Adult T-cell leukemia development from a human T-cell leukemia virus type I carrier after a living-donor liver transplantation.

Adult T-cell leukemia (ATL) develops in a human T-cell leukemia virus type I (HTLV-I) carrier. The development of malignancy during immunosuppressive treatment following organ transplantation is one of the late fatal complications. We describe the development of three cases of ATL in eight HTLV-I carriers within 164 living-donor liver transplant recipients undergoing immunosuppressive treatment. All three cases were immunosuppressed with tacrolimus. Acute-type ATL was diagnosed at 6, 9, and 25 months after living-donor liver transplantation, based on increased numbers of CD4+25+ lymphocytes exhibiting "flower-like" nuclei, and the elevation of lactate dehydrogenase. Southern blot analysis demonstrated the clonal proliferation of ATL cells in peripheral blood. The ATL cells originated from the recipient, as demonstrated by fluorescence in situ hybridization analysis using sex chromosomal markers. Our observations suggest that immunosuppressive treatment for the prevention of graft rejection after living-donor liver transplantation may induce the development of ATL in an HTLV-I carrier.

Human T-cell leukemia virus type I (HTLV-I) infection and the onset of adult T-cell leukemia (ATL).

The clinical entity of adult T-cell leukemia (ATL) was established around 1977, and human T-cell leukemia virus type 1 (HTLV-I) was subsequently identified in 1980. In the 25 years since the discovery of HTLV-I, HTLV-I infection and its associated diseases have been extensively studied, and many of their aspects have been clarified. However, the detailed mechanism of leukemogenesis remains unsolved yet, and the prognosis of ATL patients still poor because of its resistance to chemotherapy and immunodeficiency. In this review, I highlight the recent progress and remaining enigmas in HTLV-I infection and its associated diseases, especially ATL.

HTLV-1 associated adult T-cell leukemia/lymphoma in Israel: report of two patients of Romanian origin.

Human T-lymphotropic virus type 1 (HTLV-1) was the first human oncovirus isolated by Gallo et al. in 1980 and established as an etiological agent for adult T-cell leukemia/ lymphoma (ATL). Although more than 15 million individuals are infected by HTLV-1 through the world, the spread of the virus is highly endemic. The HTLV-1 infection is prevailing in southwestern Japan, inter-tropical Africa, Central and South America. In Kyushu district, Japan, the seroprevalence reaches >30% in the adult population. In the US, Europe and the Middle East the HTLV-1 infection is very rare, and cases of ATL have been reported sporadically. We describe here acute ATL in two patients of Jewish- Romanian origin. The epidemiological anamnesis and screening indicate that both patients acquired the HTLV-1 from their mothers leaving in Romania.

Human T-cell leukaemia/lymphoma virus type 1-associated infective dermatitis in Africa: a report of five cases from Senegal.

BACKGROUND: Infective dermatitis (ID) is a rare dermatological condition of childhood that has been linked to human T-cell leukaemia/lymphoma virus type 1 (HTLV-1). Most cases have been reported in the Caribbean. Although several million people are estimated to be infected by HTLV-1 in sub-Saharan Africa, no case of ID has been reported in this area. OBJECTIVES: To identify and to describe cases of HTLV-1-associated ID in Senegal, West Africa. METHODS: Over a 3-year period, a serological test for HTLV-1 was performed at a dermatological centre in Dakar, Senegal, in children who presented with a picture suggestive of ID. Complementary haematological, immunological and virological investigations were performed in infected children and in their mothers. RESULTS: Five patients with typical HTLV-1-associated ID were identified, of ages 17, 5, 4, 3 and 3 years; two patients belonged to the same family. They all presented with repeated flares of superinfected dermatitis involving typical sites of ID (mainly the scalp, external ears, nares and eyelids), associated with nasal discharge, and less commonly with a nonspecific papular rash on the face or trunk. Although oral antibiotic therapy always gave effective control of the symptoms, recurrences were constant. A persisting dry dermatitis of the retroauricular folds was common between flares. Infection in the oldest patient was associated with a chronic adult T-cell leukaemia/lymphoma. The mothers of three patients, and the grandmother of another, were all infected by HTLV-1 strains belonging to the Cosmopolitan molecular subtype, with a perfect nucleotide identity of long-terminal repeat and env gp21 genomic regions within each family. CONCLUSIONS: We present the clinical and virological features of the first reported African cases of HTLV-1-associated ID. When compared with data from the Caribbean, infectious features seemed particularly prominent. ID appears to be overlooked in sub-Saharan Africa, where it might be easily confused with common pyoderma. Breast feeding appears to be the origin of HTLV-1 contamination of the children.

Adult T-cell leukemia/lymphoma (ATLL): report of two fully documented Hellenic patients.

