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 malignant studies, little prospective information on the risk of developing ATL among persons with HTLV-I infection is available. We present here a model of 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« 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 percent for males and 4.2 percent 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. (AU)

Molecular epidemiology of HTLV-I-associated non-Hodgkin's lymphomas in Jamaica

As part of epidemiologic studies of human T-lymphotropic virus (HTLV)-I-associated malignancies in Jamaica, the authors evaluated 26 patients with non-Hodgkin's lymphoma for the presence of integrated HTLV-I provirus in their malignant cells. Fifteen of 26 patients had integrated provirus. All 15 also were HTLV-I antibody positive. Eleven patients did not have integrated provirus, and all 11 were antibody negative. All of the antibody-positive cases had onset of their disease in adulthood (age range, 21-57 years) as opposed to the broad age range of negative cases (4-66 years). Clinical features which were more common in provirus positive than negative patients included leukemic phase, skin involvement, and hypercalcemia, which are all features frequently seen in HTLV-I-associated adult T-cell leukemia/lymphoma (ATLL). The presence of skin involvement, circulating malignant cells, abnormal liver function tests, or the presence of two or more of these four features were statistically significantly different between virus-positive and virus-negative cases. Although the survival of positive cases (6 months) was shorter than that of negative cases (9 months), this was not statistically significant. The only significant determinant of survival was hypercalcemia, with those who developed hypercalcemia at some point in their disease course, independent of their HTLV-I status, surviving a mean of 5 months as compared to a mean of 17.5 months in those who never became hypercalcemic. The six HTLV-I-positive lymphomas that underwent cell typing were all primarily OKT4 positive, whereas two HTLV-I antibody-negative cases that were typed were B-cell lymphomas. (AU)

A case control study of adult T-cell leukaemia/lymphoma and human T-lymphotropic virus type I in Jamaica - abstract

Ninety-three patients with haematological malignancies were enrolled into the study between Janauary, 1984 and August, 1985. Of these, 23 fulfilled the clinicopathological criteria for the diagnosis of adult T-cell leukaemia/lymphoma (ATL). Eighteen of 23 ATL patients were HTLV-I seropositive, compared with 8 of 46 age- and sex-matched general medical controls, resulting in a claculated odds ratio (estimated relative risk) of 17:1. Other patients with non-Hodgkin's lymphoma had slightly higher seropositivity rates than the controls, but none of the other haematological malignancies were HTLV-I positive. No other risk factors for ATL were conclusively demonstrated. The recently noted association of HTLV-I with tropical spastic paraparesis (Jamaican neuropathy) was supported by a high level of HTLV-I antibodies among patients with certain neurological disorders (AU)

Non-hodgkin lymphoma in Jamaica and its relation to adult T-cell leukemia-lymphoma [published erratum appears in Ann Intern Med 1987 Jun;106(6):917]

Of 95 patients consecutively diagnosed with non-hodgkin lymphoma, 52(55 percent) had antibodies to human T-cell leukemia-lymphoma virus, type I. Antibody positively was strongly associated with skin involvement, leukemia, and hypercalcemia (p<0.02). Two patients had systemic opportunistic infections. Neither meningeal nor lung infiltration was detected, and lymph node infiltration was diffuse in all patients. Of 36 patients who received immunophenotypic classifications, 30 had diseases that affected the T-cell system, and the cells of all tested patients with these diseases showed the helper/inducer (T4) phenotype. Twenty-seven of these thirty-six patients were found to have adult T-cell leukemia-lymphoma, and of the 27, 24 had antibodies to HTLV-I. The median duration of survival in patients with adult T-cell leukemia-lymphoma was 17 weeks, but a subgroup of 81 weeks, which suggests that the disease has differing expression with courses that range from smoldering and indolent to acute and rapidly fatal. Hypercalcemia was the most important prognostic determinnant of adult T-cell leukemia-lymphoma.(AU)

