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1.
J Clin Virol ; 167: 105578, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37660433

RESUMO

BACKGROUND: HTLV-1 infection is a neglected disease, despite producing neurological and lymphoproliferative severe illnesses and affect over 10 million people worldwide. Roughly 5% of HTLV-1 carriers develop Adult T-cell leukemia/lymphoma (ATLL), one of the most aggressive hematological malignancies. METHODS: A national HTLV-1 register exists since 1989 in Spain, a non-endemic country with a large migrant flow from Latin America and Equatorial Africa, where HTLV-1 is endemic. The main features of all patients diagnosed with ATLL in Spain up to date are reported. RESULTS: A total of 451 cases of HTLV-1 infection had been reported in Spain until the end of year 2022. ATLL had been diagnosed in 35 (7.8%). The current average incidence of ATLL in Spain is of two cases per year. Women represent 57% of ATLL patients. Mean age at diagnosis was 47 years-old. Roughly 57% were Latin Americans and 26% Africans. At diagnosis, the majority presented with acute or lymphoma clinical forms. Survival was shorter than one year in most of them. Mean HTLV-1 proviral load was significantly greater in ATLL patients than in asymptomatic HTLV-1 carriers (2,305 vs 104 copies/104 PBMC). HTLV-1 subtyping in 6 ATLL patients found the 1a transcontinental variant (n = 4) and the Japanese variant (n = 2). All ATLL patients were negative for HIV-1, did not develop HTLV-1-associated myelopathy and were not transplant recipients. CONCLUSION: The rate of ATLL is very low in Spain and mostly associated to migrants from HTLV-1 endemic regions. Given the poor clinical outcome of ATLL, HTLV-1 testing should be performed at least once in all migrants coming from HTLV-1 endemic countries and in natives who have lived in or had sex partners from such regions.


Assuntos
Vírus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T do Adulto , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , População Africana , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Leucócitos Mononucleares , Espanha
2.
Front Cell Infect Microbiol ; 13: 1164526, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37293205

RESUMO

Background: Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus known to cause two major diseases: adult T-cell leukemia/lymphoma and a progressive neuromyelopathy-tropical spastic paraparesis. Many viruses may be involved in the pathogenesis of thyroiditis; however, few studies have focused on the role of HTLV-1. We aimed to investigate the association between HTLV-1 and biological thyroid dysfunction. Methods: We included 357 patients with a positive HTLV-1 serology and thyroid-stimulating hormone assay data between 2012 and 2021 in a hospital in French Guiana; we compared the prevalence of hypothyroidism and hyperthyroidism in this group with that in an HTLV-1-negative control group (722 persons) matched for sex and age. Results: The prevalence of hypothyroidism and hyperthyroidism in patients with HTLV-1 infection was significantly higher than that in the control group (11% versus 3.2% and 11.3% versus 2.3%, respectively; p < 0.001). Conclusion: Our study shows, for the first time, the association between HTLV-1 and dysthyroidism in a large sample, suggesting that thyroid function exploration should be systematically implemented in this population as this may have an impact on therapeutic management.


Assuntos
Vírus Linfotrópico T Tipo 1 Humano , Hipertireoidismo , Hipotireoidismo , Leucemia-Linfoma de Células T do Adulto , Adulto , Humanos , Hipertireoidismo/complicações , Hipertireoidismo/epidemiologia , Hipertireoidismo/virologia , Hipotireoidismo/complicações , Hipotireoidismo/epidemiologia , Hipotireoidismo/virologia , Leucemia-Linfoma de Células T do Adulto/complicações , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Masculino , Feminino , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Estudos de Casos e Controles , Guiana Francesa/epidemiologia , Prevalência
3.
JCO Glob Oncol ; 9: e2200369, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36921240

