A Case of Hemophagocytic Lymphohistiocytosis Triggered by Disseminated Tuberculosis and Hairy Cell Leukaemia after SARS-CoV2 Infection

Hemophagocytic Lymphohistiocytosis (HLH) is a rare but life-threatening disease that can occur either as a primary condition or as a consequence of a variety of triggers, including infectious diseases. Here we present a case of secondary HLH triggered by systemic Mycobacterium tuberculosis infection in a 59-year-old immunocompromised Hairy Cell Leukemia and previous SARS-CoV2 infected patient. This case report underlines the role of Etoposide-based chemotherapy in treating the severe inflammation that is the defining factor of HLH, suggesting how, even when such therapy is not effective, it may still give the clinicians time to identify the underlying condition and start the appropriate targeted therapy. Moreover, it gives insight on our decision to treat the underlying haematological condition with a BRAF-targeted therapy rather than purine analog-based chemotherapy to reduce the risk of future severe infections.

Very high prevalence of infection with the human T cell leukaemia virus type 1c in remote Australian Aboriginal communities: Results of a large cross-sectional community survey

Infection with the human T cell leukaemia virus type 1 (HTLV-1) subtype C is endemic among Aboriginal people in central Australia. To provide insights into the risk factors for transmission, we conducted the first large-scale, community-based prevalence study in seven remote Aboriginal communities. Residents >2 years old were invited to participate in the study between August 2014 and June 2018. HTLV-1 infection was defined as a positive western blot (WB) test or a positive HTLV-1 PCR. 720 community residents participated in the study (children <15 years, 142; adults, 578). Prevalences for children and adults were 3.5% (5/142) and 36.8% (213/578), respectively, reaching 49.3% (106/215) for those older than 45 years. A wide range of proviral loads were measured for both asymptomatic and symptomatic participants with no difference within groups according to age or gender; however, median PVL was 1.34 log10 higher for symptomatic participants. The adult prevalence of HTLV-1 infection in central Australia is the highest reported worldwide. Sexual contact is likely to be the predominant mode of transmission.

Successful treatment of smouldering Human T cell Leukemia Virus Type1 associated bronchiolitis and alveolar abnormalities with amplified natural killer therapy

In amplified natural killer (ANK) cell immunotherapy, NK cells are extracted from the patient’s blood, cultured for enhancing its anticancer effects and amplified before they are returned to the body. Here, we administered ANK therapy to an 81-year-old female patient diagnosed with smouldering human T cell leukaemia virus-associated bronchioloalveolar disorder. After eight sessions of twice-weekly NK cell infusion, the bilateral diffuse granular shadows on a CT scan and the overall respiratory function improved markedly. Later, the patient received outpatient treatment without serious side effects. Thus, ANK therapy may be safe for elderly patients owing to its infrequent side effects.

Anti-CD19 monoclonal antibodies for the treatment of relapsed or refractory B-cell malignancies: a narrative review with focus on diffuse large B-cell lymphoma

Purpose CD19 is a cell surface protein that is found on both healthy and malignant B cells. Accordingly, it has become an important target for novel treatments for non-Hodgkin lymphomas and B-cell leukaemia. Three anti-CD19 monoclonal antibodies with distinct mechanisms of action have been developed for the treatment of B-cell malignancies. Methods We reviewed the preclinical and clinical data on the development of the newly approved anti-CD19 monoclonal antibodies blinatumomab, tafasitamab and loncastuximab tesirine, and consider their place in the treatment of relapsed or refractory B-cell malignancies. Results Blinatumomab is a bispecific T-cell engager that binds to both CD19 on B cells and CD3 on T cells, facilitating antibody-dependent cytotoxicity. Blinatumomab significantly prolongs overall survival in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia, although cytokine release syndrome and severe neurotoxicity may necessitate discontinuation. Tafasitamab, which has modified anti-CD19 Fab and Fc regions, has significantly enhanced affinity for both CD19 and effector cell receptors compared with unmodified anti-CD19. In L-MIND, tafasitamab plus lenalidomide provided an overall response rate (ORR) of 57.5% in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in patients non-transplant eligible. Loncastuximab tesirine is an antibody–drug conjugate that has been studied as monotherapy and in combination with ibrutinib in 3L + relapsed or refractory DLBCL. The ORR was 48.3% in a phase II trial of loncastuximab tesirine. The optimal place of anti-CD19 monoclonal antibodies in therapy has yet to be determined, but the prospect of improved outcomes for at least some patients with treatment-resistant B-cell malignancies appears likely, particularly in those with limited therapeutic options and poor prognosis.