Immunology of non-hodgkin's lymphoma in Jamaica - abstract

This study was undertaken to determine the immunological profile of non-Hodgkin's lymphoma (NHL) patients in Jamaica. Immunoperoxidase (IP) and immunofluorescence (IF) techniques were used, employing a panel of monoclonal antibodies, to detect T and B lymphocytes and their subjects in lymph nodes and cell suspensions obtained from 22 patients diagnosed consecutively from January, 1985. Results of immunological typing were compared with results of HTLV-1 (Human T-cell lymphotropic virus type I) antibody testing, and with the histological pattern. Sixteen of the patients (73 percent) had T-cell disease and 4 had B-cell disease. Results were equivocal or unsatisfactory in 2 patients. Fourteen who had T-cell disease were further subtyped. Thirteen had the helper-inducer phenotype and 1 had the cytotoxic-suppressor phenotype. There was close agreement between the results of IP typing of lymph nodes and cell suspensions, and of IF typing of cell suspensions, 15 (12 T-cell and 3 B-cell) of the 20 patients tested showing identical results. Three patients who were typed as T-cell disease by the IP technique were typed as normal or immunosuppressed by the IF technique. However, the IP typing was done before, and the IF was done after, treatment. Discrepancies in the results for 2 patients are unexplained. Eight of the 14 patients with T-cell disease for whom results of HTLV-I antibody testing are available are HTLV-I antibody-positive. Both of the patients with B-cell disease for whom these results are available are antibody-negative. There was no correlation between lymphocyte phenotype and histological pattern (AU)

Seroepidemiologic studies of human T-cell leukemia/lymphoma virus type 1 in Jamaica

The prevalence of HTLV-1 antibodies was evaluated in Jamaica among persons with various malignant, infectious, autoimmune and hematologic disorders and in clinically normal persons. Results document that: (1) the prevalence of HTLV-I antibodies in this population increases with age; (2) overall, there is no significant difference in the antibody prevalence between females and males: (3) antibody-positive individuals are born in all major regions of the island and geographical variance in antibody prevalence by place of birth was not prominent; (4) there is further confirmation of the high prevalence of HTLV-I antibody-positive lymphomas in Jamaica; and (5) the prevalence of HTLV-I antibodies in hemophiliacs, patients with chronic lymphocytic leukemia (CLL0, myelogenous leukemias, and patients with breast cancer is higher than in age-matched populations without malignancies, although none of these differences were statistically significant. The increased prevelence in hemophiliacs is most likely related to their frequent transfusion with blood products, but it has not yet been determined whether the prevalence in patients with other diseases is related to their disease or other as yet undefined factors in common. (Au)

Skin manifestations of HTLV-associated adult T-cell lymphoma/leukaemia in Jamaica - abstract

A prospective study was conducted on 56 consecutive patients with the diagnosis of non-Hodgkins lymphoma (NHL) who presented between February 1982 and April 1984. The aims were to determine the frequency of skin involvement in patients with NHL and in particular those NHL patients who were also in HTLV-positive and satisfied the criteria for adult T-cell lymphoma-leukaemia (ATL) to characterise the types of skin lesions, to determine the relationship of skin involvements to course and prognosis and to determine whether any differences existed in the skin manifestations of HTLV positive and HTLV negative patients. Skin biopsies and skin scrapings for microscopy and culture were done where indicated, as well as HTLV antibody assays. Thirty-one patients (62 percent) were HTLV-positive, 16 males and 15 females. Their ages ranged from 20 to 63 with an average age of 41 years. Twenty (65 percent) had probable ATL and 7 (23 percent) possible ATL. Twelve of the 20 probable ATL had skin involvement. Fifty per cent (6/12) had skin lesions at initial presentation. The other 6 developed lesions during the course of their illness from 6 weeks to 1 year after diagnosis. The commonest type of skin lesion was generalized papulonodular in 50 percent of patients. Pruritus was present in 25 percent of patients. The median survival was 6 months in patients with skin involvement and 2 months in patients without - an insignificant difference statistically. Crusted scabies was found in 5/12 (42 percent) of the ATL patients and was recurrent in 3 patients. These results confirm that ATL is HTLV-associated, commonly presents with skin lesions, but is quite different from the two classical cutaneous lymphomas of the skin, mycosis fungoides and the Sezary's syndrome, in both morphology of the skin lesions and course and prognosis of the disease, the course of ATL being short and explosive with hypercalcaemia rather than skin lesions being the most important diagnostic factor (AU)