RESUMO

PURPOSE: Human T-lymphotropic virus type 1 (HTLV-1) is an endemic virus in Latin America that is directly linked to adult T-cell leukemia/lymphoma (ATL). Previous studies have suggested an oncogenic role of HTLV-1 in non-ATL neoplasms and have found higher mortality in HTLV-1 carriers without ATL. METHODS: In this retrospective cohort study, HTLV-1 carriers were identified through screening at a tertiary cancer center between 2006 and 2019. We compared the overall survival (OS) outcomes of patients with ATL with those with other solid or hematologic malignancies by sex stratification. RESULTS: We identified 1,934 HTLV-1 carriers diagnosed with cancer. The median age at diagnosis was 62 (range 20-114) years, 76% were female, 60% had no or elementary school education, and 50% were born in the Andean highlands. The most common non-ATL neoplasm was cervical cancer (50%) among females and non-ATL non-Hodgkin lymphoma (26%) among males. With a median follow-up of 66 months, the 5-year OS of HTLV-1 carriers with non-ATL neoplasms (26%-47% for females and 22%-34% for males) was inferior to those reported in the general population. As expected, patients with ATL had a worse prognosis (5-year OS: 10% for females and 8% for males). CONCLUSION: HTLV-1 carriers with cancer were middle age and from underprivileged settings, suggesting an undetected transmission among vulnerable populations, especially females. Survival estimates of HTLV-1 carriers with non-ATL neoplasms were lower than the regional outcomes. Future research should ascertain how the biology of HTLV-1 and health care disparities affect the outcomes of HTLV-1 carriers, as well as determine the burden of HTLV-1 infection in the cancer population to recommend screening in the outpatient setting of endemic regions.


Assuntos
Vírus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T do Adulto , Linfoma não Hodgkin , Neoplasias do Colo do Útero , Masculino , Pessoa de Meia-Idade , Adulto , Humanos , Feminino , Adulto Jovem , Idoso , Idoso de 80 Anos ou mais , Vírus Linfotrópico T Tipo 1 Humano/genética , Estudos Retrospectivos , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Leucemia-Linfoma de Células T do Adulto/epidemiologia
4.
Leuk Lymphoma ; 64(4): 865-873, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36772789

RESUMO

Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-cell leukemia virus type-I (HTLV-1). This study investigated whether the number of newly diagnosed patients with ATL is decreasing in the background of a declining number of individuals infected by HTLV-1 in Kagoshima, Japan, one of the most endemic areas of HTLV-1 in the world. We retrospectively analyzed the number of newly diagnosed patients with ATL between January 2001 and December 2021 in three major hospitals. The number of newly diagnosed patients with B-cell non-Hodgkin lymphoma (B-NHL) in the same period was examined as an internal control. One thousand eighteen and 2,029 patients with ATL and B-NHL were registered, respectively. The age-adjusted incidence of ATL steadily increased between 2001 and 2012, whereas that between 2013 and 2021 decreased. Despite the limitation of its retrospective nature, this is the first report indicating a decrease in ATL patients in Japan.


Assuntos
Vírus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T do Adulto , Linfoma , Adulto , Humanos , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Estudos Retrospectivos , Japão/epidemiologia , Linfoma/complicações
5.
Sex Transm Infect ; 99(1): 50-52, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35523573

