Incidence Of Adult T-cell Leukemia/lymphoma Research Articles

A decrease in newly diagnosed patients with adult T-cell leukemia/lymphoma in Kagoshima, a highly endemic area of HTLV-1 in southwestern Japan

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.

Effect of HTLV-1 Infection on the Clinical Course of Patients with Rheumatoid Arthritis

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.

Mortality and risk of progression to adult T cell leukemia/lymphoma in HTLV-1–associated myelopathy/tropical spastic paraparesis

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.

HTLV-1 Infection and Rheumatic Diseases.

Some major research and clinical questions about human T-cell leukemia virus type 1 (HTLV-1) infection and rheumatic diseases remain: (1) Does HTLV-1 infection cause rheumatic diseases? (2) Do patients with rheumatic diseases display different responses to treatment with anti-rheumatic agents when they are HTLV-1 carriers? (3) Is adult T-cell leukemia/lymphoma (ATL) or HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) more prevalent in HTLV-1 carriers with rheumatic diseases who are treated with anti-rheumatic agents? These questions are important because increasing numbers of patients with rheumatic diseases are currently receiving treatment with aggressive medicines such as immunosuppressants and biologics. Studies on HTLV-1 gene-transgenic mice have shown manifestations resembling rheumatic diseases. Epidemiological studies have shown a high incidence of HTLV-1 infection in patients with rheumatic diseases including rheumatoid arthritis (RA), Sjogren’s syndrome, and polymyositis. HTLV-1-positive and HTLV-1-negative patients with RA have displayed similar immunological features including the seroprevalence of anti-citrullinated peptide antibodies. Conversely, attenuated effectiveness of tumor necrosis factor inhibitors for HTLV-1-positive patients with RA in Japan has been reported. Therefore, although no direct evidence has shown that HTLV-1 infection alone causes rheumatic diseases, HTLV-1 may affect the inflammation of RA. Although the incidence of ATL or HAM/TSP among patients with rheumatic diseases has not been investigated in large-scale studies, ATL or HAM/TSP has developed among HTLV-1-positive patients with rheumatic diseases. HTLV-1 infection may affect the clinical course of patients with rheumatic diseases, particularly after receiving anti-rheumatic agents. Because studies on these issues are limited, further investigation with large sample sizes is necessary.

Incidence of adult T-cell leukemia/lymphoma in nonendemic areas.

Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell neoplasm with extremely poor prognosis caused by human T-cell leukemia virus type 1 (HTLV-1). The distribution of HTLV-1 and the incidence of ATLL in endemic areas have been well described, however, little is known about the incidences and the trends of the disease in nonendemic areas. Recently, studies have shown that the HTLV-1 carriers are increasing in nonendemic areas. Also, the incidence of ATLL seems to be significantly increasing in nonendemic areas suggesting that HTLV-1 carriers have emigrated from endemic areas. These epidemiologic studies indicate the necessity of edification of the disease caused by HTLV-1 and establishing appropriate preventive methods against infection in nonendemic areas.

The incidence of adult T-cell leukemia/lymphoma among human T-lymphotropic virus type 1 carriers in Japan

Human T-lymphotropic virus type 1 (HTLV-1) is highly endemic in the Kyushu/Okinawa region of Japan. A nationwide investigation verified the frequency of HTLV-1 carriers among first-time blood donors and the occurrence of newly diagnosed adult T-cell leukemia/lymphoma (ATL) cases from 2007 through 2008. After adjusting for differences in capture rate between areas, the age-, sex- and area-specific incidence of ATL among carriers was determined. Annual ATL incidence among 10 000 carriers was 7.7 and 8.7 for the Kyushu and non-Kyushu/Okinawa regions, respectively. The incidence increased sharply for men from their 40s to their 70s, but the rate in females remained unchanged through their 40s to 70s. ATL incidence in middle-aged females was still low, even if female carrier frequency was assumed to be identical to that of males. Patients with ATL in their 60s and 70s will comprise two-thirds of all patients with ATL for the next 15 years in Japan.