ATLL is etiologically associated with HTLV-I retrovirus. A population of 10 to 20 million worldwide is estimated to be infected by the virus, but only 1-4% develop ATLL during a 70-year lifespan. The latency period is more than 30 years. The aim of this study was to report two cases of ATLL in Greek patients with the concomitant study of their family members. A 55-year-old woman and a 59-year-old man presented with leucocytosis and lymphocytosis. Both were asymptomatic and physical examination was unremarkable except for minimal lymphadenopathy in the second patient. In both patients blood smears showed small-to-medium-sized, multilobulated lymphocytes, with different degrees of nuclear irregularity. Immunophenotypic study was as follows: CD2 + (97%), CD3 + (95%), CD5 + (95%), CD3/CD4 + (93%), CD3/CD25 + (84%), CD7 -/CD4 + (89%) CD2 + /HLA-DR + (53%), TCRabeta + (96%) and CD7-(7%). Bone marrow biopsy revealed a normal cellularity with dyserythropoiesis and scattered small lymphocytes (CD4 + on immunostaining) Serum HTLV I and II antibodies were positive. T-cell receptor gamma-chain rearrangement was positive in blood lymphocytes by PCR. Cytogenetic analysis showed complex karyotypic abnormalities. DNA analysis by PCR demonstrated the integration of the HTLV-I DNA in the DNA of the neoplastic T cells. Both patients rapidly developed acute type ATLL. In the first patient multiple subcutaneous nodules on the palmar surface of both hands were also observed. She received deoxycoformycin, which was stopped because of autoimmune hemolytic anemia. Corticosteroid treatment was initiated, with gradual improvement. She suffered from recurrent opportunistic infections. She is currently under interferon and zidovudine therapy with stable blood parameters. Chemotherapy was administered to the other patient with > 50% initial response. Both patients' families were tested for serum anti HTLV-I antibodies and their mates were found to be positive; they also had detectable viral DNA by PCR analysis while asymptomatic, with no abnormal clinical findings and normal white blood cell count and morphology. In conclusion, the two aforementioned patients are the first fully documented ATLL patients described in Greece. Investigation for HTLV-I antibodies should be mandatory in all patients with T-cell lymphoproliferative disorders.

PTCL: lessons from adult T-cell leukemia.

Peripheral T-cell lymphoma (PTCL) is a neoplastc disease of peripheral T-lymphocytes/NK cells, including PTCL unspecified, anaplastic large T-cell lymphoma (ALCL), IBL-like T-cell lymphoma (AILD), intestinal T-cell lymphoma (ITCL) and adult T-cell leukemia/lymphoma (ATL). The incidence of PTCL is relatively uncommon although its incidence shows significant variations in the geographical regions and racial populations. In Asia, its incidence is high due to HTLV-I infection in Japan. Molecular mechanisms of oncogenesis of PTCLs remain unknown. Therefore, analyses of ATL will give us a clue to clarify the molecular mechanism.

Adult T-cell leukemia/lymphoma: a rare case in the USA and review of the literature.

Adult T-cell leukemia/lymphoma (ATLL), in its acute stage, is a uniformly fatal disease. ATLL is caused by the human T-cell lymphotropic virus I (HTLV-1), a retrovirus endemic in numerous areas throughout the world including Japan, the Caribbean, Central and South America and certain areas of the United States. Although the progression from HTLV-1 carrier status to ATLL occurs only rarely, ATLL is incurable and thus prevention of HTLV-1 transmission should be a primary goal. With the development of new anti-retroviral and monoclonal therapies, there exist potential cures or at least prolonged remissions for patients diagnosed with ATLL. We present a case of ATLL that, to our knowledge, is only the third reported case in Georgia. In addition, we present a brief review of the literature, including potential new treatment regimens that appear to have promise in the treatment of ATLL.

Prospective investigation of transfusion transmitted infection in recipients of over 20 000 units of blood. TTI Study Group.

OBJECTIVES: To follow up recipients of 20 000 units of blood to identify any transmissions of infections through blood transfusion. DESIGN: Follow up study of recipients of transfusion. SETTING: 22 hospitals in north London. PARTICIPANT: Adult patients who had recently been transfused. MAIN OUTCOME MEASURES: Patients had further blood samples taken at 9 months that were tested for markers of hepatitis B and C and HIV and human T cell leukaemia/lymphoma virus type I or II (HTLV) infections. Recent infections were distinguished from pre-existing infections by comparison with blood samples taken before transfusion. RESULTS: 9220 patients were recruited, and 5579 recipients of 21 923 units of blood were followed up. No transfusion transmitted infections were identified. The incidence of transfusion transmitted infections was 0 in 21 043 units (95% confidence interval for risk 0 to 1 in 5706 recipients) for hepatitis B; 0 in 21 800 units (0 to 1 in 5911 recipients) for hepatitis C; 0 in 21 923 units (0 to 1 in 5944 recipients) for HIV; and 0 in 21 902 units (0 to 1 in 5939 recipients) for human T cell leukaemia/lymphoma virus. Three patients acquired hepatitis B during or after hospital admission but not through transfusion; 176 (3%) had pre-existing hepatitis B infection. Sixteen (0.29%) patients had hepatitis C, and five (0.09%) had human T cell leukaemia/lymphoma virus. CONCLUSIONS: The current risk of transfusion transmitted infections in the United Kingdom is very small, though hospital acquired infections may arise from sources other than transfusion. A considerable proportion of patients have pre-existing infections.