RESUMO

OBJECTIVES: Human T-cell leukaemia virus type 1 (HTLV-1), an STI, is reported to be highly prevalent in Indigenous communities in Central Australia. HTLV-1 is an incurable, chronic infection which can cause Adult T-cell leukaemia/lymphoma (ATL). ATL is associated with high morbidity and mortality, with limited treatment options. We studied the prevalence of HTLV-1 and ATL in the state of Queensland, Australia. METHODS: Serum samples stored at healthcare services in Brisbane, Townsville and Cairns and at haemodialysis units in Brisbane (2018-2019) were screened for HTLV-1/2 antibodies using the Abbott ARCHITECT chemiluminescent microparticle immunoassay (CMIA) for antibodies against gp46-I, gp46-II and GD21 (Abbott CMIA, ARCHITECT). Reactive samples were confirmed through Western blot. Pooled Australian National Cancer Registry surveillance data reporting on cases coded for ATL (2004-2015) were analysed. RESULTS: Two out of 2000 hospital and health services samples were confirmed HTLV-1-positive (0.1%, 95% CI 0.02% to 0.4%), both in older women, one Indigenous and one non-Indigenous. All 540 haemodialysis samples tested negative for HTLV. All samples were HTLV-2-negative. Ten out of 42 (24.8%) reported cases of ATL in Australia were from Queensland (crude incidence rate 0.025/100 000; 95% CI 0.011 to 0.045); most cases were seen in adult men of non-Indigenous origin. Nineteen deaths due to ATL were recorded in Australia. CONCLUSION: We confirm that HTLV-1 and ATL were detected in Queensland in Indigenous and non-Indigenous people. These results highlight the need for HTLV-1 prevalence studies in populations at risk of STIs to allow the implementation of focused public health sexual and mother-to-child transmission prevention strategies.


Assuntos
Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T do Adulto , Linfoma , Masculino , Adulto , Humanos , Feminino , Idoso , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Estudos Transversais , Queensland/epidemiologia , Estudos Retrospectivos , Austrália/epidemiologia , Transmissão Vertical de Doenças Infecciosas , Infecções por HTLV-I/epidemiologia
6.
Viruses ; 14(7)2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35891440

RESUMO

Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The effects of HTLV-1 on health are not fully elucidated. Epidemiological studies have shown that the prevalence of HTLV-1 infection is high in patients with rheumatic diseases. The prevalence of comorbidities, such as Sjögren's syndrome and rheumatoid arthritis (RA), is higher in patients with HAM/TSP than the in general population. Studies have shown the effects of HTLV-1-infection on the clinical course of RA. Major questions on the association between HTLV-1 infection and RA: (1) Is it possible that HTLV-1 infection causes RA? (2) Do patients with RA who are infected with HTLV-1 have different clinical features? (3) Are immunosuppressants associated with an increased prevalence of HAM/TSP or ATL in RA patients with HTLV-1 infection? Is ATL an immunosuppressive therapy-associated lymphoproliferative disorder? No large-scale studies have investigated the incidence of ATL in patients with RA. However, several studies have reported the development of ATL in patients with RA who have HTLV-1 infection. This review aimed to shed light on the association between HTLV-1 infection and RA and summarize the unmet medical needs of RA patients with HTLV-1 infection.


Assuntos
Artrite Reumatoide , Vírus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T do Adulto , Paraparesia Espástica Tropical , Adulto , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Humanos , Leucemia-Linfoma de Células T do Adulto/complicações , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Paraparesia Espástica Tropical/epidemiologia , Prevalência
7.
Viruses ; 14(4)2022 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-35458521

RESUMO

Nationwide surveys of adult T-cell leukemia/lymphoma (ATL) have played an important role in helping us to understand the pathophysiology of this disease and analyze its prognosis in Japan. Classifications of clinical subtypes have been proposed based on the results of nationwide surveys of patients with ATL diagnosed in the 1980s. This article highlighted the classification and prognosis of ATL based on different surveys and focused on the comparison of data derived from the available surveys. The 11th nationwide hospital-based survey was conducted in patients with ATL diagnosed in 2010-2011 using the same method as that used in the 1980s survey. The median age of disease onset was 68 years, which was increased compared with previous surveys. While median survival of patients with the acute and lymphoma types had not improved much since the 1980s, the 4-year survival rate was higher. Little improvement in the prognosis was observed for the chronic and smoldering types. The 12th nationwide survey of patients with ATL diagnosed in 2012-2013 also showed an increase in age at onset. Further epidemiological research that includes more cases is needed to deepen our understanding of the actual state of treatment and prognosis of this disease.


