Quantification of T cell clonality in human T cell leukaemia virus type-1 carriers can detect the development of adult T cell leukaemia early

Wolf, Sonia N; Haddow, Jana; Greiller, Claire; Taylor, Graham P.; Cook, Lucy; Rowan, Aileen

doi:10.1038/s41408-021-00458-8

Cited by 13 publications

(10 citation statements)

References 26 publications

(26 reference statements)

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“…Developing disease is positively correlated with the proviral load (PVL) (≥4%), and in the case for ATLL, an oligoclonality index determined by flow cytometry >0.77 increases the risk of developing disease ( 11 ). Use of condoms are advised for people with HTLV-1 to reduce the likelihood of sexual transmission between serodiscordant couples.…”

Section: Introductionmentioning

confidence: 99%

Cabotegravir, the Long-Acting Integrase Strand Transfer Inhibitor, Potently Inhibits Human T-Cell Lymphotropic Virus Type 1 Transmission in vitro

2022

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Human T-cell lymphotropic virus type 1 (HTLV-1) is a deltaretrovirus most prevalent in southwestern Japan, sub-Saharan Africa, Australia, South America, and the Caribbean. Latest figures approximate 10 million people worldwide to be infected with HTLV-1. This is likely a significant underestimation due to lack of screening in endemic areas and absence of seroconversion symptoms. The two primary diseases associated with HTLV-1 infection are adult T cell leukaemia-lymphoma, a malignant and, sometimes, aggressive cancer; and HTLV-1 associated myelopathy/tropical spastic paraparesis, a debilitating neurological degenerative disease. Unfortunately, despite the poor prognosis, there is currently no effective treatment for HTLV-1 infection. We previously showed that integrase strand transfer inhibitors (INSTIs) clinically used for human immunodeficiency virus type 1 (HIV-1) prophylaxis and treatment are also effective against HTLV-1 transmission in vitro. In 2021 a new INSTI, cabotegravir, was approved by the FDA for HIV-1 treatment. We thus set out to evaluate its efficacy against HTLV-1 infection in vitro. Strand transfer assays performed using recombinant HTLV-1 integrase treated with increasing concentrations of cabotegravir, effectively inhibited strand transfer activity, displaying an IC50 of 77.8 ± 22.4 nM. Furthermore, cabotegravir blocked HTLV-1 transmission in tissue culture; we determined an EC50 of 0.56 ± 0.26 nM, similar to bictegravir. Alu-PCR confirmed the block in integration. Thus, there are four INSTIs and one reverse transcriptase inhibitor approved by the FDA for HIV-1 treatment, that potently block HTLV-1 infection in vitro. This should strongly encourage the establishment of a new standard of HTLV-1 treatment – particularly for pre-exposure prophylaxis and prevention of mother-to-child transmission.

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Section: Introductionmentioning

confidence: 99%

Cabotegravir, the Long-Acting Integrase Strand Transfer Inhibitor, Potently Inhibits Human T-Cell Lymphotropic Virus Type 1 Transmission in vitro

2022

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“…A recent study developed and demonstrated the use of oligoclonality index (OCI)-Flow, which is another flow cytometry method to analyze HTLV-1-infected cells, based on the T-cell receptor (TCR) Vβ subunit diversity on T-cells infected with HTLV-1 (CD3+, CCR4+, and CD26− T cells) [ 27 ]. OCI-Flow appears to be more specific for identifying patients with ATL-like clones, compared with methods that evaluate CD7 downregulation to predict the development of ATL.…”

Section: Discussionmentioning

confidence: 99%

HAS-Flow May Be an Adequate Method for Evaluating Human T-Cell Leukemia Virus Type 1 Infected Cells in Human T-Cell Leukemia Virus Type 1-Positive Rheumatoid Arthritis Patients Receiving Antirheumatic Therapies: A Retrospective Cross-Sectional Observation Study

