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S Atogami

Publications and source records attributed to S Atogami.

At least 37 records · Page 2Linked to original sources
PubMed1994

Significance of soluble interleukin-2 receptor levels for evaluation of the progression of adult T-cell leukemia.

BACKGROUND: The authors conducted a survey of a large cohort of patients with adult T-cell leukemia (ATL) and a group of human T-cell leukemia virus type 1 (HTLV-1) carriers to elucidate whether measurements of soluble interleukin-2 receptor (sIL-2R) levels are indicative of ATL tumor burden and correlate with clinical progression. METHODS: Using a sandwich enzyme immunoassay, the authors determined sIL-2R in the serum of 135 patients with ATL diagnosed and subclassified according to the Japan Lymphoma Study Group criteria and in the serum of healthy HTLV-1 seropositive persons. Also included were patients in the preleukemic state of ATL (pre-ATL), which is characterized by only slight blood changes but does not fit the diagnostic criteria of ATL. In the five subjects who finally advanced to overt ATL, the authors prospectively performed serial measurements of the receptor. RESULTS: Serial measurements of sIL-2R levels taken until overt ATL developed showed that these levels in the initial samples were higher than those of control subjects, even when subjects were asymptomatic or in the pre-ATL state. The serial levels of the five subjects gradually increased despite being in a clinically stable condition, finally reaching markedly high levels at the time ATL became overt. The mean sIL-2R levels of the smoldering, chronic, acute, and lymphoma subtypes of ATL were 1680 U/ml, 6680 U/ml, 45,940 U/ml, and 34,620 U/ml, respectively (P < 0.01). The sIL-2R levels of each subtype at the time of diagnosis were more correlated with tumor burden, malignant behavior, and prognosis than lactate dehydrogenase (LDH) levels. In the low, moderate, and high sIL-2R subgroups, the median survival time and percent survival probability at 2 years was 30.2 months (46.0%), 16.5 months (25.0%), and 7.7 months (15.3%), respectively. CONCLUSIONS: Serial measurements of sIL-2R levels are of clinical importance because changes of the levels correlate with disease progression, especially in early phase of ATL. The data suggest that sIL-2R may be more useful than LDH. In addition, emphasis may be placed on sIL-2R as an indicator of ATL progression status and prognosis for survival. The value of this marker in clinical practice should be confirmed prospectively.

Carrier State↗
PubMed1994

DNA aneuploidy of adult T-cell leukemia cells.

To clarify the biological characteristics of adult T-cell leukemia (ATL), immunophenotyping and DNA aneuploid analysis were performed in 72 ATL cases, using flow cytometric techniques. DNA aneuploidy was found in 45 cases (62.5%); the DNA index ranged from 1.03 to 2.16 (mean: 1.24). The incidence of aneuploidy in smoldering, chronic, acute, and lymphoma ATL subtypes was 20.0%, 46.6%, 76.3%, and 77.8%, respectively. The aneuploid patients had a greater tumor burden (adenopathy, hepatosplenomegaly, and leukocytosis with ATL cells), a higher level of serum LDH, and a higher incidence of hypercalcemia, compared with the diploid group. Further, unusual aberrant immunophenotypes were identified predominantly in the aneuploid group. Patients with aneuploidy had a 7.6 month median survival time (MST) with a 2 year survival rate of 24.6%, significantly worse than in the patients with diploidy, whose MST was 25.4 months with a 2 year survival of 60.1%. In some aneuploid patients, the disease often progresses from a static to an aggressive form. Thus, the determination of aneuploidy and unusual immunophenotype should be useful for detecting clinical behavior and for monitoring ATL patients, particularly in regard to such progression.

Adult↗
PubMed1994

Established IL-2-dependent double-negative (CD4- CD8-) TCR alpha beta/CD3+ ATL cells: induction of CD4 expression.

We established IL-2-dependent T cells from an adult T-cell leukaemia (ATL) patient whose leukaemic cells changed from CD4 single-positive in the initial phase to double-negative (CD4- CD8-) at the time of exacerbation. The cells termed SO-4 were of ATL cell origin and showed the double-negative TCR alpha beta/CD3+ T-cell phenotype. SO-4 cells acquired CD4 antigen expression following stimulation with concanavalin A (ConA) or immobilized anti-CD3 antibody. The induction was inhibited by herbimycin A, an inhibitor of protein tyrosine kinase (PTK) activity. No CD4 mRNA was detectable in unstimulated SO-4 cells but a 3.0 kb signal specific for CD4 mRNA was detected after stimulation. These findings indicate that SO-4 cells return to their original phenotype (CD4 single-positive) by stimulation involving PTK. The results indicate that there is a pathway of phenotypic cycling between CD4 single-positive and double-negative T cells.

