scholarly journals Dichotomy in Fatal Outcomes in a Large Cohort of People Living with HTLV-1 in São Paulo, Brazil

Pathogens ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 25 ◽  
Author(s):  
Rosa Maria N. Marcusso ◽  
Johan Van Weyenbergh ◽  
João Victor Luisi de Moura ◽  
Flávia Esper Dahy ◽  
Aline de Moura Brasil Matos ◽  
...  
Keyword(s):  
T Cell ◽  
Cause Of Death ◽  
Clinical Care ◽  
Laboratory Data ◽  
Sao Paulo ◽  
São Paulo ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Associated Diseases

Background: Despite its relatively low incidence of associated diseases, Human T-cell Leukemia Virus-1 (HTLV-1) infection was reported to carry a significant risk of mortality in several endemic areas. HTLV-1-associated diseases, adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraperesis (HAM/TSP), as well as frequent coinfections with human immunodeficiency virus (HIV), hepatitis C virus (HCV), and Strongyloides stercoralis were associated to increased morbidity and mortality of HTLV-1 infection. Objective: To determine the mortality rate and its associated variables from an open cohort started in July 1997 at the HTLV Clinic, Emilio Ribas Institute (IIER), a major infectious disease hospital in São Paulo, Brazil. Methods: Since inception up to September 2018, we admitted 727 HTLV-1-infected individuals, with a rate of 30–50 new admissions per year. All patient data, including clinical and laboratory data, were regularly updated throughout the 21-year period, using a dedicated REDCap database. The Ethical Board of IIER approved the protocol. Results: During 21 years of clinical care to people living with HTLV-1 in the São Paulo region, we recruited 479 asymptomatic HTLV-1-infected individuals and 248 HAM/TSP patients, of which 632 remained under active follow-up. During a total of 3800 person-years of follow-up (maximum follow-up 21.5 years, mean follow-up 6.0 years), 27 individuals died (median age of 51.5 years), of which 12 were asymptomatic, one ATLL patient and 14 HAM/TSP patients. HAM/TSP diagnosis (but neither age nor gender) was a significant predictor of increased mortality by univariate and multivariate (hazard ratio (HR) 5.03, 95% CI [1.96–12.91], p = 0.001) Cox regression models. Coinfection with HIV/HCV was an independent predictor of increased mortality (HR 15.08; 95% CI [5.50–41.32]; p < 0.001), with AIDS-related infections as a more frequent cause of death in asymptomatics (6/13; p = 0.033). HIV/HCV-negative fatal HAM/TSP cases were all female, with urinary tract infection and decubitus ulcer-associated sepsis as the main cause of death (8/14, p = 0.002). Conclusions: All-cause mortality among people living with HTLV-1 in São Paulo differs between asymptomatic (2.9%) and HAM/TSP patients (7.3%), independent of age and gender. We observe a dichotomy in fatal cases, with HAM/TSP and HIV/HCV coinfection as independent risk factors for death. Our findings reveal an urgent need for public health actions, as the major causes of death, infections secondary to decubitus ulcers, and immune deficiency syndrome (AIDS)-related infections, can be targeted by preventive measures.

scholarly journals Coinfection by Strongyloides stercoralis in blood donors infected with human T-cell leukemia/lymphoma virus type 1 in São Paulo city, Brazil

2000 ◽  
Vol 95 (5) ◽  
pp. 711-712 ◽  
Author(s):  
Pedro P Chieffi ◽  
Carlos S Chiattone ◽  
Elder N Feltrim ◽  
Rita CS Alves ◽  
Maria A Paschoalotti
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Blood Donors ◽  
Strongyloides Stercoralis ◽  
Sao Paulo ◽  
São Paulo ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Human T Cell

scholarly journals Adult T-Cell Leukemia/Lymphoma: A Clinical and Epidemiological Analysis at the Medicine School of Sao Paulo University