Umekita

Hashikura

Takaki

et al. 2023

Viruses

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The study aims to assess the usefulness of human T-cell leukemia virus type 1 (HTLV-1)-infected cell analysis using flow cytometry (HAS-Flow) as a monitoring method for adult T-cell leukemia (ATL) development in HTLV-1-positive patients with rheumatoid arthritis (RA) under treatment with antirheumatic therapies. A total of 13 HTLV-1-negative and 57 HTLV-1-positive RA patients participated in this study, which was used to collect clinical and laboratory data, including HAS-Flow and HTLV-1 proviral load (PVL), which were then compared between the two groups. CADM1 expression on CD4+ cells in peripheral blood (PB) was used to identify HTLV-1-infected cells. The population of CADM1+ CD4+ cells was significantly higher in HTLV-1-positive RA patients compared to HTLV-1-negative RA patients. The population of CADM1+ CD4+ cells was correlated with HTLV-1 PVL values. There were no antirheumatic therapies affecting both the expression of CADM1 on CD4+ cells and PVLs. Six HTLV-1-positive RA patients who indicated both high HTLV-1 PVL and a predominant pattern of CADM1+ CD7neg CD4+ cells in HAS-Flow can be classified as high-risk for ATL progression. HAS-Flow could be a useful method for monitoring high-risk HTLV-1-positive RA patients who are at risk of developing ATL during antirheumatic therapies.

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“…Cytometry-based monitoring of measurable residual disease, including the HTLV-1 analysis system (HAS-Flow) that we previously described, 33 might be promising. 33,34 In addition, 6 (7%) of 90 transplanted patients had refractory or relapsed CNS disease after allo-HCT. Novel strategies to enhance CNS prophylaxis might be explored.…”

Section: Discussionmentioning

confidence: 99%

Improved survival of patients with aggressive ATL by increased use of allo-HCT: a prospective observational study

Ito¹,

Nakano

Tanaka³

et al. 2021

Blood Advances

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Aggressive adult T-cell leukemia/lymphoma (ATL) is a hematological malignancy that is difficult to treat with chemotherapy alone, and allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy. We conducted a multicenter, prospective, observational study to clarify the treatment outcomes of aggressive ATL in the current era. Between 2015 and 2018, 113 patients aged 70 years or younger with newly diagnosed aggressive ATL were enrolled. The median age at diagnosis was 61 years old. Treatment outcomes were compared with those of 1,792 ATL patients diagnosed between 2000 and 2013 in our previous retrospective study. The inclusion criteria were the same in both studies. The prospective cohort demonstrated better overall survival (OS) than the retrospective cohort (2-year OS, 45% versus 29%, respectively; P<0.001), with a much higher proportion of patients receiving allo-HCT (80% versus 34%, respectively; P<0.001) and a shorter interval from diagnosis to allo-HCT (median, 128 versus 170 days, respectively; P<0.001). Among the 90 patients who received allo-HCT (cord blood, n=30; HLA-haploidentical related donors, n=20; other related donors, n=14; other unrelated donors, n=26), the 2-year probabilities of OS, non-relapse mortality (NRM), and disease progression were 44%, 23%, and 46%, respectively. OS and NRM did not differ statistically according to donor type. Our results suggest that increased application of allo-HCT improved the survival of patients with aggressive ATL. The use of cord blood or HLA-haploidentical donors may be feasible for aggressive ATL when HLA-matched related donors are unavailable. This study was registered with the UMIN Clinical Trials Registry (UMIN 000017672).

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Quantification of T cell clonality in human T cell leukaemia virus type-1 carriers can detect the development of adult T cell leukaemia early

Cited by 13 publications

References 26 publications

Cabotegravir, the Long-Acting Integrase Strand Transfer Inhibitor, Potently Inhibits Human T-Cell Lymphotropic Virus Type 1 Transmission in vitro

Cabotegravir, the Long-Acting Integrase Strand Transfer Inhibitor, Potently Inhibits Human T-Cell Lymphotropic Virus Type 1 Transmission in vitro

HAS-Flow May Be an Adequate Method for Evaluating Human T-Cell Leukemia Virus Type 1 Infected Cells in Human T-Cell Leukemia Virus Type 1-Positive Rheumatoid Arthritis Patients Receiving Antirheumatic Therapies: A Retrospective Cross-Sectional Observation Study

Improved survival of patients with aggressive ATL by increased use of allo-HCT: a prospective observational study

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