Assuntos
Leucemia-Linfoma de Células T do Adulto , Linfoma , Adulto , Idoso , Hospitais , Humanos , Japão/epidemiologia , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Prognóstico
8.
Clin Microbiol Rev ; 35(2): e0007821, 2022 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-35195446

RESUMO

Human T-lymphotropic virus type 1 (HTLV-1) is estimated to affect 5 to 10 million people globally and can cause severe and potentially fatal disease, including adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The burden of HTLV-1 infection appears to be geographically concentrated, with high prevalence in discrete regions and populations. While most high-income countries have introduced HTLV-1 screening of blood donations, few other public health measures have been implemented to prevent infection or its consequences. Recent advocacy from concerned researchers, clinicians, and community members has emphasized the potential for improved prevention and management of HTLV-1 infection. Despite all that has been learned in the 4 decades following the discovery of HTLV-1, gaps in knowledge across clinical and public health aspects persist, impeding optimal control and prevention, as well as the development of policies and guidelines. Awareness of HTLV-1 among health care providers, communities, and affected individuals remains limited, even in countries of endemicity. This review provides a comprehensive overview on HTLV-1 epidemiology and on clinical and public health and highlights key areas for further research and collaboration to advance the health of people with and at risk of HTLV-1 infection.


Assuntos
Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T do Adulto , Paraparesia Espástica Tropical , Adulto , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/prevenção & controle , Humanos , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Paraparesia Espástica Tropical/epidemiologia , Paraparesia Espástica Tropical/patologia , Saúde Pública
9.
Rinsho Ketsueki ; 62(7): 760-765, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34349060

RESUMO

Adult T-cell leukemia-lymphoma (ATL) is a rare disease, and the nationwide surveys conducted in Japan have played an important role in improving our understanding of the clinical features and prognosis of this disease. The diagnostic criteria of clinical subtypes have been proposed based on the surveys conducted on patients with ATL who were diagnosed in the 1980s; the current treatment guideline in Japan is based on this classification of ATL subtypes. In the survey for patients diagnosed between 2000 and 2009, the usefulness of the clinical subtypes was confirmed, and soluble interleukin-2 receptor was identified as a new prognostic factor for chronic- and smoldering-type ATL. We conducted another survey for patients who were diagnosed in 2010 and 2011. The age at diagnosis was higher than that reported in previous trials, and the median patient age at diagnosis was 68 years in the study. The 4-year survival rate was better than that in previous studies on acute- and lymphoma-type disease; however, the prognosis has not improved in chronic- and smoldering-type disease. Further nationwide surveys are expected to improve the treatment strategies for ATL.


Assuntos
Leucemia-Linfoma de Células T do Adulto , Adulto , Humanos , Japão/epidemiologia , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Leucemia-Linfoma de Células T do Adulto/terapia , Prognóstico , Receptores de Interleucina-2 , Taxa de Sobrevida
10.
Cancer Sci ; 112(10): 4346-4354, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34355480

RESUMO

Adult T-cell leukemia-lymphoma (ATL) is a T-cell malignancy that is endemic to Japan. In this latest nationwide study of ATL, we collected the data from 4 nationwide registries of patients diagnosed in 2012-2013; the Hematology Blood Disease, the Skin Cancer Society, the Hospital-Based Cancer Registries, and information from the hospitals that participated in the Japanese nationwide survey of ATL in 2010-2011. In the present study, 2614 patients with ATL were diagnosed based on the registries, and 117 departments registered 1042 patients. Among these patients, 984 were eligible for analysis. The median age at diagnosis was 69 y. A larger proportion of patients with ATL older than 70 y was diagnosed with the lymphoma subtype, and more than half of the patients with ATL in the metropolitan areas were born in the human T-cell leukemia virus type I (HTLV-1)-endemic areas of Kyushu/Okinawa, which are almost identical to the findings in our 2010-2011 study. Additionally, we identified that patients with ATL migrated from the endemic areas for HTLV-1 to the non-endemic metropolitan areas. The present study was able to reduce the burden of searching each hospital and to update the clinico-epidemiological characteristics of a large number of patients with ATL in Japan, suggesting the usefulness and feasibility of the novel data collection method. The establishment of a more sophisticated database management system for ATL is necessary for future continuous surveys.


