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      Clinical features and treatment outcomes of opportunistic infections among human T-lymphotrophic virus type 1 (HTLV-1) carriers and patients with adult T-cell leukemia-lymphoma (ATL) at a single institution from 2006 to 2016

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          Abstract

          As opportunistic infections among human T-lymphotrophic virus type 1 (HTLV-1) carriers and patients with adult T-cell leukemia/lymphoma (ATL) pose a serious problem, it is necessary to clarify their clinical characteristics and outcomes in these patients. We retrospectively analyzed the clinical features and outcomes of opportunistic infections in 127 HTLV-1 carriers and 153 ATL patients between 2006 and 2016. The cumulative incidence rates of opportunistic infections among HTLV-1 carriers and ATL patients were 1.5% (2/127) and 6.5% (10/153), respectively. The etiology of opportunistic infections was as follows: fungal infections (3 cases), pneumocystis pneumonia, and cytomegalovirus (CMV) infections. Even after aggressive treatment, the prognosis of opportunistic infections was poor (50% of overall survival at 28 days). Regarding prognostic factors affecting the OS of opportunistic infections, higher SOFA scores (especially the respiratory subscore) and higher LDH values were identified by univariate analysis. Moreover, 3 out of 6 patients achieved spontaneous remission of ATL as the short-term outcome after the development of opportunistic infection. However, 5 out of 6 surviving patients exhibited ATL progression or relapse after a median of 194 days (133–226) after contracting an opportunistic infection as the long-term outcome of ATL. In conclusion, opportunistic infections should be carefully followed among HTLV-1 carriers and ATL patients because of their aggressive clinical course and poor outcomes. Furthermore, early diagnosis and subsequent prompt treatment are necessary in clinical practice.

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          Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma.

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            Impaired production of naive T lymphocytes in human T-cell leukemia virus type I-infected individuals: its implications in the immunodeficient state.

            Opportunistic infections frequently occur in patients with adult T-cell leukemia (ATL) and human T-cell leukemia virus type I (HTLV-I) carriers. However, the underlying mechanisms of such infections remain unknown. To clarify the mechanism of immunodeficiency in those infected with HTLV-I, this study analyzed the T-cell subsets in HTLV-I carriers and patients with HTLV-I-associated myelopathy/tropical spastic paraparesis and ATL using 3-color fluorescence with CD62L and CD45RA coexpression either with CD4(+) or CD8(+) T cells. The number of naive T lymphocytes was markedly suppressed in patients with ATL, particularly in those with acute form, compared with uninfected control individuals. The number of naive T cells was low in HTLV-I-infected individuals under 50 years old compared with uninfected individuals, whereas the number of memory T lymphocytes was greater in HTLV-I-infected individuals. Although the increase of memory T lymphocytes correlated with HTLV-I provirus loads, no relationship was found between naive T-cell counts and provirus loads. T-cell receptor rearrangement excision circles (TRECs), which are generated by DNA recombination during early T lymphopoiesis, were quantified to evaluate thymic function in HTLV-I-infected individuals. TREC levels were lower in HTLV-I-infected individuals than in uninfected individuals. In HTLV-I carriers less than 70 years old, an increase of Epstein-Barr virus DNA in peripheral blood mononuclear cells was observed in 6 of 16 (38%) examined, whereas it was detectable in only 1 of 11 uninfected controls. These results suggested that the low number of naive T lymphocytes was due to suppressed production of T lymphocytes in the thymus, which might account for immunodeficiency observed in HTLV-I-infected individuals.
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              Opportunistic Infections in Patients with HTLV-1 Infection

              As an acquired immunodeficiency, human immunodeficiency virus (HIV) infection is primarily responsible for opportunistic infections in infected patients. However, opportunistic infections also occur in individuals with human T cell lymphotrophic virus type 1 (HTLV-1) infection. Here, we report opportunistic infections in two Japanese HTLV-1-seropositive patients. The first patient was a 67-year-old male, who had cytomegalovirus infection associated with esophagogastritis and terminal ileitis. The patient was HTLV-1-positive and was diagnosed with smoldering adult T cell leukemia (ATL). High levels of serum soluble IL-2 receptor (sIL-2R; 4,304 U/mL) and an increased percentage of CD4+CD25+ T cells (75.5%) in peripheral blood were also detected. The second patient was a 78-year-old female, a known asymptomatic HTLV-1 carrier, who presented with persistent herpes zoster, followed by Pneumocystis jirovecii pneumonia. Disease progression of smoldering ATL along opportunistic infections was observed with very high levels of serum sIL-2R (14,058 U/mL) and an increased percentage of CD4+CD25+ T cells (87.2%) in peripheral blood. In patients with suspected opportunistic infections, both HTLV-1 and HIV should be considered. In HTLV-1-positive patients, an increase in the CD4+CD25+ T cell subset may have its value as a prognostic marker.
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                Author and article information

                Journal
                J Clin Exp Hematop
                J Clin Exp Hematop
                jslrt
                Journal of Clinical and Experimental Hematopathology : JCEH
                JSLRT
                1346-4280
                1880-9952
                22 December 2019
                December 2019
                : 59
                : 4
                : 156-167
                Affiliations
                Department of Internal Medicine, Miyazaki Prefectural Miyazaki Hospital , Miyazaki, Japan, Department of Psychiatry, Jozan Hospital , Kumamoto, Japan, Division of Gastroenterology and Hematology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki , Miyazaki, Japan, Trauma and Critical Care Center, Faculty of Medicine, University of Miyazaki , Miyazaki, Japan, Department of Pathology, Miyazaki Prefectural Miyazaki Hospital , Miyazaki, Japan, Department of Hematology, Hokkaido University Faculty of Medicine , Sapporo, Hokkaido, Japan
                Author notes
                Corresponding author: Dr. Noriaki Kawano, Department of Internal Medicine, Miyazaki Prefectural Miyazaki Hospital, 5-30 Kitatakamatsu, Miyazaki 880-8510, Japan., E-mail: kawanoriaki@ 123456yahoo.co.jp
                Article
                18032
                10.3960/jslrt.18032
                6954174
                31866618
                517151af-7e13-4874-933a-a0738b43ba41
                © 2019 by The Japanese Society for Lymphoreticular Tissue Research

                This is an open-access article distributed under the terms of the Creative Commons Attribution ShareAlike (CC BY-NC-SA) 4.0 License.

                History
                : 30 August 2018
                : 10 September 2019
                : 14 October 2019
                Categories
                Original Article

                adult t-cell leukemia/lymphoma,htlv-1 carrier,opportunistic infection,spontaneous remission of atl,progression of atl

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