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5091-5091
Author(s):  
Ana Costa Cordeiro ◽  
Luis Alberto de Padua Covas Lage ◽  
Renata Oliveira Costa ◽  
Debora Levy ◽  
Juliana Pereira
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Sao Paulo ◽  
Cell Leukaemia ◽  
São Paulo ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
First Line ◽  
Adult T Cell Leukemia ◽  
Average Survival

Abstract Background: Adult T-cell leukemia/lymphoma (ATLL) is a rare disease described in Japan in 1977 and associated with human T-cell leukemia virus 1 (HTLV-1) infection. It is classified into four subgroups [1]: smoldering and chronic forms which are considered indolent and acute and lymphoma subtypes that present an aggressive behavior and short overall survival (OS) despite the treatment. Here, we describe an ATLL experience at a reference cancer treatment institution in Sao Paulo, Brazil. Methods: We retrospectively analyzed 29 ATLL patients who were attended from June/2006 to June/2015 at the Medicine School of Sao Paulo University, Brazil. ATLL was classified according to Shimoyama criteria [1] and Levine score [2] was used to estimate the probability of ATLL diagnosis. All patients were HTLV-1+. In the leukemic subtypes of ATLL, the neoplastic cells were CD3+/CD4+/CD8- or CD3+/CD4-/CD8- along with CD25+ and lack of CD7 expression. In the lymphoma type all patients showed a peripheral T cell lymphoma on their tissue biopsy. Statistical analysis was performed using GraphPad Prism Version 5.0 software. Results: Table 1 shows the clinical characteristics of patients on diagnosis. Acute ATLL was associated with higher Levine's score. The average age on diagnosis was 48.82 years old (18.69-74.26). Our data is in accordance with previous Brazilian studies that showed lower average age on diagnosis. This could be related to earlier infection, intrinsic characteristics of virus strains circulating in Americas or host immune particularities. There was confection with B hepatitis, C hepatitis and HIV in three, two and one case, respectively. Forty-five per cent of the patients had skin lesions and eight patients presented central nervous system disease (4 of acute ATLL). No patient had concomitant HTLV-I-Associated Myelopathy/Tropical Spastic Paraparesis. In our practice, smoldering ATLL was usually held in a watchfull-waiting approach. All six chronic ATLL patients were treated with interferon alpha and zidovudine (IFN+AZT) first-line. Progression-free survival (PFS) was 36.06 months and 12.4 months for smoldering and chronic subtypes, respectively. Acute and lymphoma subtypes had been treated with polichemotherapy, usually with CHOEP regimen (vincristine 1,4 mg/m2 i.v D1, doxorubicin 50mg/m2 i.v D1, cyclophosphamide 750mg/m2 i.v D1, etoposide 750 mg/m2 i.v D1, dexamethasone 20 mg i.v on day 1, prednisone 100 mg days 2 to 5) first-line. Overall average survival for lymphoma ATLL was 11.57 months, shorter than previous reports (average of 16 months, 86% treated with CHOP regimen [3]; survival of 19.7 months LSG15 protocol [4]). Eleven in 15 patients with acute ATLL had died after an average of 8.5 months (2.3 - 15.5) after the diagnosis. Overall survival for all subtypes was 15.17months (fig 1A), and 59.03; 44.47; 11.75 and 5.8 months (p= 0.0634) for smoldering, chronic, lymphoma and acute subtypes, respectively (fig 1B). Conclusion: We found an OS of 5.8 months for acute ATLL treated with chemotherapy as first-line, which is comparable to literature (average survival of 6 months [3]) but shorter than those patients treated with first-line IFN+AZT (average survival of 9 months [3]). In our setting it is still scarcely available trioxide arsenic and clinical trials for ATLL, and allogenic transplant related to mortality is still high. We are therefore changing our practice according to recent recommendations and aiming to treat leukemic ATLL first-line with higher tolerated doses of IFN+AZT to improve our survival curve. References 1. Shimoyama M. Diagnostic criteria and classification of clinical subtypes of adultT-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87). Br J Haematol. 1991; 79(3):428-37. 2. Levine PH, et al. AdultT-cell leukemia/lymphoma: a working point-score classification for epidemiological studies. Int J Cancer. 1994; 59(4):491-3. 3. Bazarbachi A, et al. Meta-analysis on the use of zidovudine and interferon alfa in adult t cell leukemia/lymphoma showing improved survival in the leukemic subtypes. J Clin Oncol 2010; 28(27):4177-83. 4. Yamada Y, et al. A new gcsf supported combination chemotherapy LSG15, for adult T-Cell leukaemia -lymphoma: japan clinical oncology group study 9303. Br J Haematol 2001; 113(2):375-82. Table 1. Patient characteristics at diagnosis Table 1. Patient characteristics at diagnosis Figure 1. Overall survival for all casuistic (A) and for each subtype of ATLL patients (B). Figure 1. Overall survival for all casuistic (A) and for each subtype of ATLL patients (B). Disclosures No relevant conflicts of interest to declare.