Assuntos
Leucemia-Linfoma de Células T do Adulto/epidemiologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais/estatística & dados numéricos , Emigração e Imigração/estatística & dados numéricos , Doenças Endêmicas , Feminino , Infecções por HTLV-I/epidemiologia , Inquéritos Epidemiológicos , Vírus Linfotrópico T Tipo 1 Humano , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Distribuição por Sexo , Fatores de Tempo
11.
JCO Glob Oncol ; 7: 1151-1166, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34270330

RESUMO

PURPOSE: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive disease caused by the human T-cell leukemia virus type 1. Real-world data of ATLL in Latin America are lacking. PATIENTS AND METHODS: We analyzed patients with ATLL (acute, lymphomatous, chronic, and smoldering) encountered in 11 Latin American countries between 1995 and 2019. Treatment response was assessed according to the 2009 consensus report. Survival curves were estimated using the Kaplan-Meier method and log-rank test. RESULTS: We identified 253 patients; 226 (lymphomatous: n = 122, acute: n = 73, chronic: n = 26, and smoldering: n = 5) had sufficient data for analysis (median age 57 years). Most patients with ATLL were from Peru (63%), Chile (17%), Argentina (8%), and Colombia (7%). Hypercalcemia was positively associated with acute type (57% v lymphomatous 27%, P = .014). The median survival times (months) were 4.3, 7.9, 21.1, and not reached for acute, lymphomatous, chronic, and smoldering forms, with 4-year survival rates of 8%, 22%, 40%, and 80%, respectively. First-line zidovudine (AZT)-interferon alfa (IFN) resulted in an overall response rate of 63% (complete response [CR] 24%) for acute. First-line chemotherapy yielded an overall response rate of 41% (CR 29%) for lymphomatous. CR rate was 42% for etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone versus 12% for cyclophosphamide, vincristine, doxorubicin, and prednisone-like regimen (P < .001). Progression-free survival at 1 year for acute type patients treated with AZT-IFN was 67%, whereas 2-year progression-free survival in lymphomatous type patients who achieved CR after chemotherapy was 77%. CONCLUSION: This study confirms Latin American ATLL presents at a younger age and has a high incidence of lymphomatous type, low incidence of indolent subtypes, and worse survival rates as compared with Japanese patients. In aggressive ATLL, chemotherapy remains the preferred choice for lymphomatous favoring etoposide-based regimen (etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone), whereas AZT-IFN remains a good first-line option for acute subtype.


Assuntos
Leucemia-Linfoma de Células T do Adulto , Linfoma , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Argentina , Chile , Colômbia , Humanos , América Latina/epidemiologia , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Pessoa de Meia-Idade , Peru/epidemiologia
12.
Blood Adv ; 4(9): 2044-2048, 2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32396612

RESUMO

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.


Assuntos
Vírus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T do Adulto , Adolescente , Adulto , Feminino , Guiana Francesa/epidemiologia , Humanos , Incidência , Japão , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Gravidez , Estudos Prospectivos
13.
Biol Blood Marrow Transplant ; 26(8): 1433-1438, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32417489