Time Trend and Age-Period-Cohort Effects on the Incidence of Patients with Adult T-Cell Leukemia in a Population-Based Study in Japan, 1991-2010

Background: Adult T-cell leukemia-lymphoma (ATL) is an aggressive T-cell malignancy, which is exclusively associated with human T-cell leukemia virus type I (HTLV-1) infection. Japan is a well-known endemic area of ATL, with approximately 400 new cases and 1,000 deaths annually. A recent Japanese study reported that the trend in the age-standardized incidence rate of ATL has remained relatively stable. However, age-standardized rate may mask important epidemiological characteristics related with age and birth-cohort. To date, several epidemiological studies reported the interesting birth-cohort patterns on the incidence of lymphoid malignancies. However, little has been known about the effects of age and birth-cohort on the time trend in the incidence of ATL.Methods: A dataset of patients with ATL (ICD-O-3 code 9827) was obtained from the Nagasaki Prefecture Cancer Registry that contains all cancer data from a population of approximately 1.5 million since 1985. To calculate the average annual percent change (AAPC) for crude incidence rate and age-standardized (world) incidence rate (ASRw) (per 100,000), the Joinpoint Regression Program with Hudson’s method was used. The effects of age, calendar-period, and birth-cohort on the time trends of the ATL incidence were evaluated by performing the age-period-cohort (APC) analysis using the R-package Epi. For the APC analysis, ten 5-year age groups and five 5-year calendar periods were set, resulting to create 14 birth cohorts. Parameter estimates of the APC models were obtained by fitting five models (age, age-drift, age-period, age-cohort, and age-period-cohort). In the full model of the age-period-cohort model, period and birth cohort effects were evaluated as relative risk (RR). This work was supported in part by the Health Labour Sciences Research Grant (H26-sinkoujitsuyouka-ippan-013).Results: A total of 1,971 patients (1,085 men and 886 women) who were diagnosed during 1991-2010 were analyzed. The crude incidence rate showed a slightly increasing tendency from 8.2 (year 1991) to 9.7 (year 2010) for men (AAPC, +0.6, 95%CIs, -1.6 to 1.8) and 5.7 (year 1991) to 8.4 (year 2010) for women (AAPC, +1.3, 95%CIs, -0.2 to 2.8), without statistically significant. Meanwhile, the ASRw showed a significantly decreasing tendency from 5.2 (year 1991) to 3.7 (year 2010) for men (AAPC, -2.1, 95%CIs, -3.2 to -1.1) and from 3.5 (year 1991) to 2.5 (year 2010) for women (AAPC, -1.8, 95%CIs, -3.3 to -0.3). The age-specific incidence rate was highest in patients aged 70 years or older, particularly the rate in patients aged 80 years or older drastically increased after year 2003. In the APC analyses, both the age-cohort model and age-period model were statistically significant for men (P<0.0001 for both) and women (P=0.002 for both), indicating that both a cohort effect and a period effect were the major effects on the incidence of ATL. The RR among various cohorts showed a drastic difference of the cohort effect on the ATL incidence from a higher risk in cohorts before 1931 but a lower risk in cohorts after 1931 in men, and from a higher risk in cohorts before 1940 but a lower risk in cohorts after 1940 in women. The RR among various periods was almost stable in 1, but becomes high after the period 2000 in both sexes.Discussion and Conclusion: The earlier birth-cohort and the recent calendar period were significantly associated with the incidence of ATL beyond the age effect. The birth cohort effect reflects the exposure to environmental factors, thus the effect can be explained by the higher HTLV-1 infection in early generation. Sex difference in the cohort effect may be reflected the way of life, biological, and behavioral factors. Continued ATL incidence and careful analysis of period effects are of importance to elucidate this unique epidemiology of ATL. DisclosuresNo relevant conflicts of interest to declare.