Benzoquinones↗
PubMed1994

Increased plasma M-CSF concentration in patients with adult T cell leukemia: clinical correlation.

Plasma concentration of M-CSF was measured in 35 patients with adult T cell leukemia (ATL), using a radioimmunoassay (RIA). ATL patients showed elevated levels of plasma M-CSF concentration when compared with healthy adult volunteers. Higher M-CSF levels were observed in acute ATL patients than in patients with chronic or smouldering ATL (P < 0.0001). There was a significant positive correlation of M-CSF concentration with serum lactic dehydrogenase (LDL) level, a reliable marker for assessing the grade of malignancy in ATL (P = 0.0003). There was, however, no correlation of M-CSF concentration with total counts of peripheral blood ATL cells, neutrophils or monocytes, or with serum calcium levels. Although there was a significant positive correlation of M-CSF concentration with body temperature (P = 0.003), there was not a significant correlation of M-CSF concentration with C-reactive protein (CRP), a protein indicative of the severity of inflammation (P = 0.063). These results indicate that plasma M-CSF concentration reflects the disease activity of ATL, and can thus serve as a marker in the clinical subclassification of ATL patients.

Adult↗
PubMed1994

Morphological and immunophenotypical characterization of Japanese B-cell lymphocytic leukemia.

We have analyzed the clinical and laboratory features of 42 patients with B-cell leukemia. Based on the FAB criteria, the cases were classified in 3 groups: I) typical CLL 15, II) atypical CLL 9 which included 6 cases with large cells, and III) B-cell lymphoma in leukemic phase 18. Cases diagnosed as typical CLL (group I) had similar features to those seen in CLL patients from Western countries. The morphology and markers in cases from group III corresponded to B-cell lymphoma in leukemic phase. On the other hand, group II included 3 cases classified as atypical CLL according to FAB criteria. 1 CLL/PL and 2 mixed CLL and 6 cases with rather distinct features, namely: 1) lymphocytosis (42 +/- 41 x 10(9)/l in average) with large mature-looking lymphocytes with abundant cytoplasm: 2) an immunological profile consistent with CLL but, in addition with the consistent expression of CD38; 3) absence of a monoclonal band in the serum and 4) a clinical course and prognosis similar to CLL. Our findings suggest the existence of a B-cell disorder in Japan very close to CLL but distinct from typical and atypical CLL as seen in Western countries. Further studies would clarify whether such an entity is exclusively confined to Japan having a distinct natural history.

Adult↗
PubMed1994

Human T-lymphotropic virus type-I influence on hepatotropic virus infections and the subsequent development of hepatocellular carcinoma.

We studied the serologic status, with respect to hepatitis B virus (HBV), hepatitis C virus (HCV), and human T-lymphotropic virus type-I (HTLV-I) of blood donors in an area endemic for adult T-cell leukemia (ATL). Similarly, we studied the serologic status of hepatocellular carcinoma (HCC) patients from the same district. In the donors, the incidence of serological positivity for these viruses was 0.95, 1.23, and 3.75%, respectively. There was a positive correlation between the presence of anti-HCV and serological HTLV-I positive status in these subjects (1.9 vs. 1.1%) for those with HTLV-I negative status, implying high susceptibility for HCV infection among HTLV-I carriers. Fifty-nine percent of HCC patients were positive for anti-HCV and twenty-six percent of those were simultaneously positive for the antibody to HTLV-I. HCC patients infected with HTLV-I were younger than patients not so infected (61.5 +/- 8.8 vs. 64.8 +/- 8.4 years, p < 0.05). These observations suggest the possibility that HTLV-I could be one of the factors that promote the development of HCC caused by hepatotropic viruses.

Adolescent↗
PubMed1993

Characteristics of chemotherapy-induced clinical remission in long survivors with aggressive adult T-cell leukemia/lymphoma.

