Adult T-Cell Leukemia/Lymphoma and Cluster of HTLV-I Associated Diseases in Brazilian Settings

We studied the transmission routes of human T-cell lymphotropic virus type I (HTLV-I) within families of 82 Brazilian patients diagnosed with adult T-cell leukaemia/lymphoma (ATL). Diagnosis of ATL in 43 male and 39 female patients was based on clinical and laboratory criteria of T-cell malignancy and detection of HTLV-I monoclonal integration. Samples were tested for HTLV antibodies and infection was confirmed as HTLV-I by Western Blot and/or polymerase chain reaction (PCR) assays. Overall 26/37 (70%) of mothers, 24/37 (65%) of wives, 8/22 (36%) of husbands, 34/112 (30%) of siblings and 10/82 (12%) offspring were HTLV-I infected. In 11 ATL patients, mothers were repeatedly HTLV-I seronegative, but HTLV-I pol or tax sequences were detected in 2 out of 6 cases tested by PCR. ATL patients with seronegative mothers related the following risk factors for HTLV-I infection: 6 were breast-fed by surrogate mothers with unknown HTLV-I status, 4 had a sexually promiscuous behaviour and 1 had multiple blood transfusions at a young age. Familial aggregation of ATL and other HTLV-I associated diseases such as HTLV-I myelopathy (HAM/TSP) and or uveitis, ATL in sibling pairs or in multiple generations was seen in 9 families. There were 6 families with ATL and TSP sibling pairs. In 3 families at least one parent had died with lymphoma or presenting neurological diseases and 2 offspring with ATL. Further to the extent of vertical and horizontal transmission of HTLV-I infection within ATL families, our results demonstrate that mothers who provide surrogate breast-milk appear to be an important source of HTLV-I transmission and ATL development in Brazil.     

Risk of human T-lymphotropic virus type I-associated diseases in Jamaica with common HLA types

Human T-lymphotropic virus-I (HTLV-I) causes adult T-cell leukemia/lymphoma (ATL) and HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP). We postulated a higher disease risk for people with common human leukocyte antigen (HLA) types, due to a narrower immune response against viral or neoplastic antigens, compared to people with uncommon types. HLA class-I (A,B) and class-II (DRB1, DQB1) allele and haplotype frequencies in 56 ATL patients, 59 HAM/TSP patients and 190 population-based, asymptomatic HTLV-I-infected carriers were compared by logistic regression overall (score test) and with odds ratios (ORs) for common types (prevalence >50% of asymptomatic carriers) and by prevalence quartile. HTLV-I proviral load between asymptomatic carriers with common versus uncommon types was compared by t-test. ATL differed from asymptomatic carriers in overall DQB1 allele and class-I haplotype frequencies (p 相似文献   

Survey of Anti-human T-Cell Leukemia Virus Type I Antibody in Family Members of Patients with Adult T-Cell Leukemia

To evaluate the intrafamilial clustering of HTLV-I, we examined the sera or plasma of 296 healthy family members of patients with adult T-cell leukemia (ATL) for anti-HTLV-I antibodies. Of 296 subjects, 132 (44.6%) had anti-HTLV-I antibodies. Fifty-nine (41.0%) out of 144 males and 73 (48.0%) out of 152 females were seropositive. The positive rates of antibody to HTLV-I increased with age, especially between the 30–39 and the 40–49 age groups. Five out of 6 fathers, 3 out of 4 mothers, 31 (60.8%) out of 51 spouses, 40 (63.5%) out of 63 siblings and 46 (33.8%) out of 136 children of patients with ATL had anti-HTLV-I antibodies. Of 74 children with an ATL father, 14 (18.9%) were seropositive, while 32 (51.6%) out ot 63 children with an ATL mother were seropositive. This difference was statistically significant ( P <0.001). Of those children with an ATL father, 12 (26.1%) out of 46 whose mothers were HTLV-I carriers had antibodies to HTLV-I. In contrast, none of the 13 children whose mothers were not carriers were seropositive. These results supported the hypothesis that the mother-to-child transmission is one of the most important modes of HTLV-I transmission. In wives of male patients with ATL, the positive rate of antibody to HTLV-I was 65.6% (21/32), and in husbands of female patients, it was 52.6% (10/19). The high positive rate of antibody to HTLV-I not only in wives of male patients but also in husbands of female patients suggests that either HTLV-I is more frequently transmitted from wives to their husbands than we had originally expected, or that ATL may develop even in wives who acquire HTLV-I from their husbands after marriage.     

