An intensive combination chemotherapy regimen supported by granulocyte colony-stimulating factor (G-CSF) was evaluated in adult T-cell leukemia/lymphoma (ATLL) patients in a multiinstitutional, cooperative study. Vincristine 1 mg/m2 i.v. day 1, Adriamycin 40 mg/m2 i.v. day 1, cyclophosphamide 400 mg/m2 i.v. day 1, prednisolone 40 mg/m2 i.v. days 1 to 3 and 8 to 10, etoposide 35 mg/m2 i.v. days 1 to 8, vindesine 2 mg/m2 i.v. day 8, ranimustine 50 mg/m2 i.v. day 8, mitoxantrone 7 mg/m2 i.v. day 8, and G-CSF 50 mg/m2 s.c. days 9 to 21 were given for 2 to 4 courses every 3 weeks to 83 patients with ATLL. Complete remission (CR) and partial remission (PR) were achieved in 35.8 and 38.3 percent, respectively, of 81 evaluable patients. The median survival of all patients was 8.5 months, with a predicted 3-year survival of 13.5 percent by the Kaplan-Meier method. The median duration of response was 7.6 months (range 0.2-42.7), and 13 patients were alive. Their median survival time was 29.1 months (range 19.2-44.7). In 67.6 percent of courses, white blood cell (WBC) nadirs were < 1.0 x 10(9)/L. Days required for the recovery of WBC from the nadir to > 1.0 x 10(9)/L were <5 days in 71.4 percent of the treatment courses. The G-CSF supported an intensified chemotherapy regimen for ATLL and yielded better response rate and longer survival compared to previous reports in Japan. Because duration of remission is still short, further studies of postremission therapy or other strategies are warranted.

Tables I and II, were the subjects of this study. The non-leukaemic patients did not show any serious disorders of haemopoiesis.The bone marrow of the patients with acute leukaemia was highly infiltrated with leukaemic cells and no specific chemotherapy had been used at the time of bone marrow puncture.The culture method used was a modification of that described by Pike and Robinson (1970). Feeder layers of peripheral white blood cells collected from normal individuals were allowed to sediment by standing at room temperature for 45-60 min. The plasma, containing white blood cells, was removed and mixed with human AB type serum obtained from a normal volunteer to a final serum concentration of 15°o together writh McCoy's 5A medium fortified with a mixture of vitamins and amino acids (Nissui Co., Tokyo). To this mixture was added liquefied 3%o agar to give' a final concentration of 0-5%. One ml aliquots containing 1 x 106 white blood cells were placed in 35 x 10 mm plastic Petri dishes (Falcon Plastics).The bone marrow cells for the upper layer w-ere obtained by sternal puncture and were washed twice with NCTC 109 solution (Difco). The red blood cells wmere removed by hypotonic lysis with distilled water for 2 min (Harris and Freireich, 1970 Japan.

The leukemic cells of 57 patients with adult T cell leukemia (ATL) were analyzed for their immunologic surface markers. Forty-four cases showed normal mature inducer/helper T cell phenotype (typical group: E-RFC+, Leu-1+, 2a-, 3a+ MASO36c-), but the other 13 cases showed unusual surface phenotypes (variant group) and could be subdivided into several groups (V1 to V5). Four cases had absent or low Leu-1 positivity (V1: E-RFC+, Leu-1-, 2a-, 3a+, MASO36c-), while two other cases with low Leu-1 positivity had both Leu-2a and 3a, a characteristic of cortical thymocytes, but were unreactive with MASO36c (V2: E-RFC+, Leu-1-, 2a+, 3a+, MASO36c-). Three cases lacked both Leu-2a and 3a despite having other T cell markers (V3: E-RFC+, Leu-1+, 2a-, 3a-, MASO36c-). The next three cases had low rosette-forming ability with sheep RBCs (V4: E-RFC-, Leu-1- approximately +, 2a- approximately +, 3a+, MASO36c-). Interestingly, one other case showed high reactivity against anti-Leu-7, which is believed to be one of the monoclonal antibodies directed against natural killer cells (V5: E-RFC+, Leu-1+, 2a-, 3a+, 7+, MASO36c-). Clinical and hematologic differences between the typical group and variant group were investigated, and it was found that the variant group (excluding V5) have statistically significant (P less than .002) higher serum lactic dehydrogenase (LDH) activity. The overall survival in the variant group was worse than in the typical group, but it was not quite statistically significant (P = .072). The median survival time was eight months for typical cases and only four months for variant cases; six cases died within two months. The V5 case was unusual not only because the patient's leukemic cells have Leu-7 antigen but also because she survived more than nine years after initial diagnosis. There seems to be some correlation between phenotypic diversity of ATL cells and prognosis.

