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OBJECTIVES: We describe a rare case of adult T-cell leukemia (ATL) presenting with dry mouth and swelling of bilateral parotid and submandibular glands. The unusual involvement of these exocrine glands by malignant cells prompted us to conduct a detail characterization of these infiltrating and circulating leukemic T cells, which may provide insight to the pathogenesis of exocrine involvement in ATL. METHODS: Immunophenotyping of peripheral ATL cells and microscopic examinations of various organs prepared by autopsy were performed. Analysis of the repertoire of T-cell receptor (TCR) of parotid gland-infiltrating ATL cells using molecular and immunohistochemical examinations were also performed. RESULTS: Microscopic examinations of various organs prepared by autopsy revealed the predominant and specific exocrine gland infiltration of ATL cells. Reverse transcription-polymerase chain reaction (RT-PCR) followed by both TCR spectratyping and complementary determining region (CDR)-3 sequencing analysis of TCR Vbeta of parotid gland-infiltrating T cells revealed a relatively restricted but not single usage of TCR Vbeta. Immunohistochemical analyses of parotid gland specimens detected only a small number of TCR Valphabeta-positive cells in parotid gland-infiltrating ATL cells. CONCLUSIONS: The predominant infiltration of ATL cells in exocrine glands implied that these T cells recognized exocrine gland-specific antigen. However, the absence of both TCR Vbeta mRNA transcripts and TCR Valphabeta protein expression in most ATL cells suggested that antigen recognition via TCR may not have played a major role in adhesion and subsequent infiltration into the exocrine glands in this patient. These results provide important background information to further elucidate the pathogenesis of exocrine gland-specific inflammation.

Adenovirus (AdV) infection is an important cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. We treated 16 patients with AdV hemorrhagic cystitis (HC) following HSCT with cidofovir (CDV; 1 mg/kg/day, three times weekly for 3 weeks). Patients included 10 males and six females with a median age of 50 years (range 10-62). Two of the 16 patients were unevaluable because of early death from nonadenoviral causes. CDV therapy cleared AdV from urine in 12 of 14 patients (86%). Of 14 patients, 10 (71%) showed clinical improvements in HC. Among 14 patients, seven (50%) had avoided renal damage, the most important CDV toxicity. One patient previously treated with foscarnet for cytomegalovirus (CMV) required hemodialysis, and CDV treatment was discontinued. In another patient, CDV treatment was discontinued because of grade 2 nephrotoxicity. Four patients became positive for CMV antigenemia while being treated with CDV, and two developed herpes simplex virus (HSV) stomatitis while being treated with CDV. CDV proved effective in treating AdV HC in transplant patients. However, CDV at 1 mg/kg/day given three times weekly failed to prevent breakthrough infection with CMV and HSV in some patients.

[Introduction] Natural killer (NK) cells show cytotoxicity against virus-infected cells and some tumor cells. The highly polymorphic killer cell immunoglobulin-like receptors (KIRs) which recognize HLA class 1 molecules play a major role in these cytotoxic activities, and also express on some T-cells. Human T-lymphotrophic virus-1 (HTLV-1) is a caucassive agent for leukemia and some autoimmune diseases. We investigated the correlations between the KIR genotype and susceptibilities to HTLV-1 associated diseases i.e. adult T-cell leukemia (ATL) and HTLV-1 associated myelopathy (HAM). [Materials and Methods] Fifty six HTLV-1 carriers, fifty one ATL patients and fifty seven HAM patients were recruited in this study. Genotyping of six KIR genes (3DL1, 2DL5, 2DS1, 2DS2, 2DS3 and 3DS1) was performed using PCR amplification with sequence specific primers (Martin et al. J Immunol 2002). [Results and Conclusion] Frequencies of each KIR and genotype were analysed as described in Table. Genotype means the pattern of positive KIR combinations. Significant differences between carrier vs. HAM in genotype 2 (p=0.01), and ATL vs. HAM in genotype 4 (p=0.01) were observed. Increased frequencies of genotype 3 and 2DS3 allele in HAM compared to carrier were also observed although these tendencies were not statistically significant. These preliminary results suggest that KIR gene polymorphism may play a role in determining susceptibility to HTLV-1 associated diseases. KIR genetype and HTLV-1 associated diseases Genotype 3DL1 / 2DL5 2DS1 / 2DS2 2DS3 / 3DS1 Carrier (%) * ATL (%) * HAM (%) * * this measns the genotype frequency; Y, positive; N, negative 1 Y / N N / N N / N 51.8 47.1 63.2 2 Y / Y Y / N N / Y 26.8 21.6 8.8 3 Y / Y Y / N Y / Y 1.8 7.8 10.5 4 Y / N N / Y N / N 5.4 11.8 0 5 Y / Y N / Y Y / N 1.8 2.0 7.0 6 N / Y Y / N N / Y 1.8 2.0 3.5 7 Y / Y Y / Y N / Y 1.8 3.9 1.8 Others 8.9 3.9 3.5 Carrier (%) 96.5 / 42.9 39.3 / 16.1 10.7 / 35.7 ATL (%) 96.1 / 41.2 39.2 / 21.6 9.8 / 39.2 HAM (%) 94.7 / 36.8 29.8 / 14.0 22.8 / 28.1

In June 1994, a 39 year-old male with adult T-cell leukemia was admitted to our hospital and received combination chemotherapy including epipodophyllotoxin for approximately 1 year. The monocyte count increased gradually beginning in April 1995, accelerating to 100 × 10 9 /l in January 1996, when he was diagnosed with acute monocytic leukemia. Inv(11)(q21;q23) × 2 was recognized at that time by chromosome analysis, and rearrangement of the MLL gene was shown by Southern blot analysis. From the clinical course and subsequent examinations, the case was regarded as epipodophyllotoxin-related secondary leukemia. Recently, epipodophyllotoxin has frequently been used as a treatment agent for adult T-cell leukemia. It is valuable to note that secondary leukemia may follow even such an aggressive leukemia as adult T-cell leukemia.