Myelopathy associated with intrathecal methotrexate

A 21-year-old man developed progressive and bilateral lower limb numbness, gait impairment and urinary incontinence over 10 days. He had received intrathecal methotrexate 20 days previously for acute lymphoblastic B-cell leukaemia, following 7 months of systemic chemotherapy. MR scan of the spinal cord showed bilateral symmetric and extensive T2/fluid attenuated inversion recovery (FLAIR) increased signal involving the dorsal columns in the thoracic cord. His serum folate concentration was at the lower end of the normal range. We stopped the intrathecal chemotherapy and gave folate; after a few days, he progressively improved. Myelopathy is an important adverse effect of intrathecal methotrexate, which may cause clinical and imaging features resembling subacute combined degeneration of the spinal cord. CNS infiltration must be excluded, intrathecal chemotherapy stopped and deficiency of folate or vitamin B12 treated as appropriate.

Bovine Leukaemia Virus: Current Epidemiological Circumstance and Future Prospective

Bovine leukaemia virus (BLV) is a deltaretrovirus that is closely related to human T-cell leukaemia virus types 1 and 2 (HTLV-1 and -2). It causes enzootic bovine leukosis (EBL), which is the most important neoplastic disease in cattle. Most BLV-infected cattle are asymptomatic, which potentiates extremely high shedding rates of the virus in many cattle populations. Approximately 30% of them show persistent lymphocytosis that has various clinical outcomes; only a small proportion of animals (less than 5%) exhibit signs of EBL. BLV causes major economic losses in the cattle industry, especially in dairy farms. Direct costs are due to a decrease in animal productivity and in cow longevity; indirect costs are caused by restrictions that are placed on the import of animals and animal products from infected areas. Most European regions have implemented an efficient eradication programme, yet BLV prevalence remains high worldwide. Control of the disease is not feasible because there is no effective vaccine against it. Therefore, detection and early diagnosis of the disease are essential in order to diminish its spreading and the economic losses it causes. This review comprises an overview of bovine leukosis, which highlights the epidemiology of the disease, diagnostic tests that are used and effective control strategies.

SP1.1.7PBX4 functions as a novel oncogene and promotes angiogenesis in colorectal cancer: A comprehensive analysis of the PBX gene family

Aims Pre-B-cell Leukaemia (PBX) genes are important in organ development during embryogenesis. To date, four members of the PBX family (PBX1, PBX2, PBX3, PBX4) have been identified to be involved in human cancers, but little is known about their role in colorectal cancer (CRC). The aim of this study was to determine their differential expression, prognostic role and function in CRC. Methods Molecular and overall survival (OS) data from 614 patients with CRC were obtained from the National Cancer Institute, Tissue Cancer Genome Atlas (TCGA) database. To investigate the differential PBX gene mRNA expression, we performed a comparative cancer to normal computational analysis in edgeR. To determine PBXs prognostic value, we conducted Kaplan-Meier survival analysis and COX regression, selecting 10-year OS as primary outcome. Lastly, to explore the effect of PBX4 in CRC cell growth and angiogenesis, we performed gene expression modulation experiments using a PBX4-overexpressing plasmid-vector. Cell proliferation and VEGFA angiogenic factor expression were defined as primary and secondary in vitro outcomes respectively. Results Among PBXs only PBX4 was significantly upregulated showing a 4-fold increase in CRC vs normal colon (p &lt; 0.0001). Survival analysis showed that only high PBX4 mRNA expression was associated with increased risk for worse OS in patients with CRC (HR:1.3 95%CI:1-1.6, p = 0.02). Functionally, overexpression of PBX4 significantly increased CRC cell proliferation in vitro (p &lt; 0.001) and markedly upregulated the expression of VEGFA (p &lt; 0.0001). Conclusions Comprehensive analysis of the PBX gene family identifies that PBX4 may function as a novel oncogene and may promote angiogenesis through VEGFA in CRC.