High prevalence of HTLV-I infection among the family members of a patient with adult T-cell leukemia/lymphoma from northeastern Japan.

Human T-cell lymphotropic virus type I (HTLV-I) is transmitted through infected lymphocytes mostly by breast feeding. In the present study, high prevalence of HTLV-I infection was disclosed in the family members of a patient with adult T-cell leukemia/lymphoma (ATL), all of whom were residents of Iwate, northeastern Japan. Long-term follow-up is necessary for people with HTLV-I infection because of the risk of developing ATL after a certain period of latency. New inventive treatments for the acute and lymphomatous types of ATL are needed.

[Adult T-cell lymphoma associated with HTLV-1: a familial form]. / Lymphome à cellules T de l'adulte associé à l'HTLV-1: une forme familiale.

BACKGROUND: Adult T-cell leukemia-lymphoma (ATL) can occur in siblings infected with HTLV-1. CASE REPORTS: Two Caribbean siblings developed ATL a few years apart. One case has been reported previously. Both individuals had peripheral lymph node T-cell lymphoma and a few atypical lymphocytes on blood smear. Lymphocytosis, bone marrow biopsy, abdominal computed tomographic scanning, and chest radiography were normal. Clonal rearrangement of T-cell receptor was present in skin lesions for both patients and in the blood for one. HTLV-1 serology was positive. Clonal integration of HTLV-1 provirus was demonstrated in skin lesions in one patient and in blood lymphocytes in the other. Chemotherapy, then interferon alpha, were unsuccessful in the first patient. Topical metchloretamine was partially effective for the second patient. DISCUSSION: ATL in siblings is explained by mother-to-child transmission of HTLV-1 infection during breastfeeding.

Intrafamilial clustering and 4-year follow-up of asymptomatic human T-cell leukaemia virus type I (HTLV-I) infection in Benin (West Africa).

BACKGROUND: Few data exist concerning familial human T-cell leukaemia virus type I (HTLV-I) carrier states and transmission in African countries. Two previous surveys performed in Benin in 1989 and 1990 using a three-level cluster sampling method allowed us to identify HTLV-I positive subjects. The evolution of HTLV-I within the families of these subjects is described over a 4-year period, 1991-1995. METHODS: Since 1991, 37 HTLV-I seropositive subjects, six subjects with indeterminate Western-Blot pattern, and their relatives have been followed up once a year clinically and biologically. RESULTS: Twenty-three mothers in the study group gave birth to 27 children between 1991 and 1995. Among the 13 infants born to the 12 seropositive mothers, two seroconverted before their second birthday. One adult woman whose husband was seropositive developed seropositivity 4 years after marriage. In March 1992, a family case-control study (proband study) was conducted. A seroprevalence of 27.5% was found among 138 relatives of 32 infected subjects and 1.4% among 142 relatives of 32 control subjects. CONCLUSIONS: There is clearly an intrafamilial clustering of HTLV-I in Benin. The annual incidence density of HTLV-I in this cohort is estimated at 6 per thousand.

Familial transmission of human T-lymphotropic virus type 1 (HTLV-1) in patients with adult T-cell leukemia/lymphoma or HTLV-1-associated myelopathy.

The seroprevalence of human T-lymphotropic virus type 1 (HTLV-1) in Taiwan is 0.48%. In this study, we investigated the patterns of intrafamilial transmission of HTLV-1 in Taiwanese patients with adult T-cell leukemia/lymphoma (ATL/L) or tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). Fifteen index patients (9 men, 6 women, aged 31-71 yr), 13 with ATL/L, and two with TSP/HAM, and 98 relatives were included. Of the 98 relatives, 23 were seropositive for HTLV-1. Spouses of 11 patients were studied. Seven of eight wives of male patients but none of the three husbands of female patients were HTLV-1 carriers. Mother-to-child transmission was found in seven of 13 families and in 15 of 75 children tested. The correlation of breast-feeding with seropositivity in two families with seropositive mothers indicates its important role in vertical transmission of HTLV-1. Our findings suggest that husband-to-wife and mother-to-child transmission are the main forms of intrafamilial transmission of HTLV-1 in Taiwan, a nonendemic area. Screening for HTLV-1 in family members of patients with ATL/L or TSP/HAM, and seropositive blood donors, may be warranted. Seropositive individuals should be educated to prevent the spread of the virus through sexual contact and breast feeding.

Pathogenesis and prevention of HTLV-1-associated diseases.

HTLV-1 is an important factor involved in various diseases including adult T-cell leukemia/lymphoma and HTLV-1 associated myelopathy/tropical spastic paraparesis. Amount of HTLV-1 provirus integrated in human peripheral blood mononuclear cells might be a candidate for a risk factor in the manifestation of HTLV-1 associated diseases. Experimental animal models would be useful to dissect the pathogenesis of HTLV-1 associated diseases. We present rat and mouse models of HTLV-1 infection. Using these animal models, we could clarify the intrauterine transmission of HTLV-1, and have found that both genetic background and HTLV-1 infection are important in pathogenesis of HAM/TSP-like rats. We also discuss the preventive measures of HTLV-1 transmission by use of antisense oligonucleotides.