A 17-Year-Old Boy With Right Face Palsy, Left Leg Weakness, and Lytic Skull-Bone Lesions.

Human T-cell lymphotropic virus (HTLV), an infection that is endemic in certain parts of Asia, Africa, and South America, has been associated with malignancy and neurological deficits. Here, we describe a pediatric patient with chronic HTLV-I infection who developed complications associated with HTLV-I (ie, adult T-cell leukemia/lymphoma and HTLV-I-associated myelopathy/tropical spastic paraparesis). To our knowledge, this presentation in a child has never been described. The patient underwent a bone marrow transplant and, at the time of this writing, was in remission. This case report highlights the fact that HTLV-related complications, previously expected to occur after decades of infection, also can occur in pediatric patients, particularly those who acquired HTLV-I perinatally.

Human T-cell leukemia virus (HTLV)-associated neuropathy.

Symptomatic peripheral neuropathy occurs in a small proportion of HTLV-1 infected patients. Peripheral manifestations are often masked by symptoms and signs of the tropical spastic myelopathy characteristic of the disease. Peripheral neuropathy is often characterized by alteration of small-fiber functions, with inflammatory lesions of peripheral nerves, sometimes associated with symptomatic polymyositis, which may occur in isolation in this setting.

The 14th International Conference on Human Retrovirology: HTLV and related retroviruses (July 1-4, 2009; Salvador, Brazil).

The "14th International Conference on Human Retrovirology: HTLV and Related Retroviruses" was held in Salvador, Bahia, from July 1st to July 4th 2009. The aim of this biennial meeting is to promote discussion and share new findings between researchers and clinicians for the benefit of patients infected by human T-lymphotropic virus (HTLV). HTLV infects approximately 15-20 million individuals worldwide and causes a broad spectrum of diseases including neurodegeneration and leukemia. The scientific program included a breadth of HTLV research topics: epidemiology, host immune response, basic mechanisms of protein function, virology, pathogenesis, clinical aspects and treatment. Exciting new findings were presented in these different fields, and the new advances have led to novel clinical trials. Here, highlights from this conference are summarized.

[Influence of antisense RNA and sequences of viral transactivators traps on RNA synthesis of HTLV-1 virus].

Significant number of scientific publications devoted to inhibition of viral replication by antisense RNA (asRNA) genes shows that this approach is useful for gene therapy of viral infections. To investigate the possibility of suppression of HTLV-1 virus reproduction by asRNA we constructed recombinant plasmids containing asRNA genes against U3 long terminal repeats region and X gene under the control of promoter of myeloproliferative sarcoma virus (MPSV) or without such promoter. Using stable calcium-phosphate transfection method with subsequent selection in the presence of G-418, RaHOS line-based cell clones carrying both asRNA genes and sequences able to bind HTLV-1 transactivator proteins (i.e. "traps" of viral transactivators, TVT) were obtained. Data from dot-hybridization analysis of viral RNA extracted from RaHOS cell clones showed that TVT sequences are able to suppress the viral RNA synthesis on 90% and asRNA against X gene synthesis--on 50%.

[Guide of clinical management of HTLV patient: neurological aspects]. / Guia de manejo clínico do paciente com HTLV: aspectos neurológicos.

The Brazilian Ministry of Health (STD and Aids Program) invited specialists to make up an informative guide to deal with HTLV patients. Among the different topics, the neurological aspects associated to HTLV were contemplated. A suspected case should include changes in force and reflexes, distal paresthesiae and autonomic dysfunction. The investigation of such case should be based on the syndrome shown by the patient. For patients with spinal cord syndrome, magnetic resonance imaging or myelography as well as spinal fluid studies should be carried out. For patients with neuropathic or myopathic syndrome, electroneuromyography and CPK dosing should be done, and for those with autonomic syndrome, a search for postural hypotension, ultrasonography of urinary tract and urodynamic studies should be requested. The treatment may be symptomatic (spasticity, neurogenic bladder, intestinal constipation and neuropathic pain) and specific to be carried out in specialized centers.