Survey of anti-human T-cell leukemia virus type I antibody in family members of patients with adult T-cell leukemia

To evaluate the intrafamilial clustering of HTLV-I, we examined the sera or plasma of 296 healthy family members of patients with adult T-cell leukemia (ATL) for anti-HTLV-I antibodies. Of 296 subjects, 132 (44.6%) had anti-HTLV-I antibodies. Fifty-nine (41.0%) out of 144 males and 73 (48.0%) out of 152 females were seropositive. The positive rates of antibody to HTLV-I increased with age, especially between the 30-39 and the 40-49 age groups. Five out of 6 fathers, 3 out of 4 mothers, 31 (60.8%) out of 51 spouses, 40 (63.5%) out of 63 siblings and 46 (33.8%) out of 136 children of patients with ATL had anti-HTLV-I antibodies. Of 74 children with an ATL father, 14 (18.9%) were seropositive, while 32 (51.6%) out of 63 children with an ATL mother were seropositive. This difference was statistically significant (P less than 0.001). Of those children with an ATL father, 12 (26.1%) out of 46 whose mothers were HTLV-I carriers had antibodies to HTLV-I. In contrast, none of the 13 children whose mothers were not carriers were seropositive. These results supported the hypothesis that the mother-to-child transmission is one of the most important modes of HTLV-I transmission. In wives of male patients with ATL, the positive rate of antibody to HTLV-I was 65.6% (21/32), and in husbands of female patients, it was 52.6% (10/19). The high positive rate of antibody to HTLV-I not only in wives of male patients but also in husbands of female patients suggests that either HTLV-I is more frequently transmitted from wives to their husbands than we had originally expected, or that ATL may develop even in wives who acquire HTLV-I from their husbands after marriage.     

Serological survey of antibodies to the adult T-cell leukemia virus-associated antigen (HTLV-A) in Taiwan

A serological survey of antibodies to the adult T-cell leukemia virus-associated antigen (HTLV-A) conducted in Taiwan revealed II seropositive individuals among 2,565 serum donors tested, which included 1,187 hospital or free clinic patients, 1,065 blood donors and 313 aborigines. The overall prevalence rate was 0.43% and was 0.90% (9/995) for adults aged 40 years or over, which was similar to the rates observed in the non-endemic areas in Japan. No highly prevalent area was demonstrated. The II seropositive individuals identified were 8 hospital or clinic patients, 1 blood donor and 2 aborigines. Among 108 various leukemia/lymphoma patients also studied, 7 were positive. These 7 anti-HTLV-A-positive patients also had clinicopathologic features of adult T-cell leukemia/lymphoma (ATL). Among 21 relatives of 3 seropositive individuals in the epidemiologic study, 2 were positive; and among 25 relatives of 5 ATL patients, 6 were positive. Our data support the contention that horizontal familial transmission of human T-cell leukemia virus (HTLV-I) is an important route and HTLV-I infection can occur on a different genetic background. Furthermore, the antibody titer did not correlate with the manifestation or the state of the disease.     

Malignant lymphomas in Japan: Epidemiological analysis of adult T-cell leukemia/lymphoma (ATL)

