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We report the clinical, hematologic, and immunologic features of 18 preleukemic adult T cell leukemia (pre-ATL) cases with abnormal T lymphocytosis induced by human adult T cell leukemia-lymphoma virus (HTLV/ATLV). The patients were from the Nagasaki district, which is one of the most endemic areas of ATL in Japan. Pre-ATL is a subclinical T cell abnormality differing from ATL. It is characterized by an insidious onset and appearance of abnormal T lymphocytes (10% to 40%) in the peripheral blood without clinical symptoms except for a few cases transiently presenting fever, skin eruptions, and slight lymphadenopathies. Most abnormal T lymphocytes were small and mature with incised or lobulated nuclei and formed E rosettes with sheep RBCs. Virologic and biomolecular analysis revealed that all cases were infected with HTLV, and proviral DNA was integrated in host lymphocytes from 12 of the 14 cases examined. Furthermore, the lymphocyte populations, including abnormal T lymphocytes, were monoclonal with respect to the site of the provirus integration. Abnormal T lymphocytosis persisted from one to more than seven years in six cases, three of which developed ATL after a one- to five-year pre-ATL stage, whereas abnormal T lymphocytes spontaneously decreased in the other seven patients. However, HTLV-infected monoclonal lymphocytes were detected in four cases examined, even after most of the abnormal T lymphocytes had disappeared. Moreover, the same clonally provirus- integrated lymphocytes persisted in two of four cases not only during the course of abnormal lymphocytosis, but also in the subsequent almost- normal blood. These results indicate that the majority of the cases were in a pre-ATL state with a potential to develop ATL.

We investigated antibodies against pX gene product, p40mx, by ELISA using recombinant p40tax protein in HTLV‐I seropositive carriers as well as patients with adult T cell leukemia (ATL) and HTLV‐I‐associated myelopathy (HAM). Seventy (49.0%) out of 143 HTLV‐I healthy carriers were found to be positive for antibody against p40tax antigen and the follow‐up samples at two‐year intervals revealed constant reactivity by ELISA in each carrier. The onset of antibody production was delayed 4 to 12 weeks as compared with anti‐HTLV‐I in primary infection cases. The anti‐p40tax‐positive rate (90%) in HAM patients was significantly higher than that of healthy carriers, acute and chronic ATL patients and their family members. Furthermore, HAM patients and a few healthy carriers showed high reactivities by ELISA. Children from mothers with anti‐p40tax showed a higher anti‐HTLV‐I‐positive rate than that of children from mothers without anti‐p40tax (54.5% versus 12.5%). Two men without anti‐p40tax and one female with low anti‐p40tax developed ATL during follow‐up studies. These results suggest that HTLV‐I carriers could be divided into 2 or 3 sub‐populations according to antibody response to p40tax. A smaller population with anti‐p40tax, especially a high antibody reactivity, could have a high risk of developing HAM and of transmission from mother to child. In addition, ATL may occur in a population with low or absent anti‐p40tax.

We describe 4 cases of adult T-cell leukemia (ATL) with unusual morphology and aberrant immunophenotype. All patients were Japanese and born in the Nagasaki district, an area endemic for HTLV-I. Peripheral blood and/or bone marrow films revealed bizarre giant cells with and without large nucleoli; the cells were 5 to 6 times the diameter of erythrocytes, resembling Hodgkin's cells. Some peripheral blood cells were morphologically similar to prototypic ATL cells, while many other cells in the bone marrow showed unusual morphology. Furthermore, leukemic cells had aberrant immunophenotypes such as the CD8-positive type in patients 1 and 2, the CD4-.CD8- double-negative type in patient 3, and the CD5 antigen defect in patient 4. All patients had marked elevations of the serum calcium and LDH and organomegaly, while all had a short survival. Anti-HTLV-I antibodies and provirus DNA monoclonality were demonstrated in all patients. The results suggested that the unusual morphology and aberrant ATL cell immunophenotype may be indicative of a high grade malignant behaviour of ATL.

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