Human T-cell leukemia virus type-1 (HTLV-1) is the established cause of adult T-cell leukemia/lymphoma. Monitoring time trends in HTLV-1 seroprevalence in blood donors is important to assess the safety of the blood supply in the viral endemic area. We analyzed changes in HTLV-1 seroprevalence in 48,415 first-time blood donors who donated blood from 2000 to 2006 in Nagasaki prefecture, an endemic area in Japan. The donors were divided into 10-year birth cohorts: before 1950, 1951-1960, 1961-1970, 1971-1980, and 1981-1990. Among the first-time blood donors, 622 were tested positive for HTLV-1 (overall seroprevalence: 1.28%, [95%CI: 1.19-1.39]). Seroprevalence was significantly high in the birth cohort of before 1950 (6.22%) and declined with birth-year. The time trend of the birth-cohort specific seroprevalence showed almost no change within each birth cohort, except for the birth cohort of 1981-1990 that showed a significantly declining trend (P for trend = 0.006). Among the birth cohort of 1981-1990, the seroprevalence was stable among those born during 1981 to 1986 (0.66-0.83%), but was lower among those born during 1987 to 1990 (0-0.38%). Detail analyses showed that HTLV-1 seroprevalence among blood donors clearly declined in those born after 1987.Keywords: HTLV-1, blood donors, seroprevalence, birth cohort analysis 3 IntroductionHuman T-cell leukemia virus type-1 (HTLV-1) is the etiological agent for adult T-cell leukemia/lymphoma (ATLL) and other HTLV-1-associated diseases [1][2][3]. The virus is transmitted through three routes: mother-to-infant, sexual contact, and blood transfusion [4][5][6][7]. In mother-to-infant transmission, breast-feeding has been reported to be the dominant route [8]. To prevent milk-borne transmission, a prefecture-wide intervention program named the ATLL Prevention Program (APP) started in August 1987 in Nagasaki prefecture, an HTLV-1 endemic area in Japan [9][10][11]. The APP involved the screening of pregnant women for HTLV-1 and the intervention to instruct the virus carrying mothers to refrain from breast-feeding. To prevent blood-borne transmission, a nationwide routine serological screening for HTLV-1 of donated blood was launched in 1986 all over Japan [4].Monitoring time trends in HTLV-1 infection rates in blood donors is important to assess the safety of the blood supply and to estimate population risks in the viral endemic area. Previous studies of Japanese blood donors reported that the age-specific HTLV-1 seroprevalence steadily declined over the decades [12][13][14][15]. Birth-cohort effects, changing the length of breast-feeding, sanitary improvement, and the dilution effect caused by HTLV-1-negative immigrants have been discussed as reasons for the declining trend [15][16][17]. Although such an age-specific analysis is commonly used for epidemiological studies, it sometimes obscures important trends that can occur within people born at different times. An alternative method of analyzing trends in viral seroprevalence is to examine birth-cohort specific tre...

Extramedullary haematopoiesis (EMH), which may occur in various types of haemodyscrasia and dyshaematopoiesis, is generally seen in the spleen, liver and lymph nodes, but rarely within the cranium. This is a case of intracranial EMH in a patient with secondary myelofibrosis which developed after the treatment of polycythaemia rubra vera.