Infection in human T-cell lymphoma virus (HTLV)-positive and HLTV-negative lymphoma in Jamaica - abstract

Systematic opportunistic infections occur in approximately 20 percent of cases of HTLV-positive lymphoma seen in Japan and the South-Eastern United States. In a study conducted between February 1, 1982 and January 31, 1984, 38 cases of lymphoma diagnosed at the University Hospital, Jamaica, were reviewed to determine the types of infections that occurred in these patients. Sixteen of 23 (60 percent) and 11 of 15 (73 percent), HTLV-positive and HTLV-negative patients respectively developed one or more infectious episodes during their illness. In the HTLV-positive group, there were 36 such episodes, while 23 occurred in the negative group. Five each of HTLV-positive and negative patients had only one infectious episode while the remainder had 2 or more. The pattern of infections was similar in both groups with septicaemia, skin, buccal cavity, lung and urinary tract being the most common sites of infection. Severe infections accounted for 13 of the 36 (36 percent) infectious complications in the HTLV-positive patients and in 8 of the 23 (35 percent) episodes in the HTLV-negative group. Six of 36 (17 percent) and 13 of 23 (56 percent) infectious episodes were associated with severe neutropenia. Immunoglobulins were normal in those patients in whom this was done. Bacterial infection was the most common cause of infections in both groups; however, gram negative bacilli (GNB) were found more frequently in the positive than in the negative group. Salmonella septicaemia occurred in one HTLV-positive and one HTLV-negative patient. Fungal infections occurred on 8 (25 percent) and 2 (6 percent) occasions and viral infection on 1 (4 percent) and 2 (9 percent) occasions in HTLV-positive and negative patients respectively. Fungal infection in all but one case confined to skin and buccal cavity in both groups. The one exception had a fungal lung abscess and this was in an HTLV-positive patient. Thus only 4 percent of HTLV-positive patients had systemic opportunistic infections. Scabies occurred in 2 (6 percent) HTLV-positive patients and one (4 percent) HTLV-negative patient. Systemic opportunistic infections are therefore uncommon in Jamaican patients with HTLV-associated lymphoma, unlike the situation in other endemic areas. Death was directly attributable to infection in 8 (35 percent) HTLV-positive and 6 (40 percent) HTLV-negative patients. GNB septicaemia was the most common cause of death in the HTLV-positive group (AU)

Anti-tac antibody and the diagnosis of adult T-cell leukaemia/lymphoma (ATL) - abstract

Activated T-cells express Tac antigen (defined by anti-Tac monoclonal antibody) whereas resting T-cells, B-cells and monocytes do not express this antibody. Tac-antigen is probably a T-cell growth factor receptor. As T-cells are activated in vivo by infection with Human T-cell leukaemia/lymphoma virus (HTLV), we have evaluated the usefulness of measuring Tac-antigen to detect patients with adult T-cell leukaemia/lymphoma. Tac-antigen was demonstrable in 8 of 11 patients who had clinical features typical of, or suggesting, adult T-cell leukaemia/lymphoma (ATL). Six of these patients were human T-cell leukaemia/lymphoma virus type 1 (HTLV-1) antibody positive and 2 were HTLV-1 antibody negative. One of the HTLV-1 antibody positive patients who had features of ATL but was Tac negative was immuno-suppressed at the time of the analyses. One HTLV-antibody positive who did not have features of ATL was Tac positive. Follow-up of such patients will demonstrate if they eventually develop the clinical features of ATL. We conclude that anti-Tac antibody is a useful marker for ATL (AU)