The incidence of malignant lymphomas in Japan is relatively low compared to that in western European countries and the United States. However, in limited areas in Japan a specific type of lymphoid malignancy called adult T-cell leukemia/lymphoma (ATL), which is caused by human T-cell leukemia virus type I (HTLV-I), is highly prevalent, and there are also many healthy carriers of HTLV-I in the same areas. A cross-sectional seroepidemiological study of HTLV-I showed that the age-specific proportion of healthy HTLV-I carriers in these ATL-endemic areas increased with age, especially over 40, and was higher in females than in males. Three main routes of HTLV-I transmission are recognized: 1) vertical transmission from mother to child mainly through breast milk; 2) horizontal transmission from man to woman through semen, and; 3) parenteral transmission from carrier donor to non-carrier recipient. The annual incidence rate of ATL among HTLV-I carriers is estimated at 2.0 in males and 0.5 in females, and the cumulative risk for ATL in HTLV-I carriers during a 70-year life span is 1%–5%. Possible risk factors for ATL in addition to HTLV-I infection were considered, i.e. genetic factors, environmental factors, nutritional condition, thymus involution etc., but none of these were found to be clearly associated with ATL. To determine whether there exist particularly susceptible hosts for ATL in the ATL endemic areas, HLA types were examined, but no conclusive results on the positive relationships between HLA types and ATL manifestation or HTLV-I infection were obtained. From follow-up studies on the age-specific distribution of HTLV-I carriers in Japan, it is now speculated that the HTLV-I infection rate might have decreased naturally in the more recent generational cohort groups, even in the ATL-endemic areas. However, ATL in Japan is an important subject for study in the field of cancer epidemiology, and several trial intervention programs for the prevention of ATL, such as controls of vertical transmission from mother to child through breast milk, are now ongoing in the ATL-endemic areas of Japan.     

Antibody reactivities to tumor-suppressor protein p53 and HTLV-I Tof,Rex and Tax in HTLV-I-infected people with differing clinical status

Since the presence of anti-p53 antibody has been correlated with the mutation and accumulation of p53, the aim of this study was to detect anti-p53 antibody and understand its correlations with anti-T of, -Rex, or -Tax antibody reactivity in HTLV-I infected people differing in their clinical status. A plasmid (pGEX-Tof) was constructed to express Tof recombinant protein (RP) in Escherichia coli. Serum samples from 50 asymptomatic carriers (ACs), 50 adult T-cell leukemia (ATL) and 50 HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients were assayed for reactivity with different RPs by Western immunoblotting. The results showed that 2% of ACs, 4% of ATL patients and 6% of HAM/TSP patients had anti-p53 antibody. Therefore, anti-p53 antibody is not a useful serological marker for clinical management of HTLV-I infected people. Only I HAM/TSP patient had anti-Tof antibody whose specificity was further confirmed by antibody competition enzyme immunoassay. This study demonstrated that Tof protein is immunogenic in vivo, suggesting that it plays a role in the life cycle and pathogenesis of HTLV-I. The rate of anti-Rex antibody among HAM/TSP patients was significantly higher than that of ACs or ATL patients. In addition, 50% of ACs, 42% of ATL and 98% of HAM/TSP patients had anti-Tax antibody. McNemar's test showed that the presence of anti-p53 antibody did not have any correlation with the anti-Tax antibody in HTLV-I-infected people, while the correlation between anti-p53 and anti-Rex antibodies or anti-p53 and anti-Tof antibodies cannot be ruled out in this study. Int. J Cancer 71:196–202, 1997. © 1997 Wiley-Liss, Inc.     

Familial disposition of adult T-cell leukemia and lymphoma

Sixteen families, each with two or more cases of adult T-cell leukemia or lymphoma were found in the Nagasaki district. Eight of the families had a parent with lymphoma. In the other eight families siblings were involved. Four families with sibling cases are presented in detail. Antibody titres to adult T-cell leukemia associated antigen (ATLA) in cases of ATL, CTL, T-CLL, and pre-ATL cases in Nagasaki were all positive. Of the non-leukemic T-cell malignant lymphoma 62.5 per cent were positive for antibody. The positive rate in healthy spouses and siblings of ATLL patients for ATLA antibody was high (67.5 per cent and 40 per cent respectively). The possibility of ATLV infection through spouses or from mother to child and the meaning of the high familial incidence of ATLL is discussed.     

A study of adult T-cell leukemia/lymphoma incidence in central Brooklyn

Adult T-cell leukemia/lymphoma (ATL), a rare outcome of infection with human T-lymphotropic virus (HTLV-I), is endemic in central Brooklyn, which has a large Caribbean migrant population. Previous studies have suggested that HTLV-I prevalence in central Brooklyn may be similar to that recorded in the Caribbean islands. We established a pilot 1-year surveillance program to identify cases of ATL in 7 of 10 hospitals serving the residents of 18 zip codes of central Brooklyn with a combined population of 1,184,670. Of the 6,198 in-patient beds in the catchment area, approximately 83% were covered. Twelve incident cases of ATL were ascertained, all among persons of Afro-Caribbean descent, indicating an annual incidence in African-Americans in this community of approximately 3.2/100,000 person-years. Unexplained hypercalcemia was the most useful screening method, identifying 3 of 5 patients not referred for possible ATL by a local hematologist. The female:male ratio was 3:1. The age pattern was different from that reported in the Caribbean Basin and closer to the pattern seen in Japan. Our study supports evidence that HTLV-I infection and ATL are endemic in central Brooklyn and suggests that a more intensive surveillance program for this disease coupled with intervention efforts to reduce HTLV-I transmission are warranted.     

