Indirect immunofluorescence of certain human sera demonstrated an antigen(s) in the cytoplasm of 1-5% of the cells of a T-cell line, MT-1, from a patient with adult T-cell leukemia (ATh), which is endemic in southwestern Japan. The antigen was not detected in other human lymphoid cell lines, including six T-cell lines, seven B-cell lines, and four non-T non-B cell lines. The antigen did not show cross antigenicity with that of herpesviruses, including Epstein-Barr virus, herpes simplex virus, cytomegalovirus, varicella-zoster virus, herpesvirus saimiri, and Marek disease virus. The proportion of antigen-bearing cells was increased by a factor of =5 on culture in the presence of 5-iodo-2'-deoxyuridine. Antibodies against the antigen in MT-I cells were found in all 44 patients with ATL examined and in 32 of 40 patients with malignant T-cell lymphomas (most of them had diseases similar to ATL except that leukemic cells were not found in the peripheral blood). The antibodies were also detected in 26% of the healthy adults examined from ATL-endemic areas but in only a few of those examined from ATL-non-endemic areas. On electron microscopy, extracellular type C virus particles were detected in pelleted MT-I cells cultured in the presence of5-iodo-2'-deoxyuridine. Recently, a probably new disease entity, adult T-cell leukemia (ATL), was proposed by Takatsuki and his co-workers (1, 2). Since then, many patients having ATL have been reported. These patients have been reported from a restricted area of southwestern Japan (3-7). This malignant disease has also been called adult T-cell leukemia/lymphoma (ATLL) because of its leukemic lymphoma nature. Its characteristic clinical and hematological features are: (i) onset in adulthood; (ii) acute or chronic leukemia with rapid progression; (iii) resistance to treatment with current antileukemic agents; (iv) appearance in peripheral blood of pleomorphic leukemic cells that have markedly deformed nuclei and T-cell surface markers; (v) frequent accompaniment by lymphadenopathy, hepatosplenomegaly, and hypercalcemia; (vi) absence of mediastinal tumor; and (vii) frequent skin lesions such as erythroderma and nodule formation (1)(2)(3)(4)(5)8).While studying the viral etiology ofthis malignancy, we found an antigen associated with a long-term cultured ATL cell line that is reactive with the sera of all the ATL patients tested and also with the sera of >25% ofhealthy adults from ATL-endemic areas but not with sera from those from nonendemic areas. We also detected type C virus particles in this cell line by electron microscopy.MATERIALS AND METHODS Cells. The MT-1 cell line derived from the peripheral blood of a patient having ATL (9) Sera. Sera was obtained from adult patients who have ATL or various other diseases and from healthy adults from both ATL-endemic and ATL-non-endemic areas (Fig. 1) The publication costs ofthis article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734...

Background. Lethal midline granuloma is now considered to be a malignant lymphoma derived from peripheral T cells or from natural killer cells. The therapeutic outcome of nasal T‐cell lymphoma (NL) treated by conventional chemotherapy for non‐Hodgkin's lymphoma is poor, although some patients have a good response to radiotherapy. To clarify the mechanisms of drug resistance, the expression of P‐glycoprotein (P‐gp)/MDR1, which is the product of the multidrug resistance (MDR) 1 gene, and MDR3 mRNA in NL cells, were examined. Methods. Ten Japanese patients with NL were studied. Nine of these patients were examined before therapy. P‐glycoprotein expression and phenotypes of lymphoma cells were examined by immunohistochemical staining using UIC2 as an anti–P‐gp monoclonal antibody. In one case, the Rhodamine‐123 efflux test was performed. MDR1 and MDR3 mRNA were detected by reverse transcription polymerase chain reaction. Results. Nine of the 10 patients were P‐gp positive. In one of nine, functional P‐gp expression was observed. MDR1 mRNA was detected in all seven examined patients with P‐gp positive NLs, whereas MDR3 mRNA was negative. Retrospectively, patients who received chemotherapy alone had poorer outcome than those treated by combination chemotherapy after irradiation. Conclusion. The poor prognosis for patients with NL treated with chemotherapy may be explained by P‐gp expression of the NL cells. Cancer 1995; 76:2351–6.

