Human T‐lymphotropic virus type 1 infection and solid organ transplantation

HTLV infection appears to be more common among renal transplant candidates than in the related general population. HTLV‐1‐associated diseases may occur in carriers who are transplanted but there is insufficient evidence to confirm whether these occur more frequently as a result of the associated immunosuppression. Consequently, pre‐existing HTLV‐1 infection should not be considered a contra‐indication to transplantation. The risk of transmission of HTLV‐1 through solid organ transplantation from a confirmed infected donor is unknown. There are anecdotes of multiple infections from a single donor. Biologically due to the significant volume of blood and the lack of storage, transmission would be expected to be higher than following blood transfusion. The rate of subsequent disease is unknown, but there are now 11 reports of HAM and 2 of ATL occurring within 4 years of transplantation associated infection. There are insufficient data to know whether the time from infection to onset of disease and the rate of progression differ from transmission through other routes, but early onset and rapid progression is a concern. Responses to enhanced immunosuppression for the treatment of HAM are variable. The risk of HTLV‐1 associated disease in exchange for a life‐saving major organ transplantation from an infected donor might be considered worth taking by some HTLV‐1 uninfected patients. Peri‐transplantation antiretroviral prophylaxis with zidovudine and raltegravir is biologically sound but therapeutically unproven. The risks related to HTLV‐1 infection appear to preclude the use of any other tissue. All transplant donors should be screened for HTLV‐1 infection regardless of perceived risk.     

Impact of p53 aberration on the progression of Adult T-cell Leukemia/Lymphoma

Based on statistical analysis of its age-dependent occurrence, a multi-step carcinogenesis model has been proposed for Adult T-cell Leukemia/Lymphoma (ATLL). We have previously reported that the deletion of the p16 gene is a key event in ATLL progression. In the current study, we report for the first time that the aberrations of p16 and p53 are mutually exclusive in ATLL and either of the two events is sufficient for the ATLL progression. More than half of the patients had one of the two aberrations, and both aberrations emerged as significant markers for a poor prognosis.     

Malignant lymphoma in Hawaii-Japanese: a retrospective morphologic survey

A retrospective morphologic survey (1973-1983) of 146 cases of malignant lymphoma among the Hawaii-Japanese (migrant Japanese and their offspring) was conducted to determine whether differences in the incidence and cytologic types of malignant lymphoma exist when compared to those of native Japanese (lifetime residents of Japan). The age-adjusted incidence rates for malignant lymphoma among the Hawaii-Japanese were similar to rates for U.S. whites. However, higher rates for follicular centre cell (FCC) lymphoma with a follicular pattern were observed in the Hawaii-Japanese population when compared with rates for native Japanese. On the basis of the cytologic types of the Lukes-Collins classification, non-Hodgkin's lymphomas among the Hawaii-Japanese resembled those of Western countries, rather than those of Japan. B-cell lymphomas predominated (72 per cent), while T-cell types comprised 23 per cent of cases. Follicular centre cell types were encountered most often (59 per cent), and the small cleaved FCC subtype was the most common (30 per cent). The high degree of follicularity (29 per cent) was at variance with the consistently low rates reported in Japan. This may be explained, in part, by higher rates of nodal lymphomas among the Hawaii-Japanese. Of the T-cell lymphomas, diffuse large cell types (T-cell immunoblastic sarcoma, T-IBS), often with cytologic pleomorphism, were relatively frequently encountered (16 per cent), and comprised 15 per cent of non-Hodgkin's lymphomas; this observation necessitates special clinical and epidemiologic consideration in view of the large Japanese migration to Hawaii from HTLV-I endemic regions of southern Japan. No registered cases of non-Hodgkin's lymphoma or of Hodgkin's disease were documented in Hawaii-Japanese subjects under the age of 15 years. The age-adjusted incidence rates for Hodgkin's disease among the Hawaii-Japanese were similar with those of native Japanese. Nodular sclerosis was the most frequent histologic subtype. The difficulty in distinguishing between Hodgkin's disease and non-Hodgkin's lymphoma, particularly when immunologic cell surface markers are not available, is addressed. Low rates for chronic lymphocytic leukemia among the Hawaii-Japanese were confirmed. Not one well-documented case was identified in the 11-year period surveyed.     

Absence of cytotoxic molecules in CD8- and/or CD56-positive adult T-cell leukaemia/lymphoma

Adult T-cell leukaemia/lymphoma (ATLL) cells usually exhibit a CD4⁺ (helper/inducer) phenotype (CD4⁺/8^–/56^–), and only a minority of tumours express the CD8 (cytotoxic/suppressor) or CD56 (natural killer [NK]-associated) antigens. TIA-1 is a cytotoxic granule-associated protein expressed in NK cells and cytotoxic T lymphocytes (CTLs). Granzyme B, perforin and Fas ligand (FasL) are also expressed in activated CTLs and NK cells. To clarify the cytotoxic potential of ATLL cells, immunohistochemistry was performed in CD8⁺ and/or CD56⁺ ATLL cells, using anti-TIA-1, anti-granzyme B, anti-perforin and anti-FasL antibodies. We studied nine cases of CD8⁺ and/or CD56+ ATLL, all of which exhibited monoclonal integration of human T-cell leukaemia virus type 1 (HTLV-1) proviral DNA. Four cases exhibited a CD8⁺/CD56^– phenotype, four others had a CD8^–/CD56⁺ phenotype, and one was CD8⁺/CD56⁺. All but one case also expressed the surface antigens CD3, TCR αβ, and CD4. Expression of granzyme B and TIA-1 were demonstrated in three and two cases, respectively, but none expressed perforin or FasL. In the control study, 10 cases with typical CD3⁺/4⁺/8^–/56^– ATLL demonstrated no expression of those cytotoxic-associated proteins. Our findings suggest that CD8 and/or CD56 positivity probably confer(s) no cytotoxic function on ATLL cells, and it is possible that CD8 and CD56 may be simply aberrant surface markers in ATLL. Received: 20 January 1999 / Accepted: 13 April 1999     

“Adult T-cell leukemia/lymphoma” with bone demineralization

Two patients with T-cell malignancy having radiographic manifestations of generalized and localized bone demineralization are reported. One, a 53-year-old man, had marked osteoporosis and severe hypercalcemia, but no clinical evidence of leukemia throughout his illness. At autopsy there was no definite evidence of bone involvement. Histologic proof was obtained from abdominal skin which revealed adult T-cell leukemia/lymphoma (ATLL). The second case, a 33-year-old man, complained of arthralgia in his hands and feet; radiographs showed severe localized demineralization and pathologic fractures. Specimens of his peripheral blood, cervical lymph nodes, and bone marrow revealed ATLL cells.