scholarly journals Cytokine Networks Dysregulation during HTLV-1 Infection and Associated Diseases

Viruses ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 691 ◽  
Author(s):  
Nicolas Futsch ◽  
Gabriela Prates ◽  
Renaud Mahieux ◽  
Jorge Casseb ◽  
Hélène Dutartre
Keyword(s):  
T Cell ◽  
Immune Escape ◽  
Leukemia Virus ◽  
Spastic Paraparesis ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Associated Diseases ◽  
Cytokines And Chemokines ◽  
Human T Cell

Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of a neural chronic inflammation, called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and of a malignant lymphoproliferation, called the adult T-cell leukemia/lymphoma (ATLL). The mechanisms through which the HTLV-1 induces these diseases are still unclear, but they might rely on immune alterations. HAM/TSP is associated with an impaired production of pro-inflammatory cytokines and chemokines, such as IFN-γ, TNF-α, CXCL9, or CXCL10. ATLL is associated with high levels of IL-10 and TGF-β. These immunosuppressive cytokines could promote a protumoral micro-environment. Moreover, HTLV-1 infection impairs the IFN-I production and signaling, and favors the IL-2, IL-4, and IL-6 expression. This contributes both to immune escape and to infected cells proliferation. Here, we review the landscape of cytokine dysregulations induced by HTLV-1 infection and the role of these cytokines in the HTLV-1-associated diseases progression.

scholarly journals Adult T-cell leukemia/lymphoma incidence rate in French Guiana: a prospective cohort of women infected with HTLV-1

2020 ◽  
Vol 4 (9) ◽  
pp. 2044-2048 ◽  
Author(s):  
Jill-Léa Ramassamy ◽  
Patricia Tortevoye ◽  
Balthazar Ntab ◽  
Béatrice Seve ◽  
Gabriel Carles ◽  
...  
Keyword(s):  
T Cell ◽  
South America ◽  
Incidence Rate ◽  
Prospective Cohort ◽  
French Guiana ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
Incident Cases

Abstract Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy caused by the human T-cell leukemia virus type 1 (HTLV-1). The incidence of ATL among HTLV-1 carriers remains largely unknown in endemic countries other than Japan as very few prospective studies have been performed. We assessed the ATL incidence rate among HTLV-1 infected women in a prospective cohort in French Guiana. This is the first prospective study to assess the ATL incidence rate in an area of South America where HTLV-1 prevalence is high. Patients were enrolled between 1991 and 2005, and follow-up continued until April 2018. In the general hospital in Saint-Laurent-du-Maroni, 307 pregnant women were diagnosed with HTLV-1 infection, and 268 of them were observed for a median of 16.7 years. During follow-up, 9 ATL incident cases occurred resulting in an ATL incidence rate of 2.03 per 1000 HTLV-1 carrier-years (95% confidence interval, 0.93-3.85 per 1000 HTLV-1 carrier-years). The median age at diagnosis was 47.4 years, and median survival from diagnosis was low at 3.5 months. The ATL incidence rate was elevated for a study population consisting mostly of young people, which could either be a general feature in South America or could be specific to the Noir Marron population that constituted most of the cohort.