Soluble CD30 and peripheral blood or pulmonary involvement of adult T-cell leukemia/lymphoma

Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive leukemia/lymphoma which was discovered in Japan [1,2]. The long clinical latency and low incidence of ATL indicate that ATL is an agerelated disease and some genetic changes are involved in malignant transformation and monoclonal expansion of the human T-cell leukemia virus type 1 (HTLV-1)-infected cells [3]. HTLV-1-mediated T-cell transformation presumably arises from a multistep oncogenic process in which the virus induces chronic T-cell proliferation with accumulation of genetic defects followed by dysregulation of cell growth [4]. Monoclonal proliferation of HTLV-1-infected cells is observed in upwards of 5% of patients who ultimately develop ATL, constituting the high risk group for ATL development [5]. We previously reported that HTLV-1-infected cells and ATL cells exhibit CD30 and soluble CD30 (sCD30) is elevated in the sera of patients with ATL [6]. CD30, a 120 kDa type I cell surface glycoprotein, is a member of the tumor necrosis factor receptor superfamily [7]. CD30 expression is dependent on mitogen or viral activation and proliferation of B and T cells. CD30+ cells release sCD30 in vitro and in vivo [8], detected at low levels in the sera of healthy donors [9].The question remains as to where the ATL cells proliferate and produce sCD30? We have focused on the monoclonal proliferation of T cells and chronic inflammation in the microenvironment in vivo.

Malignant diseases and mortality in blood donors infected with human T-lymphotropic virus type 1 in Israel

The natural history of blood donors infected with human T-lymphotropic virus type 1 (HTLV-1) in Israel has never been assessed. The aim of this study was to evaluate the prevalence of malignant disorders and mortality among a cohort of Israelis diagnosed as HTLV-1 carriers during routine blood unit screening. This was an observational retrospective cohort study. All HTLV-1 cases among Israeli blood donors between 1995 and 2009 were included. Data regarding malignant diseases were extracted from the Israel National Cancer Registry. Mortality data were extracted from the Israel Population Registry. Between January 9, 1995 and December 31, 2009, 1574497 blood donors were screened for HTLV-1 in the central blood bank services. Of these, 90 were found to be HTLV-1 carriers. This cohort of HTLV-1-infected blood donors was followed for an average of 9.2 ± 6 years. Among them six (6.7%) were diagnosed as having malignant diseases, four of them with adult T-cell leukemia/lymphoma (ATLL). The incidence of ATLL was 0.37 (95% confidence interval 0.13-1.08)/100 HTLV-1 carrier-years. We found a high rate of malignant diseases among HTLV-1-infected blood donors.

Trends of incidence rate of adult T‐cell leukemia/lymphoma in an HTLV‐1 endemic area in Japan

Trends of incidence rate of adult T‐cell leukemia/lymphoma in an HTLV‐1 endemic area in Japan

Methylenetetrahydrofolate reductase genotype does not play a role in adult T-cell leukemia/lymphoma pathogenesis among human T-lymphotrophic virus type 1 carriers

Human T-lymphotropic virus type 1 (HTLV-1) is associated with adult T-cell leukemia/lymphoma (ATL). However, the incidence of ATL is low among HTLV-1 carriers suggesting additional mechanisms are involved in the progression of the disease. A recent study found that polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene influence the susceptibility to malignant lymphoma. We have analyzed the MTHFR genotype in 81 HTLV-1 carriers and 87 ATL patients. No statistically significant associations were found between MTHFR genotype and development of ATL. These data suggest that genetic polymorphisms in the MTHFR locus do not play a role in ATL pathogenesis among HTLV-1 carriers.

Cutaneous lymphomas in Tokyo: analysis of 62 cases in a dermatology clinic.

The epidemiology of cutaneous lymphomas revealed that the incidence of lymphomas differed depending on various factors including area, race, and sex, among others. This study was undertaken to analyse the incidence of cutaneous lymphomas in Tokyo. The clinical records and histologic material from 50 patients with lymphomas of the skin and 12 patients with lymphomatoid papulosis seen during the last 10 years at the Department of Dermatology, The Jikei University School of Medicine, Tokyo, have been reviewed. T-cell lymphomas including mycosis fungoides (MF)-Sézary's syndrome (SS) complex and adult T-cell leukemia/lymphoma (ATL) were more frequent than B-cell lymphomas. The incidence of ATL is associated with the number of human T-cell lymphotropic virus type 1 (HTLV-1) carriers in the general population. Cutaneous B-cell lymphoma (CBCL) is not as rare as previously thought in Japan. Although the frequency of these cases depends on many unrelated factors, these values can provide a rough indication of the incidence of cutaneous lymphomas in Tokyo. The incidence of cutaneous lymphomas may be influenced by changes in environmental factors including viral infections.

