Human T-cell leukemia virus type 1 (HTLV-1), a double-stranded RNA retrovirus, has been demonstrated to be the causative agent in the development of adult T-cell leukemia/lymphoma (ATL/L). HTLV-1 infection is endemic in the southwestern part of Japan and the Caribbean basin, with geographic clusters reported in Africa, Central and South America, the Middle East, and the southeastern United States.1

The majority of individuals infected with HTLV-1 are asymptomatic carriers; however, a proportion will develop either ATL/L or a chronic inflammatory syndrome [e.g., HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), polymyositis, arthropathy, infective dermatitis, and uveitis].2-7 The lifetime risk of an HTLV-1 carrier developing either ATL or HAM/TSP is 1-5% and 1-2%, respectively.8-11 ATL occurs only after a long latency period, ranging from 10 to 30 years, with the accumulation of additional oncogenic events.12-14

Four criteria need to be fulfilled in order to make the diagnosis of ATL: (1) histologically and/or cytologi-cally proven T-cell lymphoid malignancies (i.e., usually expression of CD2, CD3, CD4, and CD5 with absent CD7 and CD8), (2) abnormal T lymphocytes consistently present in the peripheral blood, except in the lymphoma type (i.e., flower cells and/or small and mature T lymphocytes with incised or lobulated nucleus), (3) seropositivity for HTLV-1 (by indirect immunofluorescence, enzyme-linked immunosorbent assay, passive hemagglutination, or Western blot), and (4) clonal integration of proviral DNA into the cellular DNA of neoplastic T cells [by Southern blot analysis, polymerase chain reaction (PCR), or inverse PCR].15-19 ATL is classified into four clinical subtypes (i.e., acute, lymphoma, chronic, or smouldering) with different prognoses and outcomes (Table 63.1). Because of the heterogeneous outcomes, even within a subtype, it may be prudent to stratify all patients into high- and low-risk groups at the time of diagnosis on the basis of the following poor prognostic features: hypercalcemia, elevated levels of serum lactate dehydrogenase, poor performance status, age over 40 years, and multiple sites of disease.16 Patients with low-, standard high-, and extremely high risk disease had median survival times of 37, 8, and 2.4 months, respectively.16 Other features that have been associated with a poor outcome and/or progression from smouldering or chronic ATL to acute ATL include poor performance status, increased serum creatinine, high white blood cell count, microsatellite instability, high expression of the proliferation marker Ki-67, unusual immunophenotype, integration of a defective HTLV-1 provirus, deletions of p15 and/or p16 genes, and high serum thymidine kinase, serum soluble interleukin 2 receptor (IL-2R), serum ^-microglobulin, or serum parathyroid hormone-related protein lev-els.16'20-30 However, none of these risk factors have been prospectively validated.

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