Clinical features of non-Hodgkin's Lymphoma in Jamaica

The clinical features of 95 patients with non-Hodgkin's Lymphoma (NHL) seen at the University Hospital of the West Indies (UHWI) during a 10-year period are reviewed. The overall male: female ratio was 1.3:1, but in patients under 50 years of age the disease occurred equally in men and women whereas, over 50, there were slightly more men than women (1.8:1). The majority of patients presented with advanced disease. Lymphadenopathy was the most common presenting feature. Hypercalcaemia, leukaemia spill and skin lesions occurred frequently, and most patients with non-Hodgkin's lymphoma showed a diffuse histological pattern. These features are typical of adult T-cell lymphoma/lukeaemia (ATL), and may reflect the high incidence of human T-cell lymphoma virus (HTLV) in Jamaica. Anaemia, hypoalbuminaemia and infections occurred commonly at presentation or during the course of the disease. Important differences are noted between the clinical features of NHL in Jamaica and elsewhere (AU)

Adult T-cell leukemia/lymphoma in Jamaica and its relationship to human T-cell leukemia/lymphoma virus type I-associated lymphoproliferative disease

We had shown previously that the prevalence of human T-cell leukemia/lymphoma virus type I (HTLV-I) antibody positivity is high in Jamaican non-Hodgkin's lymphoma (NHL) patients and that virus-positive patients have the clinical features and poor prognosis of adult T-cell leukemia/lymphoma (ATL). 62 percent of 45 NHL patients diagnosed consecutively between 2/1/82 and 1/31/84 and studied prospectively were HTLV-I-antibody positive. Skin involvement (38 percent), hypercalecemia (44 percent), and leukemia (40 percent) were unusually prevalent and there was a strong association (p < 0.05) with HTLV-I-antibody positivity. 52 percent of the patients had bone marrow infiltration, and 74 percent of these patients were HTLV-I-antibody positive (p=.06). Lymphadenopathy (96 percent), hepatomegaly (60 percent), and splenomegaly (25 percent) were detected with about the same frequency as in other series of NHL patients with advanced disease, and 61-88 percent of these patients were HTLV-I-antibody positive. Patients were classified into those with "typical ATL" (NHL associated with 2 of the 4 features) i) hypercalecemia; ii) histologically proven skin infiltration; iii) leukemia; and iv) bone marrow infiltration, providing that the morphology of infiltrating of leukemic cells was characteristic of ATL; those "consistent with ATL" (NHL associated with 1 of these 4 features); and "non-ATL" (NHL without any of these 4 additional features). Thirty-two (71 percent) of the NHL patients were ATL patients, i.e. had features typical of or consistent with ATL, and 78 percent of these were HTLV-I-antibody positive. HTLV-I provirus was detected in tumour cells of all HTLV-I-antibody positive patients tested. Three (23 percent) of the non-ATL patients were HTLV-I-antibody positive. There was no correlation between histopathological features and the clinical classification of HTLV-I-antibody positivity. Median survival of ATL and non-ATL patients was 16 and 53 weeks. Although the disease was unusually fulminant, 34 percent of the ATL patients had a subacute or chronic course. Skin involvement and leukemia were prominent in these patients. Hypercalecemia was the chief prognostic determinant. Median < 0.05). Hypercalecemia caused 10 deaths, infections 12, and death was due to tumour progression in 4 patients. Infections were usually due to pyogenic organisms and only 2 patients had systemic opportunistic infections. Six (27 percent) of 22 chronic lymphocytic leukemia (CLL) patients were HTLV-I-antibody positive. (AU)

Surface markers in lymphoproliferative disorders in Jamaica - abstract

No data have been reported on surface marker studies on haematological malignancies in the Commonwealth Caribbean. Surface marker studies were performed on 14 patients with non-Hodgkin's lymphoma (NHL) and eleven patients with chronic lymphocytic leukaemia (CLL) using rosetting and immunofluorescent techniques on lymphocytes separated by a density gradient flotation method. Twelve of the 14 NHL patients had T-cell disease, indicating that the cell origin of NHL in Jamaica differs from that reported in North America or Europe, where B-cell disease predominates. Nine of 11 were HTLV-antibody-positive, suggesting that they had adult T-cell leukaemia/lymphoma. Ten of the 11 CLL patients had B-Cll, similar to findings elsewhere. However, the frequency of HTLV-antibody-positivity was unexpectedly high in this group (35 percent) and a virus has been isolated from the T-cells of one of the B-CLL patients (AU)