The world health organization classification of malignant lymphomas in japan: incidence of recently recognized entities. Lymphoma Study Group of Japanese Pathologists.

New insights into the immunology and genetics of malignant lymphomas have allowed the recognition of new entities and the refinement of previously recognized disease categories. The relative incidence of these subtypes of malignant lymphoma is also known to differ according to geographic location. In order to clarify the current status of malignant lymphomas in Japan and the relative incidences of their subtypes, 3194 patients were classified according to the new World Health Organization (WHO) classification. Among these were 3025 cases (94.71%) of non-Hodgkin's lymphoma (2189 cases (68.53%) of B-cell lymphoma, 796 cases (24.92%) of T-cell lymphoma) and 141 cases (4.41%) of Hodgkin's lymphoma. The incidences of the major subtypes of non-Hodgkin's lymphoma were 33.34% for diffuse large B-cell lymphoma, 8.45% for marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type, 8.05% for plasma cell myeloma, 7.45% for adult T-cell leukemia/lymphoma (ATLL), 6.7% for follicular lymphoma, 6.67% for peripheral T-cell lymphoma of unspecified type, 2.79% for mantle cell lymphoma, 2.6% for nasal and nasal-type T/NK cell lymphoma, 2.35% for angioimmunoblastic T-cell lymphoma, and 2.35% for precursor B-cell lymphoblastic leukemia/lymphoma, in decreasing order. The other subtypes comprised less than 2%, mainly precursor T-cell lymphoblastic lymphoma/leukemia (1.72%), anaplastic large-cell lymphoma of T- and null-cell types (1.53%), and B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (1.31%). The incidence of ATLL was influenced by its high percentage (19.20%) in the south-western Japanese island, Kyushu, an endemic area of human T-cell leukemia virus type 1 (HTLV-1), but which appeared to be lower than that in a previous study. The nodular sclerosis and mixed cellularity types of Hodgkin's disease occupied 1.78% and 1.63%, respectively. These data are distinct from those in Western countries and similar in several ways to those in the East, although the relatively high rate of ATLL was attributed to the geographical difference in the etiologic factor, HTLV-1.

Evaluation of adult T-cell leukemia/lymphoma incidence and its impact on non-Hodgkin lymphoma incidence in southwestern Japan.

The incidence of adult T-cell leukemia/lymphoma (ATL) and its impact on that of total non-Hodgkin lymphoma (NHL) were evaluated in Nagasaki, an area in southwestern Japan where human T-cell lymphotropic virus type I (HTLV-I) is endemic. The first study area comprised 4 towns located on the K Islands, which had a population of 26,870 in 1990. The overall HTLV-I seroprevalence estimated from the serologic survey of 18,485 subjects was 16.2%. By using the data from the Nagasaki Prefectural Cancer Registry (NPCR) and reviewing clinical and laboratory information, we identified 40 cases of ATL and 35 cases of other NHL diagnosed between 1985 and 1995. The crude annual incidence of ATL among 100,000 HTLV-I carriers aged 30 or older was estimated at 137.7 for men and 57.4 for women, with a significant sex difference after adjustment for age (rate ratio = 2.50, 95% confidence interval 1.32-4.73). The cumulative risk from 30 to 79 years of age was estimated at approximately 6.6% for men and 2.1% for women. Among the entire population, ATL accounted for 51 to 59% of the total NHL incidence, showing the strong impact of HTLV-I infection. The second study area comprised the whole of Nagasaki Prefecture (total population in 1990 = 1.56 million). Between 1985 and 1995, 989 cases of ATL and 1,745 cases of other NHL were registered in the NPCR. The world age-standardized annual incidence rate of ATL per 100,000 persons aged 30 or older was estimated at 10.5 for men and 6.0 for women, which accounted for approximately 37 to 41% of the total NHL incidence.