HTLV-I Induced Extranodal Lymphomas

HTLV-I induced not only nodal but also primary extranodal lymphomas. In this report we describe 12 patients with HTLV-I induced extranodal T-cell lymphoma collected from the literature and our institute experience. There were 5 males and 7 female patients of middle age positive for HTLV-1 antibody. The sites of primary tumor were gastrointestinal, Waldeyer's ring, skin, facial sinuses, and the pleura. All of these were histologically diffuse lymphomas and most of them were found to be a helper/inducer T-cell phenotype, showing integration of HTLV-I proviral DNA. Late leukemic changes and skin infiltration often occurred, but hypercalcemia was rare. Survival time varied from 4 to 35 months, and late organ infiltrations were common. These HTLV-I induced extranodal lymphomas were compared with HTLV-I unrelated extranodal lymphomas or HTLV-I induced nodal lymphomas (lymphoma type ATL). Between 1981 and 1990, we had 110 ATL patients and of these, 5 (4.6%) were HTLV-I induced primary extranodal lymphomas. The frequency of HTLV-I induced extranodal lymphoma might be much higher than expected because until now attention has not been paid to this entity. From the present review, it is suggested that HTLV-I could cause primary extranodal lymphoma which may have some different characteristics from other types of lymphoma. Therefore, patients with T-cell extranodal lymphomas should be investigated further for the presence of HTLV-I antibody and the tumor cells should be examined for the integration of HTLV-I proviral DNA using Southern blot analysis. However, this is sometimes difficult to detect with small specimens and in these cases the PCR method for detection of HTLV-I proviral DNA is worthwhile doing. It should be stressed that characterization of a monoclonal T-cell tumoral expansion with the integration of HTLV-I proviral DNA can be done by surface marker studies and gene analysis at the primary sites in patients with T-cell lymphoma and HTLV-I antibody. Further collection of cases with HTLV-I induced primary extranodal lymphoma is necessary in order to elucidate the clinical characteristics of this rare variant of ATL more precisely.     

Population differences in immune marker profiles associated with human T-lymphotropic virus type I infection in Japan and Jamaica

The natural history of human T-lymphotropic virus type I (HTLV-I) has been shown to differ markedly by geographic area. The differences include contrasting patterns of risk of adult T-cell lymphoma (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which may be due in part to differences in host immune response to infection. To characterize variations in host immunity across populations, we compared serologic immune marker patterns in HTLV-I-endemic populations in Japan and Jamaica. We matched 204 participants with archived blood from the Miyazaki Cohort Study (Japan) and the Food Handlers Study (Jamaica)-i.e., 51 HTLV-I-positive ("carriers") and 51 HTLV-I-negative individuals ("noncarriers") from each population-by age, sex and blood collection year. We compared plasma concentrations of markers of T-cell-mediated (antigen-specific) and nonspecific immunity using regression models and correlation coefficients. Compared to Jamaican HTLV-I noncarriers, Japanese noncarriers had higher covariate-adjusted mean levels of T-cell activation markers, including antibody to Epstein-Barr virus nuclear antigen-1 (reciprocal titer 27 vs. 71, respectively, p=0.005), soluble interleukin-2 receptor-alpha (477 vs. 623 pg/mL, p=0.0008) and soluble CD30 (34 vs. 46 U/mL, p=0.0001) and lower levels of C-reactive protein (1.1 vs. 0.43 microg/mL, p=0.0004). HTLV-I infection was associated with activated T-cell immunity in Jamaicans but with diminished T-cell immunity in Japanese persons. The observed population differences in background and HTLV-I-related host immunity correspond closely to the divergent natural histories of infection observed among HTLV-I carriers in Japan and Jamaica and corroborate a role for host immune status in the contrasting patterns of ATL and HAM/TSP risk.     