Guia de manejo clínico do paciente com HTLV: aspectos neurológicos / Guide of clinical management of HTLV patient: neurological aspects

O Ministério da Saúde (Programa DST e Aids) reuniu especialistas para elaborar um guia informativo de manejo do paciente com HTLV. Dentre os diferentes tópicos, foram contemplados os aspectos neurológicos associados à infecção pelo HTLV. Um caso suspeito de doença neurológica associada ao HTLV deve incluir alteração de força e reflexos, parestesias distais e disfunção autonômica. A investigação do caso suspeito deve ser baseada na síndrome exibida pelo paciente. Para o paciente com síndrome medular, deve-se solicitar ressonância magnética da medula ou mielografia, assim como, estudo do líquor. Para o paciente com síndrome neuropática ou miopática, deve-se solicitar eletroneuromiografia e dosagem de CPK, e para aquele com síndrome autonômica, pesquisa de hipotensão postural, ultrassonografia das vias urinárias e estudo urodinâmico. O tratamento pode ser sintomático (espasticidade, bexiga neurogênica, constipação intestinal e dor neuropática) e específico a ser feito em centros especializados.

Plasmapheresis in treatment of human T-lymphotropic virus type-I associated myelopathy.

In 11 of 18 patients with human T-lymphotropic virus type-I (HTLV-I) associated myelopathy (HAM) gait, sensory, and/or sphincter disturbance improved with plasmapheresis (4 to 6 sessions in 2 weeks), and the effects were maintained for 2 to 4 weeks. Plasmapheresis lowered the titre of HTLV-I antibody in serum but not in cerebrospinal fluid, and change of HTLV-I antibody titres did not correlate with the effects of plasmapheresis. These results suggest that plasmapheresis is useful treatment, at least in producing a temporary improvement, in patients with HAM, and that some humoral factor(s), but not HTLV-I antibody, may be important in the pathogenesis of HAM.

Manifestations of human T-lymphotropic virus type I infection.

HTLV-I, the first human oncovirus, is a type C retrovirus linked to the development of ATLL. The virus shows a striking ethnogeographic distribution that is only partially understood. Certain populations at high risk for AIDS appear to have a higher incidence of HTLV-I infection. The extended latent period renders present knowledge of the sequelae and natural history of HTLV-I seropositivity incomplete, although recent data suggest that HTLV-I infection may have important implications for blood transfusion, organ transfer, and public health policy. A variety of clinical syndromes have been associated with infection, ranging from an asymptomatic carrier state to acute ATLL with lymphadenopathy, hepatosplenomegaly, hypercalcemia, cutaneous lesions, and systemic immunosuppression. Conventional chemotherapy is marginally effective; innovative approaches to therapy are presently being evaluated.

The role of the multichain IL-2 receptor complex in the control of normal and malignant T-cell proliferation.

Antigen-induced activation of resting T cells induces the synthesis of interleukin-2 (IL-2), as well as the expression of specific cell surface receptors for this lymphokine. There are at least two forms of the cellular receptors for IL-2, one with a very high affinity and the other with a lower affinity. We have identified two IL-2 binding peptides, a 55-kd peptide reactive with the anti-Tac monoclonal antibody and a 75-kd non-Tac IL-2 binding peptide. Cell lines bearing either the p55, Tac, or the p75 peptide alone manifested low-affinity IL-2 binding, whereas cell lines bearing both peptides manifested both high- and low-affinity receptors. Fusion of cell membranes from low-affinity IL-2 binding cells bearing the Tac peptide alone with membranes from a cell line bearing the p75 peptide alone generated hybrid membranes bearing high-affinity receptors. We propose a multichain model for the high-affinity IL-2 receptor in which both the p55 Tac and the p75 IL-2 binding peptides are associated in a receptor complex. The p75 peptide is the receptor for IL-2 on large granular lymphocytes and is sufficient for the IL-2 activation of these cells. In contrast to resting T cells, human T-cell lymphotropic virus I-associated adult T-cell leukemia cells constitutively express large numbers of IL-2 receptors. Because IL-2 receptors are present on the malignant T cells but not on normal resting cells, clinical trials have been initiated in which patients with adult T-cell leukemia are being treated with either unmodified or toxin-conjugated forms of anti-Tac monoclonal antibody directed toward this growth factor receptor.