ＨＴＬＶ‐１感染からＡＴＬ発症まで 成人Ｔ細胞白血病・リンパ腫におけるＨＴＬＶ‐１変異と組み込み部位の変化の意義

Human T-lymphotropic virus type 1 (HTLV-1) is etiologically associated with adult T-cell leukemia/lymphoma (ATL), and the diverse clinical features of this disease have led to its subclassification. The incidence of ATL is rather low among HTLV-1 carriers, and those who develop the disease usually have a 40-to 60-year latency period from the time of infection to proggression to ATL. The tumor suppressor genes such as p53, p15 and p16, are abnormal in aggrassive ATL. Sometimes, the abnormalities appear at the time of crisis. However, the precious mechanism of multi-step leukemogenesis in ATL remains unknown.In all types of ATL, the monoclonal integration of the HTLV-1 provirus into tumor cells can be detected by Southern blotting. The integration patterns of the provirus have clinical implications for ATL. The multiple, complete and defective types in that order are apparently associated with prognosis from good to bad. Sequential Southern blotting for the HTLV-1 and T-cell receptor beta genes disclosed frequent clonal change at crisis from indolent ATL. This change is a peculiar phenomenon, in contrast to the clonal evolution characteristic of the multistep carcinogenesis of most human malignancies, probably reflecting the emergence of multiple premalignant clones in viral leukemogenesis as suggested in Epstein-Barr virus associated lymphomagenesis in the immunocompromised host.

HTLV-I infection and adult T-cell leukemia in Brazil: an overview.

Human T-cell lymphotropic Virus Type I (HTLV-I) is the etiologic factor for adult T-cell leukemia/lymphoma (ATL). HTLV-I infection can also lead to other diseases, such as HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), uveitis, arthropathy and infectious dermatitis. Studies of the infectious mode of transmission of HTLV-I and risk factors for HTLV-I-related diseases have been conducted in several countries, and differences in the prevalence, age patterns, ethnic groups and clinical presentation of the related diseases have been described worldwide. Based on the geographical characteristics of Brazil and data from the literature, we have summarized the distribution of seroprevalence in blood donors in different states around the country, as well as the incidence of ATL in regards to the endemic foci. ATL in Brazil has the same characteristics as those described elsewhere, but is reported more frequently at a younger age. In order to better evaluate ATL in Brazil, a registry has been established at the several hematologic centers under the sponsorship of the instituto Nacional de Cancer and the Brazilian Society of Hematology and Hemotherapy, for the purpose of recording all cases originally diagnosed in Brazil.

Prevention of Mother-to-Child Transmission of Human T-Lymphotropic Virus Type-I

Human T-cell lymphotropic virus type I (HTLV-I), an etiologic human retrovirus of adult T-cell leukemia/lymphoma (ATLL), causes approximately 60 new cases of ATLL each year in Nagasaki Prefecture; essentially all cases are fatal, and they account for approximately 0.5% of total deaths in the area. The estimated life risk for an HTLV-I carrier to develop ATLL is approximately 5%. The major transmission pathway of HTLV-I peculiarly endemic in the Nagasaki Prefecture was studied. The prevalence of HTLV-I infection in children of carrier mothers (21%) was significantly higher than that in children in the general population in the area (1%) and more than 85% of mothers of carrier children were carriers. The breast milk of carrier mothers contained HTLV-I-infected cells and was infectious for marmoset via oral administration. A retrospective survey of children of carrier mothers showed that the prevalence of carrier children of carrier mothers was 17 (39%) of 44 and 0 (0%) of 10 when they were given breast milk only or formula only, respectively. These data provide a powerful basis for devising an intervention measure to block the endemic cycle of HTLV-I, ie, if carrier mothers refrain from breast-feeding, the incidence of ATLL will be significantly reduced some 50 years later.