scholarly journals Modified LSA2-L2 treatment in 53 children with E-rosette-positive T- cell leukemia: results and prognostic factors (a Pediatric Oncology Group Study)

Blood ◽  
1982 ◽  
Vol 60 (5) ◽  
pp. 1159-1168 ◽  
Author(s):  
DJ Pullen ◽  
MP Sullivan ◽  
JM Falletta ◽  
JM Boyett ◽  
GB Humphrey ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Oncology Group ◽  
Table Analysis ◽  
Pediatric Oncology Group ◽  
Group Sex ◽  
Prognosis Indicator

Abstract In an attempt to improve the poor outlook for children with T-cell leukemia (T-ALL), the Southwest Oncology Group, Pediatric Division, used a modified LSA2-L2 multidrug regimen to treat 53 patients with E- rosette-positive T-ALL. This regimen was chosen because of its demonstrated efficacy in T-cell (mediastinal) non-Hodgkin's lymphoma. Complete remission (CR) rate was 88%. Range of follow-up for those patients remaining in CR is 24–49 mo (median 39 mo). Life table analysis estimates that 40% (SE 8.3%) of all patients who started induction therapy will remain failure-free at 3 yr. For patients achieving CR, 46% (SE 9%) are projected to remain in both marrow and extramedullary CR at 3 yr. Median failure-free duration was 13 mo, but only 1 patient has relapsed beyond 16 mo. Twenty-nine percent of initial relapses were isolated CNS relapses. The following presenting factors did not relate significantly to outcome: hemoglobin, platelet count, uric acid, race, and mediastinal mass. Age greater than 10 yr was a poor prognosis indicator only in the less than 50,000/microliter WBC group. Sex was not a significant factor after adjusting for WBC. WBC was the most important prognostic factor: 19% (SE 8%) of patients with WBC greater than 50,000/microliter are projected to remain failure- free at 3 yr as compared to 67% (SE 11%) of patients with WBC less than 50,000/microliter. Although the overall results are better than those previously reported for pediatric patients with T-ALL, the long-term failure-free rate remains low for patients presenting with greater than 50,000/microliter WBC.

scholarly journals An extremely indolent T-cell leukemia: an 18-year follow-up

2016 ◽  
pp. 76-78 ◽  
Author(s):  
Samuel Adediran ◽  
Dennis Cornfield ◽  
Adam Bagg ◽  
Nicole Agostino
Keyword(s):  
T Cell ◽  
T Cell Leukemia ◽  
Cell Leukemia

scholarly journals Mogamulizumab for relapsed adult T‐cell leukemia–lymphoma: Updated follow‐up analysis of phase I and II studies

2017 ◽  
Vol 108 (10) ◽  
pp. 2022-2029 ◽  
Author(s):  
Takashi Ishida ◽  
Atae Utsunomiya ◽  
Tatsuro Jo ◽  
Kazuhito Yamamoto ◽  
Koji Kato ◽  
...  
Keyword(s):  
T Cell ◽  
Phase I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
Phase I And Ii

scholarly journals Efficient horizontal transmission without viral super-spreaders may cause the high prevalence of STLV-1 infection in Japanese macaques

2019 ◽  
Author(s):  
Megumi Murata ◽  
Jun-ichirou Yasunaga ◽  
Ayaka Washizaki ◽  
Yohei Seki ◽  
Wei Keat Tan ◽  
...  
Keyword(s):  
T Cell ◽  
Leukemia Virus ◽  
Horizontal Transmission ◽  
Japanese Macaques ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
High Prevalence ◽  
T Cell Leukemia Virus