The acute and lymphoma types of adult T-cell leukemia/lymphoma (ATL) usually have a very poor prognosis, although some patients achieve long survival after chemotherapy. A total of 114 patients with these aggressive types of ATL were newly diagnosed at our institution from 1975 to 1989. By multivariate analysis, poor performance status and high serum creatine levels were associated with shortened survival. With combination chemotherapy, 20 patients achieved complete remission (CR), 53 achieved partial remission (PR) and 35 showed no response. Fifteen of the CR or PR patients survived for more than two years and all other patients survived for less than two years. As compared with short survivors (< 2 years) after remission, long survivors (> or = 2 years) after remission had a higher CR/PR ratio, a longer time until remission and a higher doxorubicin dose to achieve remission. Death due to causes other than the primary disease occurred in 18% of short survivors after remission and in 11.2% of nonresponders, but in none of the long survivors. Long survivors with acute ATL included 6 patients with CR and 5 patients with PR. All four lymphoma type ATL long survivors achieved CR. Monoclonal integration of HTLV-I provirus was detected in the peripheral blood mononuclear cells of all 3 PR long survivors with acute ATL studied, but was not detected in all 4 CR cases studied at remission. The minimum CD4/CD8 ratio of peripheral mononuclear cells at remission was < 1.0 in all acute ATL long survivors with CR, and was > 1.0 in all acute ATL long survivors with PR. Three out of six acute ATL long survivors with CR developed suspected viral infection just before achieving CR. Our findings show that in aggressive ATL the characteristics of remission are heterogeneous even among long survivors.

Adult↗
PubMed1993

Unusual morphological features of adult T-cell leukemia cells with aberrant immunophenotype.

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.

Aged↗
PubMed1992

Frequency of eosinophilia in adult T-cell leukemia/lymphoma.

Cases of adult T-cell leukemia/lymphoma (ATLL) display several peculiar clinical features, including skin rash, hypercalcemia, and an increase in the absolute neutrophil count. The patients rarely have pronounced eosinophilia. In this study, the eosinophilia observed in lymphoproliferative disorders of 62 patients with ATLL, 27 with T-cell lymphoma (TL), and 19 with B-cell lymphoma (BL) was investigated. The incidence of eosinophilia (greater than or equal to 570/microliters) was higher in patients with ATLL than in patients with TL or BL. Thirteen patients with ATLL (21.0%), 3 with TL (11.1%), and 2 with BL (10.5%) had eosinophilia. Of these patients, three with ATLL and one with TL who had a pathologic diagnosis of immunoblastic lymphadenopathy (IBL) showed pronounced eosinophilia up to 10,934/microliters. Because the number of eosinophils in the peripheral blood of these patients correlated both with the number of ATLL cells and the degree of lymphadenopathy and because this fluctuated with chemotherapy, it seems likely that the secretion of some lymphokines by the lymphoma cells is responsible for the eosinophilia.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Phenotypic diversity and prognosis of adult T-cell leukemia.

We examined phenotypically 107 patients with adult T-cell leukemia (ATL), using a panel of monoclonal antibodies, in order to clarify the occurrence of aberrant phenotypes, and to determine the correlation between phenotypic diversity and prognosis. The incidence of the typical (CD4+.CD8-) phenotype, the double-negative (CD4-.CD8-), the double-positive (CD4+.CD8+), and the CD8-positive (CD4-.CD8+) phenotypes was 81%, 7%, 7%, and 4%, respectively. The median survival time (MST) for all patients was 10.0 months with 17% survival at 2 years. The patients with typical phenotypes had a 10.2 month MST with 20% survival at 2 years, significantly better than the patients with the unusual phenotypes whose MST were 4.9, 7.8, and 2.6 months, respectively, for the double-negative, double-positive, and CD8-positive phenotypes. Lack of antigens reactive with CD2, CD3, CD5, and WT31 monoclonal antibody panels was one factor in bad prognosis, but the presence of CD4 and CD8 antigen abnormalities was much more significant.

Antigens, CD↗
PubMed1992

Remission with morphological myelodysplasia in de novo acute myeloid leukaemia: implications for early relapse.

Myelodysplastic features of remission bone marrow were investigated in 46 adults with de novo acute myeloid leukaemia (AML) according to the FAB morphological criteria for myelodysplastic syndromes (MDS). Compared with a group of 18 patients with the common type of acute lymphoblastic leukaemia in remission, micromegakaryocytes (30.4% v. 5.6%, P less than 0.05), multi-separated nuclear megakaryocytes (45.7% v. 0%, P less than 0.01), degranulated neutrophils (39.1% v. 5.6%, P less than 0.05), and neutrophils with hyposegmented nuclei (34.8% v. 0%, P less than 0.01) were significantly more common in the AML patients. In contrast, dyserythropoietic changes had a similar incidence in both groups. When compared with the clinical features at initial diagnosis in AML cases, the dysmegakaryocytic changes in remission marrow were found to be significantly more frequent in patients with monocytic involvement (mainly M4) or trilineage myelodysplasia (T-MDS AML). Disease-free survival was significantly shorter in patients with micromegakaryocytes (P less than 0.05) or neutrophils with hypogsegmented nuclei (P less than 0.05) than in those without these features. Overall survival was also significantly shorter in patients with micromegakaryocytes (P less than 0.05). These findings may help in developing new strategies for the post-remission therapy of AML, and also suggest that myelodysplastic changes in the remission marrow of de novo AML patients may be related to haematopoietic recovery by a preleukaemic clone which eventually leads to early leukaemic relapse. Dysplastic marrow, however, was not necessarily associated with peripheral pancytopenia in the present series, warranting basic research on such putative clonal remissions.