Background. Although colony-stimulating factors have been shown to accelerate recovery from severe neutropenia after intensive chemotherapy or bone marrow transplantation, their use in acute leukemia has been controversial because in vitro they stimulate leukemic colonies as well as normal granulocyte colonies. Methods. We conducted a prospective, randomized, controlled study to determine the safety and efficacy of recombinant human granulocyte colony-stimulating factor (CSF) after a standard course of intensive therapy in 108 patients with relapsed or refractory acute leukemia (67 with acute myelogenous leukemia, 30 with acute lymphocytic leukemia, 9 in blast crisis from chronic myelogenous leukemia, and 2 with acute leukemia arising from myelodysplastic syndromes). Treatment with granulocyte CSF (200 micrograms per square meter of body-surface area per day in a 30-minute infusion) was begun two days after the end of the chemotherapy and continued until the neutrophil count rose above 1500 per cubic millimeter. Results. Treatment with granulocyte CSF accelerated the recovery of neutrophils significantly (P less than 0.01), shortening it by about a week, but it had no effect on platelet recovery. Although the incidence of febrile episodes was almost the same, documented infections were significantly less frequent in the group treated with granulocyte CSF (P = 0.028). There was no evidence that granulocyte CSF accelerated the regrowth of leukemic cells. Fifty percent of 48 patients in the CSF group who could be evaluated and 36 percent of 50 controls had complete remission. The rate of relapse was almost the same in the two groups. Conclusions. It appears that recombinant human granulocyte CSF is safe in acute leukemia, accelerating neutrophil recovery and thereby reducing the incidence of documented infection without affecting the regrowth of leukemic cells. It should be used with caution, however, pending further confirmation of these early results.

Summary. To investigate the efficacy and safety of granulocyte colony‐stimulating factor (G‐CSF) in patients with acute myelogenous leukaemia, a multicentre randomized study was performed. From October 1993 to September 1996, 270 patients with newly diagnosed acute myelogenous leukaemia were randomized to G‐CSF or control groups after remission induction therapy. The G‐CSF group received G‐CSF (Filgrastim) from 48 h after the completing chemotherapy until the absolute neutrophil count exceeded 1·5 × 109/l. The control group did not receive G‐CSF unless severe infection occurred. There were 245 evaluable patients (120 and 125 in the G‐CSF and control groups respectively). The complete remission rate was similar in the G‐CSF and control groups (80·8% versus 76·8%), as was the 5‐year probability of disease‐free survival (34·5% versus 33·6%) and overall survival (42·7% versus 35·6%). Neutrophil recovery was significantly faster in the G‐CSF group than in the control group (12 d versus 18 d, P = 0·0001). The median duration of febrile neutropenia was significantly shorter in the G‐CSF group than in the control group (3 d versus 4 d, P = 0·0001). In conclusion, prophylactic administration of G‐CSF after remission induction therapy for acute myelogenous leukaemia is safe and useful even in patients without infection on completing chemotherapy.

Background. It was assessed whether addition of vincristine (VCR) to remission induction therapy would increase the complete remission (CR) rate, and, secondarily, whether 12 courses of maintenance—intensification therapy would produce longer survival than 4 courses in adult acute myeloid leukemia (AML). Methods. A randomized comparison of individualized induction therapy was conducted between daunorubicin, behenoyl cytarabine, 6‐mercaptopurine, and prednisolone with or without VCR. After 3 courses of intensive consolidation therapy, maintenance—intensification therapy was randomized to 4 or 12 courses given every 6 weeks. Results. Of 265 patients registered, 252 were evaluable. CR was obtained in 78%; 80% in 205 patients of age younger than 60 years, and 65% in 47 of age 60 years or older. Addition of VCR reduced the CR rate significantly (84% to 70%, P = 0.007). Predicted 4‐year survival, continuing CR, and disease‐free survival (DFS) rates of 196 CR patients are 45%, 41%, and 35%, respectively. Patients receiving 12 courses of maintenance—intensification showed better DFS. By multivariate analyses, significant factors for achievement of CR were performance status 0 to 2, age younger than 60 years, and no VCR; and those for longer DFS were achievement of CR by one course, age younger than 50 years, and French—American—British (FAB) classification M3 or M5. Among 131 patients randomized to the maintenance, the administration of 12 courses was the most important factor (P = 0.0040) for longer DFS, followed by FAB M3 or M5, and by achievement of CR by one course. Conclusions. Addition of VCR in remission induction therapy was harmful, and longer intensive maintenance therapy prolonged DFS in adult AML.