RESUMO

Adult T cell leukemia-lymphoma (ATL) is a mature T cell malignancy associated with human T cell leukemia virus type I (HTLV-1), a retrovirus that is endemic in southwestern Japan. Because of population migration, cases of ATL are expected to increase in nonendemic areas. Here, to clarify the outcomes of patients with ATL in the nonendemic metropolitan area of Osaka, we retrospectively analyzed data from the population-based Osaka Cancer Registry from 2010 to 2015. This analysis included 91 patients age ≤70 years who received chemotherapy for ATL. With a median follow-up of 988 days in surviving patients, the probability of 2-year overall survival (OS) was 21.9% (95% confidence interval [CI], 14.1% to 30.9%) and the median OS was 9.8 months (95% CI, 7.3 to 13.5 months). The probability of 2-year OS was 22.2% in the nontransplant group (n = 63) and 21.4% in the transplant group (n = 28), without a statistically significant difference between the 2 groups. Allogeneic transplantation was not a favorable prognostic factor in patients with ATL in propensity score-adjusted analysis (P = .86, log-rank test). More clinical studies are needed to improve the clinical outcomes of patients with ATL in nonendemic areas.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma de Células T do Adulto , Linfoma , Adulto , Idoso , Humanos , Japão/epidemiologia , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Leucemia-Linfoma de Células T do Adulto/terapia , Sistema de Registros , Estudos Retrospectivos , Taxa de Sobrevida
14.
Proc Natl Acad Sci U S A ; 117(21): 11685-11691, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32393644

RESUMO

Human T cell leukemia virus 1 (HTLV-1) causes the functionally debilitating disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) as well as adult T cell leukemia lymphoma (ATLL). Although there were concerns that the mortality of HAM/TSP could be affected by the development of ATLL, prospective evidence was lacking in this area. In this 5-y prospective cohort study, we determined the mortality, prevalence, and incidence of ATLL in 527 HAM/TSP patients. The standard mortality ratio of HAM/TSP patients was 2.25, and ATLL was one of the major causes of death (5/33 deaths). ATLL prevalence and incidence in these patients were 3.0% and 3.81 per 1,000 person-y, respectively. To identify patients at a high risk of developing ATLL, flow cytometry, Southern blotting, and targeted sequencing data were analyzed in a separate cohort of 218 HAM/TSP patients. In 17% of the HAM/TSP patients, we identified an increase in T cells positive for cell adhesion molecule 1 (CADM1), a marker for ATLL and HTLV-1-infected cells. Genomic analysis revealed that somatic mutations of HTLV-1-infected cells were seen in 90% of these cases and 11% of them had dominant clone and developed ATLL in the longitudinal observation. In this study, we were able to demonstrate the increased mortality in patients with HAM/TSP and a significant effect of ATLL on their prognosis. Having dominant clonal expansion of HTLV-1-infected cells with ATLL-associated somatic mutations may be important characteristics of patients with HAM/TSP who are at an increased risk of developing ATLL.


Assuntos
Leucemia-Linfoma de Células T do Adulto , Paraparesia Espástica Tropical , Idoso , Progressão da Doença , Feminino , Vírus Linfotrópico T Tipo 1 Humano , Humanos , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Leucemia-Linfoma de Células T do Adulto/patologia , Masculino , Paraparesia Espástica Tropical/diagnóstico , Paraparesia Espástica Tropical/epidemiologia , Paraparesia Espástica Tropical/mortalidade , Paraparesia Espástica Tropical/patologia , Prognóstico , Estudos Prospectivos
15.
Blood ; 135(23): 2023-2032, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32160278

RESUMO

Adult T-cell leukemia/lymphoma (ATL) is an aggressive hematological malignancy caused by human T-cell leukemia virus type-1 (HTLV-1). ATL is preceded by decades of chronic HTLV-1 infection, and the tumors carry both somatic mutations and proviral DNA integrated into the tumor genome. In order to gain insight into the oncogenic process, we used targeted sequencing to track the evolution of the malignant clone in 6 individuals, 2 to 10 years before the diagnosis of ATL. Clones of premalignant HTLV-1-infected cells bearing known driver mutations were detected in the blood up to 10 years before individuals developed acute and lymphoma subtype ATL. Six months before diagnosis, the total number and variant allele fraction of mutations increased in the blood. Peripheral blood mononuclear cells from premalignant cases (1 year prediagnosis) had significantly higher mutational burden in genes frequently mutated in ATL than did high-risk, age-matched HTLV-1 carriers who remained ATL-free after a median of 10 years of follow-up. These data show that HTLV-1-infected T-cell clones carrying key oncogenic driver mutations can be detected in cases of ATL years before the onset of symptoms. Early detection of such mutations may enable earlier and more effective intervention to prevent the development of ATL.