The 4th nation‐wide study of adult T‐cell leukemia/lymphoma (ATL) in Japan: Estimates of risk of ATL and its geographical and clinical features

To estimate the annual incidence of adult T-cell leukemia/lymphoma (ATL) by district in Japan, a large-scale nationwide survey of ATL and of non-Hodgkin's lymphoma was performed in 1988. Questionnaires for the registration of ATL and of T-cell and non-T-cell lymphoma were distributed to the physicians in charge of this survey in 1,287 hospitals with 200 or more beds throughout Japan. From the positive rate of anti-HTLV-I antibody in adults, the annual incidence of ATL was estimated at 697, independently of the present survey. In fact, 657 cases (47% of the estimated number), newly diagnosed during the 2 years January 1986 to December 1987, were registered from 191 general hospitals throughout Japan. Major results obtained from the present survey are as follows: (1) among all ATL cases registered, 51% were from Kyushu and 29% were from metropolitan areas (Kanto, Chubu and Kinki) and most, but not all, patients with ATL in the metropolitan areas had come from the ATL-endemic areas and settled in the metropolitan areas; (2) the estimated annual incidence rates of ATL per million adults were 40.4 in males and 26.4 in females in Kyushu, the overall risk of ATL being 1.5 times as high in males as in females; (3) the age-specific incidence rate in Kyushu increased steeply with age until the age of 70, and then decreased markedly in both sexes; (4) the ratio of T-cell versus non-T-cell lymphomas was 2.9 in Kyushu but 0.5 in other districts of Japan, however, this difference regressed to the average for the whole of Japan if ATL cases were excluded; (5) 26.5% of patients with ATL had a family history of cancer, and among these, 14 (8.2%) were ATL, 21 (12.2%) were lymphoma and 17 (9.9%) were hematopoietic malignancies, the incidence of which was markedly higher than in the general population; (6) with regard to clinicopathological features of ATL, there were more advanced cases in south Kyushu than in other districts, however, these differences were not statistically significant. To clarify the chronological changes and geographical variations in the annual incidence of ATL in Japan, continuous systematic nationwide surveillance is necessary and further nation-wide studies are being prepared.

Modelling the risk of adult T-cell leukemia/lymphoma in persons infected with human T-lymphotropic virus type I.

Adult T-cell leukemia/lymphoma (ATL), a malignancy of mature CD4-positive lymphocytes, has been etiologically linked to the human retrovirus HTLV-I. Although a long latent period is suggested from migrant studies, little prospective information on the risk of developing ATL among persons with HTLV-I infection is available. We present here a model for ATL risk based upon age- and sex-specific HTLV-I seroprevalence data from a cross-sectional survey of 13,000 Jamaicans and ATL incidence data from a 2 1/2-year case-control study. By examining the age-specific incidence of ATL relative to both adult and childhood-acquired seropositivity versus childhood-acquired seropositivity alone, we provide evidence in support of the hypothesis that childhood infection with HTLV-I is important to the development of ATL. Using this model, the cumulative lifetime risk of ATL for those infected before age 20 is estimated to be 4.0% for males and 4.2% for females. Under this hypothesis, HTLV-I-associated diseases with shorter latent periods, such as tropical spastic paraparesis, should have a higher incidence in adult females than in adult males.

Epidemiological features of HTLV-I carriers and incidence of ATL in an ATL-endemic island: a report of the community-based co-operative study in Tsushima, Japan.

To extend the epidemiological study on adult T-cell leukemia-lymphoma (ATL) in Japan, the geographical and demographic characteristics of carriers of human T-lymphotropic virus type I (HTLV-I) and patients with ATL were analyzed in Tsushima Island, which is one of the typical endemic areas of ATL in Kyushu, Japan. Even on the small island of Tsushima (710 km2; pop. 48,875; 123 villages), the positive rates of anti-HTLV-I antibody among the 58 villages studied varied from 2% to 50%, a fact that is probably associated with the historical events affecting the movement of the indigenous population of Tsushima Island. The positive rate of anti-HTLV-I antibody in males increased little with age; however, the female rate increased distinctly with age in moderate and high HTLV-I-endemic villages where more than 15% of the inhabitants had positive anti-HTLV-I antibody. Analysis of anti-HTLV-I antibody positivity between spouses confirmed that HTLV-I was more contagious from husband to wife than from wife to husband, which corresponded to the fact that the positive rate of anti-HTLV-I antibody in females older than 30 years was higher than that in males. Recently the rate of carrier children from HTLV-I carrier mothers was estimated at around 20%. The recent annual incidence rates of ATL among 1,000 HTLV-I carriers older than 40 years living in Tsushima Island was estimated at 2.2 in males, 0.8 in females.