Human T-Cell leukaemia/lymphoma virus-associated lymphoreticular neoplasia in Jamaica

19 (34 percent ) of 56 Jamaicans with lymphoproliferative neoplasia had antibody to the human t-cell leukemia/lymphoma virus (HTLV) in their sera. 17 of those positive had either non-Hodgkin's lymphoma (NHL) or chronic lynphocytic leukemia. Of 16 consecutive patients presenting with NHL 11 (69 percent ) were HTLV seropositive. Virus-positive patients with NHL, among whom females were over-represented, had the clinical features and poor survival typical of adult T-cell leukemia/lymphoma. HTLV-associated leukemia/lymphoma is a distinct clinicopathological entity, and the high incidence in this series suggests that HTLV is an important cause of lymphoreticular neoplasia in Jamaica (AU)

The human T-cell leukemia/lymphoma virus (HTLV) and lymphoproliferative malignancies in Jamaica - abstract

The human T-cell leukemia/lymphoma virus (HTLV) is a type-C retrovirus recently isolated from patients with adult T-cell lymphoma. The prevalence of viral infection was determined in patients attending the Hematology Clinic at the University Hospital of the West Indies by using a radioimmunoassay for HTLV antigen and a radioimmune precipitation assay for the viral core antigen (A Antigen). Antibody has been detected in 7 of the first 40 patients tested - 3/8 with non-Hodgkin's lymphoma (NHL); 3/9 with chronic lymphocytic leukemia (CLL); and the only patient in the group who had acute lymphoblastic leukemia (ALL). The tests were negative in 4 patients with myeloma; 4 with pernicious anemia and 14 other patients with a variety of other disorders. The three patients with NHL had lymphadenopathy and hepatomegaly on presentation. Two had splenomegaly and one had skin involvement. Two were hypercalcaemic at presentation and the third became hypercalcaemic soon after admission. Large cells with abundant cytoplasm and convoluted nuclei predominated in the blood of two patients in whom bone marrow infiltration was also demonstrable. The histological appearances varied, but large non-cleave cells predominated. Survival was short (two weeks to one month) and there was poor response to chemotherapy. The HTLV-positive patients who had CLL and ALL showed clinical and hematological features typical of these disorders. Further work is being done to try to define more clearly the role of this viruse in causing lymphoproliferative disorders (AU)

Non-Hodgkin's lymphoma in Jamaica: a ten year experience - abstract

In the period January 1969 - July 1979, 235 cases of Non-Hodgkin's Lymphoma (NHL) were seen at the University Hospital of the West Indies. Of these cases 95 were sufficiently documented to be available for study. There were 53 Males and 42 females among these patients. The median age at presentation was 47 years. Of the 95 patients, 6 (6 percent) were stage I or II at presentation while 89 (94 percent) presetned in stages III or IV. 76 of these cases (80 percent), were stage IV. A haemoglobin (Hb) concentration of less than 12 g/dl was noted in 44 patients (46 percent) when they were first admitted, with 15 (16 percent) having a haemoglobin value of less than 9 g/dl. The bone marrow was infiltrated in 38 of 72 patients (53 percent) who had this investigation done. The skin was involved with lymphoma in 20 patients (21 percent) and a leukaemic spill was seen in 18 patients (19 percent). Hypercalcaemia was present in 17 of 70 cases (24 percent) in whom this investigation was performed at first contact and a further 2 patients developed this complication during the course of their disease. Scabies was a presenting feature or developed during the illness in 8 (8.4 percent) patients. CNS infiltration was seen in only 2 patients (2.1 percent). Infections developed in 35 patients (37 percent) of which 29 were bacterial, 4 fungal and 2 unknown. Of 79 patients in whom it was documented, a complete remission was noted in 15 (19 percent), partial remission in 25 (32 percent) and no response to therapy was seen in 39 (49 percent) patients. Twenty-nine patients were lost to follow-up. Of the remaining 66 patients. 57 had died during the period of study with a range of survival of 1 - 238 weeks from diagnosis. The median duration of survival was less than 20 weeks (AU)