Assuntos
Células Clonais/patologia , Evolução Molecular , Infecções por HTLV-I/complicações , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Leucócitos Mononucleares/patologia , Linfócitos T/patologia , Células Clonais/virologia , Humanos , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Leucemia-Linfoma de Células T do Adulto/virologia , Leucócitos Mononucleares/virologia , Estudos Longitudinais , Linfócitos T/virologia , Reino Unido/epidemiologia
16.
J Dermatol Sci ; 97(3): 187-193, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32033869

RESUMO

BACKGROUND: The types of cutaneous lymphoma (CL) and their incidences can vary among geographic areas or ethnic groups. OBJECTIVE: This study aimed to investigate the incidence of various CL types in Japan using epidemiological data from a nationwide registration system for CL. METHODS: A questionnaire was sent to participating hospitals, all of which had been approved to conduct residency programs for board-certified dermatologists by the Japanese Dermatological Association. Data from patients newly diagnosed with CL were collected electronically. RESULTS: Between 2012 and 2017, 2547 new patients with CL from the dermatological institutes were registered. In total, 2090 patients had primary CL and 453 had secondary CL. Those with primary CL included 1609 (77.0 %) patients with mature T- and natural killer (NK)-cell neoplasms, 442 (21.1 %) with B-cell neoplasms, and 39 (1.9 %) with blastic plasmacytoid dendritic cell neoplasms. Mycosis fungoides (MF) was the most common CL subtype in the present study (1003 patients, 48.0 %), and 72.4 % of MF patients had early-stage disease, similar to observations in previous studies on other cohorts. Primary cutaneous CD30+ T-cell lymphoproliferative disorders and adult T-cell leukemia/lymphoma were the second and third most common subtypes, respectively. CONCLUSION: Compared to that in our previous cohort (2007-2011), the number of registered T- and NK-cell CL cases decreased, whereas that of B-cell CL cases increased from 44.8-73.7 patients/year. These results provide insight into CL trends within the Japanese population, which might contribute to a better understanding of the disease.


Assuntos
Leucemia-Linfoma de Células T do Adulto/epidemiologia , Linfoma de Células B/epidemiologia , Linfoma Anaplásico Cutâneo Primário de Células Grandes/epidemiologia , Micose Fungoide/epidemiologia , Neoplasias Cutâneas/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Japão/epidemiologia , Células Matadoras Naturais/patologia , Leucemia-Linfoma de Células T do Adulto/patologia , Linfoma Anaplásico Cutâneo Primário de Células Grandes/patologia , Masculino , Pessoa de Meia-Idade , Micose Fungoide/patologia , Estadiamento de Neoplasias , Sistema de Registros/estatística & dados numéricos , Neoplasias Cutâneas/patologia , Adulto Jovem
17.
Int J Hematol ; 111(2): 234-240, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31721034

RESUMO

Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell neoplasm associated with the human T-cell leukemia virus type-I (HTLV-1); prognosis still remains very poor. We retrospectively reviewed the treatment of 198 patients with acute-, lymphoma- and unfavorable chronic-type ATL (aggressive ATL) diagnosed from 2005 to 2014 in a hospital located in an area of Japan in which HTLV-1 is highly endemic. One-hundred forty-three, and 35 patients were treated using OPEC/MPEC and VCAP-AMP-VECP, respectively. OPEC/MPEC was mainly used until around 2010, and gradually switched to VCAP-AMP-VECP, especially for younger patients. The 2-year overall survival for patients treated by VCAP-AMP-VECP was significantly higher than that using OPEC/MPEC for patients < 70 years old (y.o.), but not for patients ≥ 70 y.o. A less intensive chemotherapy OPEC/MPEC could be performed without reducing dose intensity, even in elderly patients, and its therapeutic outcome is not inferior to that of VCAP-AMP-VECP. It is difficult to draw definite conclusion from this small retrospective study; however, OPEC/MPEC may represent an alternative option for elderly patients with aggressive ATL.


