160) and MBL (21) to correlate failed seroconversion [<50 AU/ml SARS-CoV-2 II IgG assay, antibody to spike protein; Abbott Diagnostics)] following each of two vaccine doses with clinical and laboratory parameters.

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Triple combination FCR (fludarabine, cyclophosphamide and rituximab) is often used as front-line treatment for chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma. Results from our laboratory indicate that 2-FaraAMP (fludarabine) has multiple mechanisms of cytotoxicity that include accumulation of isoforms and phosphorylated derivatives of p53, and induction of the unfolded protein response (UPR). Using protein pull-downs with Dynabeads coated with p53 antibody, we have found that 2-FaraA (fludarabine nucleoside) induces major changes in the p53 interactome in human Raji lymphoma and IM9 multiple myeloma cells.

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Assessment of measurable residual disease (often referred to as "minimal residual disease") has emerged as a highly sensitive indicator of disease burden during and at the end of treatment and has been correlated with time-to-event outcomes in chronic lymphocytic leukemia. Undetectable-measurable residual disease status at the end of treatment demonstrated independent prognostic significance in chronic lymphocytic leukemia, correlating with favorable progression-free and overall survival with chemoimmunotherapy. Given its utility in evaluating depth of response, determining measurable residual disease status is now a focus of outcomes in chronic lymphocytic leukemia clinical trials.

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