[Clinical studies on interferon in cancer therapy in Japan].

Since the late 1970s, 18 clinical studies have been conducted in Japan with various types of human interferon (IFN) for their possible anti-tumor efficacy under the control of the Special Committee for Clinical Application of IFN of the Ministry of Health and Welfare. Objective antitumor effects have been observed in renal cell carcinoma, brain tumor, multiple myeloma, malignant lymphoma, adult T cell leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, and by local injections in skin cancer such as malignant melanoma and cutaneous lymphoma. In this paper, updated results of clinical studies of the 3 types of IFNson various malignant tumors in Japan was reviewed, and the potential usefulness of IFNs as the first cytokine introduced into a clinical trial of the treatment of cancer was discussed.

Recombinant interferon beta and gamma in the treatment of adult T-cell leukemia.

Adult T-cell leukemia (ATL) is one of the most difficult diseases to treat because of severe underlying immune deficiency and metabolic disturbance. Interferon has potent antiviral, antiproliferative, and immunomodulating properties, and therefore, this may be a good agent to treat such immune deficient patients with peripheral T-cell leukemia. During a period from April 1984 to August 1985, six patients were treated with interferon-beta (IFN-beta), and interferon-gamma (IFN-gamma) was given to five patients. Three patients achieved partial remission by IFN-beta administration with a response duration of 1, 1.5, and 12 months respectively, whereas one complete remission and two partial responses were experienced by IFN-gamma treatment with 4, 4, and 2 months of response. Side effects of IFN-beta were similar to those of IFN-gamma including fever, chills, fatigue, mild hematologic depression, and transient hepatic enzyme abnormalities. These promising results warrant further well-designed clinical trials including combination with other agents or modalities of treatment.

A case of CD4+/CD8- adult T-cell leukemia with good response to interferon-beta terminating as a CD4+/CD8+ adult T-cell lymphoma.

The leukemic cells of adult T-cell leukemia (ATL) usually express the helper/inducer associated antigen reactive with anti-CD4 antibodies but not with anti-CD8. We present a 63-yr-old woman with ATL characterized by circulating leukemic cells with CD4+/CD8- phenotype, hepatosplenomegaly with no lymphadenopathy, and the presence of proviral DNA of human T-cell leukemia virus I in the leukemic cells. She was successfully treated with interferon beta and the remission lasted for 12 months. She then relapsed in the lymph nodes with minimal peripheral blood involvement. The neoplastic cells of the lymph node now co-expressed CD4 and CD8 antigens indicating that the change in clinical manifestation was accompanied by a phenotypic change of the leukemic cells.

Adult T cell leukaemia/lymphoma.

Adult T cell leukaemia/lymphoma was first identified by Japanese investigators in the mid 1970s. Distinctive characteristics include hypercalcaemia, metabolic bone disease, opportunistic infections and evidence of multiorgan involvement. The malignant cell has the surface phenotype of a T helper lymphocyte but functions as a T suppressor cell, and in leukaemic patients this cell usually has a unique multilobed appearance, which may aid in recognizing the disease. The overwhelming majority of patients with ATLL originate from the south-west Japanese archipelago, as well as the Caribbean basin and south-east USA. The geographic localization of this disease is the result of the endemic distribution of the human retrovirus (HTLV-I) which has been established as the cause of ATLL. Infection with this virus may result in no disease (asymptomatic carriers) or ATLL. While ATLL usually pursues an acute or subacute (prototypic) course, patients are also seen with 'chronic' or 'smouldering' disease. Over time, these more indolent variations may progress to the prototypic form. When aggressive, ATLL must be treated with intense combinations of cytotoxic drugs similar to those used to treat the more common B cell lymphoproliferative disorders. Even though half of the patients treated achieve a remission, the duration is usually brief and the overall actuarial median survival is only 11 months. In addition to recurrent disease, these patients frequently succumb to opportunistic infections.