Assuntos
Infecções por Deltaretrovirus/epidemiologia , Leucemia-Linfoma de Células T do Adulto/terapia , Progressão da Doença , Hospitais/estatística & dados numéricos , Vírus Linfotrópico T Tipo 1 Humano , Humanos , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Estudos Retrospectivos
18.
Cancer ; 126(3): 567-574, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31769871

RESUMO

BACKGROUND: Globally, 5 million to 10 million people are infected with human T-cell leukemia virus type 1, which causes adult T-cell leukemia/lymphoma (ATLL) in 2% to 5% of the carriers. ATLL is a rare but extremely aggressive malignancy that can be challenging to diagnose. Very little data exist on the incidence patterns of ATLL in the United States. METHODS: ATLL cases reported to the National Program of Cancer Registries, the Surveillance, Epidemiology, and End Results (SEER) program, and the New York State Cancer Registry were used for the study. Age-adjusted incidence rates were calculated by age, race/ethnicity, sex, and year of diagnosis. The 5-year survival rate was compared among race/ethnicity groups with the SEER data. RESULTS: During 2001-2015, 2148 ATLL cases were diagnosed in the United States, 18% of which were in New York State. New York State had the highest incidence rate for ATLL, with a rising trend especially among non-Hispanic blacks (NHBs), whereas the incidence was stable across the remainder of the United States. NHBs were diagnosed at a younger median age (54 years) and had a shorter overall survival (6 months). In New York City, only 22.6% of the ATLL cases diagnosed were born in North America. CONCLUSIONS: This is the largest epidemiological study of ATLL in the United States and shows a rising incidence in New York City. NHBs have a younger age at presentation and poor overall survival. The rising incidence is largely due to NHBs originating from the Caribbean.


Assuntos
Leucemia-Linfoma de Células T do Adulto/epidemiologia , Linfoma/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Leucemia-Linfoma de Células T do Adulto/patologia , Leucemia-Linfoma de Células T do Adulto/terapia , Linfoma/patologia , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , América do Norte/epidemiologia , Programa de SEER , Estados Unidos/epidemiologia , População Branca , Adulto Jovem
20.
PLoS One ; 14(5): e0217560, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31136642

RESUMO

Human T-cell lymphotropic virus (HTLV) belongs to a larger group of primate T-cell lymphotropic viruses (PTLVs) within the family Retroviridae. It is estimated that 10 to 20 million people worldwide may be infected with HTLV-1. Although most of them are asymptomatic, around 5% of infected individuals may develop either HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) or Adult T-cell Leukaemia/Lymphoma (ATLL). Public Health authorities in many countries have implemented routine blood-donor tests for HTLV-specific antibodies; but this is not the case for Germany since the reported prevalence is very low (7/100,000). With the aim to evaluate retrospectively the presence of HTLV-1 among oncology patients in this country, samples stored at the Universitätsklinikum Freiburg, were analyzed. For this purpose, two different nested-PCR (n-PCR) protocols have been modified and set up for HTLV-1 detection. One positive case was detected by n-PCR among 406 samples (0,25%) in a period of 5 years (2008-2012) corresponding to a T-Cell Lymphoma. Despite the low prevalence, this virus is circulating in Germany, probably due to the increasing numbers of immigrants in these last years. Physicians should consider HTLV-1 infection and suspect it taking in account the ethnic and relation to endemic regions regardless the patient's residence.


Assuntos
Doadores de Sangue , Vírus Linfotrópico T Tipo 1 Humano/genética , Leucemia-Linfoma de Células T do Adulto/genética , Paraparesia Espástica Tropical/genética , Reação em Cadeia da Polimerase , Adulto , Feminino , Alemanha , Humanos , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Masculino , Pessoa de Meia-Idade , Paraparesia Espástica Tropical/epidemiologia , Estudos Retrospectivos
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