Complete response of mantle cell lymphoma with central nervous system involvement at diagnosis with acalabrutinib - Case report.

Central nervous system (CNS) involvement by mantle cell lymphoma (MCL) is rare and portends a poor prognosis. We describe the first patient to have a complete response with front-line treatment with single-agent acalabrutinib for MCL CNS.

How I manage mantle cell lymphoma: indolent versus aggressive disease.

Mantle cell lymphoma (MCL) is a mature B-cell lymphoma with a variable clinical course and historically poor prognosis. Management is challenging in part due to the heterogeneity of the disease course, with indolent and aggressive subtypes now well recognised. Indolent MCL is often characterised by a leukaemic presentation, SOX11 negativity and low proliferation index (Ki-67). Aggressive MCL is characterised by rapid onset widespread lymphadenopathy, extra-nodal involvement, blastoid or pleomorphic histology and high Ki-67. Tumour protein p53 (TP53) aberrations in aggressive MCL are recognised with clear negative impact on survival. Until recently, trials have not addressed these specific subtypes separately. With the increasing availability of targeted novel agents and cellular therapies, the treatment landscape is constantly evolving. In this review, we describe the clinical presentation, biological factors, and specific management considerations of both indolent and aggressive MCL and discuss current and potential future evidence which may help move to a more personalised approach.

Older patients with Hodgkin Lymphoma: Walking the tightrope of efficacy and toxicity.

Since its initial description, classical Hodgkin lymphoma (cHL) portends a greatly improved prognosis and the goal of treatment in most patients is cure with minimisation of toxicity from treatment. Outcomes in older patients (>60 years old) lag behind those of their younger counterparts however, and cure remains achievable mostly for those who can tolerate full doses of conventional chemotherapy. This review addresses the difference in biology between younger and older patients with cHL and examines the impact of frailty and comorbidities on outcomes. The toxicities of conventional chemotherapy in anthracycline-fit and -unfit patients are examined, with a particular focus on pulmonary toxicity associated with bleomycin in older patients. New advances are discussed, including the possibility of using more targeted therapies such as the anti-CD30 antibody brentuximab vedotin (BV) and checkpoint inhibitors as a method of reducing dependency on conventional chemotherapy for those less well able to tolerate it. Treatment of older patients with cHL remains an area of unmet need in hematological research, and efforts to rectify this knowledge gap should continue.

Validation of Risk-Adapted Venous Thromboembolism Prediction in Multiple Myeloma Patients.

Multiple myeloma (MM) is associated with an increased risk of venous thrombosis (VTE). In the United Kingdom Medical Research Council (MRC) XI study of patients treated with immunomodulatory therapy, the VTE rate was 11.8% despite 87.7% of the patients being on thromboprophylaxis at the time of thrombosis. In order to effectively prevent VTE events in MM patients, a better understanding of patient and disease risk factors that might predict thrombosis is required. We performed a retrospective cohort analysis of over 300 newly diagnosed MM patients at a tertiary referral centre to determine the VTE rate, predictive factors for VTE, value of the Khorana score for MM VTE events and long-term mortality outcomes. Fifty-four percent of the patients were receiving thromboprophylaxis at the time of the VTE event. The mortality odds ratio was 3.3 (95% CI, 2.4-4.5) in patients who developed VTE in comparison to age-matched controls with MM. A younger age at diagnosis and higher white cell count (WCC) were found to be predictive of VTE events. Our data suggest that standard thromboprophylaxis may not be effective in preventing VTE events in myeloma patients, and alternative strategies, which could include higher-intensity thromboprophylaxis in young patients with a high WCC, are necessary.

Prefibrotic Myelofibrosis Presenting with Multiple Cerebral Embolic Infarcts and the Rare MPL W515S Mutation.

Acquired, activating mutations of MPL W515 are recognised driver mutations of the myeloproliferative neoplasms (MPN), namely, essential thrombocythemia and primary myelofibrosis. The most common mutation at this codon is W515L with several other mutations also described at a lower frequency. Of these less common mutations, MPL W515S has only been reported sporadically with limited information on clinicopathological associations. We describe the case of an elderly man with persistent thrombocytosis presenting with an ischemic cerebral event. Bone marrow biopsy showed evidence of prefibrotic myelofibrosis with targeted sequencing demonstrating the presence of the rare MPL W515S mutation. Thrombolytic and cytoreductive therapies resulted in a favorable outcome and follow-up. This case provides additional, necessary, and phenotypic data for the rare MPN-associated MPL W515S mutation.

From a direct oral anticoagulant to warfarin: reasons why patients switch.

The introduction of the direct oral anticoagulants (DOACs) has led to their widespread use for stroke prevention and venous thromboembolism, but little is known about the numbers of patients switching from a DOAC to (or back to) a warfarin or the reasons for doing so. This study was an analysis of prospectively collected data from a 4-year period surveying a warfarin dose adjustment clinic in a large city centre hospital with the primary objective to identify these reasons. In our clinic with 1791 patients annually under review, 40 patients were identified as having switched from a DOAC to warfarin with the most common reasons for switching being bleeding, re-thrombosis and renal deterioration. Other reasons included medication interactions, side effects, antiphospholipid syndrome, valvular replacement or arterial embolism. Clinical events following warfarin commencement were also recorded. Overall, these data suggest that switching from a DOAC to warfarin is seldom deemed necessary by clinicians. However, as the number of patients receiving DOACs continues to increase, it is vital that health care professionals remain vigilant regarding medication interactions, bleeding risk and changing renal function.

Screening for Malignancy in Patients With Unprovoked Venous Thromboembolism: A Single-Center Retrospective Case Series.

In this prospective review of cancer screening in unselected patients with unprovoked venous thromboembolism (VTE) presenting to a large teaching hospital in the Republic of Ireland, we aimed to determine the effects of the implementation of the National Institute for Health and Care Excellence screening policy in a "real-world" population. Within our institution, 64 individuals presented with unprovoked VTE during the study period, of whom 47 underwent a screening computed tomography (CT) scan. Two cases of previously undiagnosed cancer were identified. However, in both cases, the clinical history provided by the affected individuals would have prompted a CT scan regardless of the recommendations of the screening policy. The screening CT scans identified 18 incidental lesions within the cohort, which required further diagnostic studies. None of the additional investigations completed to date have detected any lesion of clinical significance. These findings support the view that cancer screening with CT imaging in unselected individuals with unprovoked VTE is not justified or cost-effective.