Recent progress in non-Hodgkin's lymphoma study in Japan

Great progress has been made in clinical research on non-Hodgkin's lymphoma during the last 15 years. Surface marker and DNA analyses of immunoglobulin and T-cell receptor genes are essential for new classification of the disease according to the cellular origin of tumor cells. This approach resulted in the establishment of new disease entities such as adult T-cell leukemia/lymphoma(ATL), immunoblastic lymphoadenopathy (IBL)-like T-cell lymphoma, and the pleural B-lymphoma occurring in long-standing pyothorax. New retrovirus, HTLV-I, was found during studies on ATL. Prevention of HTLV-I infection is an important project. HTLV-I negative ATL was also found and is of particular interest in understanding leukemogenesis of ATL. An oncogen such as bcl-2 is important for characterization of follicular lymphoma. Prognostic factors of patients with T-lymphoma are completely different from those of B-lymphoma. Risk grouping by combination of major prognostic factors is useful for the selection of the best treatment modality and the accurate estimation of prognosis of patients at initial presentation. The effect of combination chemotherapy should be evaluated separately between T- and B-lymphomas because of the difference in response rate and prognostic factors.     

Mother-to-child transmission of human T-cell leukemia virus type I (HTLV-I): a fifteen-year follow-up study in Okinawa, Japan

Okinawa prefecture is one of the endemic areas for adult T-cell leukemia/lymphoma (ATLL) in Japan. In this study, 2,013 serum specimens drawn serially over a period of 15 years (1968-1983) from 311 mother/child pairs in Okinawa were tested for antibodies to human T-cell leukemia virus type I (HTLV-I) by enzyme-linked immunosorbent assay and by indirect immunofluorescence. The prevalence rate of HTLV-I antibodies was 20.9% (65 cases) in the mothers and 3.2% (10 cases) in the children. Of the 65 seropositive mothers, 10 (15.4%) had seropositive children. This study revealed a significant difference between the prevalence rates of HTLV-I antibodies in mothers and children. In addition, children born to seropositive mothers had acquired their HTLV-I antibodies by the age of 3 years, and were still seropositive at the age of 18 years. No initially seronegative child was found to have seroconverted during the period investigated.     

HTLV-I induced extranodal lymphomas.

HTLV-I induced not only nodal but also primary extranodal lymphomas. In this report we describe 12 patients with HTLV-I induced extranodal T-cell lymphoma collected from the literature and our institute experience. There were 5 males and 7 female patients of middle age positive for HTLV-I antibody. The sites of primary tumor were gastrointestinal, Waldeyer's ring, skin, facial sinuses, and the pleura. All of these were histologically diffuse lymphomas and most of them were found to be a helper/inducer T-cell phenotype, showing integration of HTLV-I proviral DNA. Late leukemic changes and skin infiltration often occurred, but hypercalcemia was rare. Survival time varied from 4 to 35 months, and late organ infiltrations were common. These HTLV-I induced extranodal lymphomas were compared with HTLV-I unrelated extranodal lymphomas or HTLV-I induced nodal lymphomas (lymphoma type ATL). Between 1981 and 1990, we had 110 ATL patients and of these, 5 (4.6%) were HTLV-I induced primary extranodal lymphomas. The frequency of HTLV-I induced extranodal lymphoma might be much higher than expected because until now attention has not been paid to this entity. From the present review, it is suggested that HTLV-I could cause primary extranodal lymphoma which may have some different characteristics from other types of lymphoma. Therefore, patients with T-cell extranodal lymphomas should be investigated further for the presence of HTLV-I antibody and the tumor cells should be examined for the integration of HTLV-I proviral DNA using Southern blot analysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum deoxythymidine kinase in adult T-cell leukemia-lymphoma and its related disorders