AbstractsSimian T-cell leukemia virus type-1 (STLV-1) is disseminated among various non-human primate species and is closely related to human T-cell leukemia virus type-1 (HTLV-1), the causative agent of adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. Notably, the prevalence of STLV-1 infection in Japanese macaques (JMs) is estimated to be much greater than that in other non-human primates; however, the mechanism and mode of STLV-1 transmission remain unknown. We hypothesized that a substantial proportion of infected macaques may play a critical role as viral super-spreaders for efficient inter-individual transmission leading to the high prevalence of infection. To address this, we examined a cohort of 280 JMs reared in a free-range facility for levels of anti-STLV-1 antibody titers (ABTs) and STLV-1 proviral loads (PVLs). We found that the prevalence of STLV-1 in the cohort reached up to 65% (180/280), however, the ABTs and PVLs were normally distributed with mean values of 4076 and 0.62%, respectively, which were comparable to those of HTLV-1-infected humans. Contrary to our expectations, we did not observe the macaques with abnormally high PVLs and poor ABTs, and therefore, the possibility of viral super-spreaders was unlikely. Results from further analyses regarding age-dependent changes in STLV-1 prevalence and a longitudinal follow-up of STLV-1 seroconversion strongly suggest that frequent horizontal transmission is a major route of STLV-1 infection, probably due to the unique social ecology of JMs associated with environmental adaptation.ImportanceWe investigated the cause of the high prevalence of STLV-1 infection in the studied JMs cohort. Contrary to our expectations, the potential viral super-spreaders as shown by abnormally high PVLs and poor ABTs were not observed among the JMs. Rather, the ABTs and PVLs among the infected JMs were comparable to those of HTLV-1-infected humans although the prevalence of HTLV-1 in humans is much less than the macaques. Further analyses demonstrate that the prevalence drastically increased over one year of age and most of these animals over 6 years of age were infected with STLV-1, and that in the longitudinal follow-up study frequent seroconversion occurred in not only infants but also in juvenile and adult seronegative monkeys (around 20% per year). This is the first report showing that frequent horizontal transmission without viral super-spreaders may cause high prevalence of STLV-1 infection in JMs.

scholarly journals HTLV-1 Infection and Pathogenesis: New Insights from Cellular and Animal Models

2021 ◽  
Vol 22 (15) ◽  
pp. 8001
Author(s):  
Greta Forlani ◽  
Mariam Shallak ◽  
Roberto Sergio Accolla ◽  
Maria Grazia Romanelli
Keyword(s):  
T Cell ◽  
Animal Models ◽  
Spastic Paraparesis ◽  
Experimental Models ◽  
T Cell Leukemia ◽  
Cell Models ◽  
Cell Leukemia ◽  
Associated Diseases ◽  
Human T Cell

Since the discovery of the human T-cell leukemia virus-1 (HTLV-1), cellular and animal models have provided invaluable contributions in the knowledge of viral infection, transmission and progression of HTLV-associated diseases. HTLV-1 is the causative agent of the aggressive adult T-cell leukemia/lymphoma and inflammatory diseases such as the HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Cell models contribute to defining the role of HTLV proteins, as well as the mechanisms of cell-to-cell transmission of the virus. Otherwise, selected and engineered animal models are currently applied to recapitulate in vivo the HTLV-1 associated pathogenesis and to verify the effectiveness of viral therapy and host immune response. Here we review the current cell models for studying virus–host interaction, cellular restriction factors and cell pathway deregulation mediated by HTLV products. We recapitulate the most effective animal models applied to investigate the pathogenesis of HTLV-1-associated diseases such as transgenic and humanized mice, rabbit and monkey models. Finally, we summarize the studies on STLV and BLV, two closely related HTLV-1 viruses in animals. The most recent anticancer and HAM/TSP therapies are also discussed in view of the most reliable experimental models that may accelerate the translation from the experimental findings to effective therapies in infected patients.

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