Serum deoxythymidine kinase (TK) was measured in 15 patients with the acute type of adult T-cell leukemia (ATL), in 4 with chronic ATL, in 10 with lymphoma type ATL, in 9 with pre-ATL, in 11 with human T-cell leukemia virus type I (HTLV-I) associated with myelopathy (HAM) and in 19 HTLV-I carriers. All these patients were positive for anti-HTLV antibody. The level of TK in pretreatment serum was highest in acute ATL (15.6-1600 U/l, median 107 U/l). It was elevated in chronic ATL (5.4-55.0 U/l, median 37.6 U/l) and lymphoma ATL (6.8-316 U/l, median 16.8 U/l) but normal in pre-ATL (1.8-4.7 U/l, median 2.8 U/l), HAM (1.2-6.0 U/l, median 3.0 U/l) and HTLV-I carriers (1.1-4.6 U/l, median 2.3 U/l). Statistical examination revealed a significant difference between the levels of acute ATL and chronic ATL/lymphoma ATL. In the patients of this series, a close correlation between the level of TK and lactic dehydrogenase (LDH) was statistically present (p less than 0.01). These facts indicate that TK level is a useful indicator of the aggressiveness of ATL cells.     

Clustering and clinical diversity of adult T-cell leukemia/lymphoma associated with HTLV-I in a remote black population of French Guiana

An epidemiological study was performed in French Guiana (population 115,000) to determine the prevalence and incidence of adult T-cell leukemia/lymphoma (ATL) associated with human T-cell leukemia/lymphoma virus type I (HTLV-I). From January 1990 to December 1993, all suspected cases of ATL were enrolled in this study, and their clinical, epidemiological and immunovirological features were analyzed. Out of the 19 suspected cases, 18 were considered as ATL associated with HTLV-I (8 acute forms, 8 lymphoma types and 2 smoldering cases). Before this study, only 2 ATL cases had been reported in French Guiana over a 10-year period. This demonstrates that the number of ATL cases is greatly underestimated in most tropical HTLV-I endemic areas unless a specific disease search is performed. The mean age of the patients was 41 years. While HTLV-I antibodies were present in all cases, molecular studies demonstrated a clonal integration of HTLV-I in the tumoral cells in 7 cases out of the 9 tested. Fifteen patients died within a year of diagnosis. The crude incidence rate of ATL in French Guiana is around 3.5/100,000/year, a situation similar to that found in the Caribbean and in HTLV-I-endemic regions of Japan. However it reaches around 30/100,000/year (highest incidence ever described) in a small remote ethnic group of African origin (around 6200 inhabitants). Possible causes of ATL clustering in this ethnic group are presented. © 1995 Wiley-Liss, Inc.     

Human T-cell lymphotropic virus type I (HTLV-I) antibodies in pre-diagnostic serum of patients with familial adult T-cell leukemia/lymphoma (ATL)

In a study of 7498 American men of Japanese ancestry in Hawaii, 26 incident cases of leukemia or non-Hodgkin's lymphoma were identified after a follow-up period of 19 years. Two of the cases, who were brothers, were diagnosed with adult T-cell leukemia/lymphoma (ATL). Both of these brothers had human T-cell lymphotropic virus type I (HTLV-I) antibodies in their stored serum which were obtained 4 and 18 years before diagnosis. None of the 24 patients with other hematologic malignancies or the 26 matched controls were HTLV-I antibody positive. This finding lends further support for a role of HTLV-I in the etiology of adult T-cell leukemia/lymphoma.     

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.     

Human T-cell leukemia virus type I or a related retrovirus in patients with mycosis fungoides/Sézary syndrome and Kaposi's sarcoma.

Antibodies reactive with human T-cell leukemia virus type I (HTLV-I) proteins p19, p24, gp46, p56, and gp68 were detected in four of 27 patients with mycosis fungoides/Sézary syndrome (MF/SS) and one patient with Kaposi's sarcoma using radioimmunoprecipitation and Western blot analysis. Seroreactivity patterns to HTLV-I proteins of MF/SS sera were indeterminate or limited in comparison with sera of patients with adult T-cell leukemia/lymphoma. HTLV-I gag- and tax/rex-specific DNA was demonstrated in peripheral blood from three of the MF/SS patients and from the patient with Kaposi's sarcoma by the polymerase chain reaction. HTLV-I-specific DNA sequences were not detected in a cohort of seven seronegative MF/SS patients. The frequency of HTLV-I infection was four of 27 or 14.8% among the MF/SS patients, which is several hundredfold higher than in normal blood donors. The present data suggest a possible association of HTLV-I or a related retrovirus with mycosis fungoides/Sézary syndrome and Kaposi's sarcoma.