Acute Disease↗
PubMed1991

Prognostic significance of the proportion of Ki-67-positive cells in adult T-cell leukemia.

The authors examined peripheral blood samples from patients with adult T-cell leukemia (ATL) using the monoclonal antibody Ki-67 which detects a nuclear antigen present in actively proliferating cells. In patients with chronic ATL, the percentage of Ki-67-positive cells was significantly lower than in acute ATL patients (median values, 3.3% versus 18.9%, P less than 0.001). Furthermore, there was a significant inverse correlation between the percentage of Ki-67-positive cells and the length of survival (P less than 0.001). Serum lactic dehydrogenase (LDH) levels also showed a significant inverse correlation with survival, but this was less strong than that for Ki-67 (0.01 less than P less than 0.02). Thus, Ki-67 positivity appears to indicate the aggressiveness of ATL, and can possibly be used for the clinical classification of ATL patients as well as for the prediction of prognosis.

Antigens, Neoplasm↗
PubMed1991

[Infection prophylaxis in patients with hematological malignancies (II)--Successful prophylaxis of tuberculosis with isoniazid].

In a retrospective study to evaluate the efficacy of isoniazid (INH) for the prevention of tuberculosis, we studied 1760 patients with hematological malignancies over a twenty-year period (1970-1989). 759 patients received oral INH, most of all received 400 mg per day. Only one (0.1%) of the patients receiving INH developed tuberculosis, whereas nine (0.9%) of the 1001 patients who did not receive INH developed tuberculosis (p less than 0.05). We found that INH was very effective in the prevention of tuberculosis in patients with hematological malignancies, and was well tolerated.

Adolescent↗
PubMed1990

[Treatment of acute lymphoblastic leukemia in adults by the modified protocol of L-10M (Sloan-Kettering)].

We have treated 20 adult patients with acute lymphoblastic leukemia (ALL) and 2 patients with lymphoblastic lymphoma with a protocol modified from L-10M of the Memorial Sloan Kettering Cancer Center. Eighteen patients (81.8%) entered complete remission (CR). Eight of them eventually relapsed (only 1 patient had a meningeal relapse) and died. Median CR duration was 19 months (median overall follow-up of 35 months and 50% remission duration was not yet determined. Median overall survival was 19 months. Three patients died of sepsis during remission induction, but all of other deaths were due to resistant or relapsed leukemia. The four patients who completed 3.5 year's modified L-10M protocol were free from relapse for 6-11 months (mean 8.7). Although further follow-up is necessary, we suggest that modified L-10M protocol is effective for adult ALL and long-term survival may be available.

Adolescent↗
PubMed1990

[Infection prophylaxis in patients with hematological malignancies (I)--Successful prophylaxis of Pneumocystis carinii pneumonitis with sulfamethoxazole-trimethoprim].

In a retrospective study to evaluate the efficacy of sulfamethoxazole-trimethoprim (SMX-TMP) for the prevention of Pneumocystis carinii pneumonitis, we studied 1760 patients wit hematological malignancies over a twenty-year period (1970-1989). 449 patients received oral SMX-TMP, most of all received 400 mg of SMX and 80 mg of TMP twice per day. None of the patients receiving SMX-TMP developed P carinii pneumonitis, whereas twenty-six (2.0%) of the 1311 patients who did not receive SMX-TMP developed P carinii pneumonitis (p less than 0.01). We found that the SMX-TMP was very effective in the prevention of P carinii pneumonitis in patients with hematological malignancies, and was well tolerated.

Administration, Oral↗
PubMed1989

[A trial for prolongation of chronic phase of chronic myeloid leukemia--maintenance of leukocyte counts within normal range with busulfan].

To prolong the survival of patients with chronic myeloid leukemia (CML), 19 patients were treated with busulfan to keep their leukocyte counts within normal range by controlling bone marrow hyperplasia. The duration of chronic phase in these patients was significantly longer than that in historical controls who were treated conventionally with busulfan. This prolongation was not ascribable to the difference in such prognostic factors between the two therapy groups as splenomegaly, leukocyte count and percentage of peripheral blasts. There was a significant difference again in the duration of chronic phase between the two therapy group even when restricted to each 11 patients with intermediate relative risk (0.7-1.5) according to Sokal et al. Four patients showed thrombocytopenia less than 5 x 10(4)/microliters, but all these patients recovered within 4 months and there was no further critical side effect except subcutaneous bleeding. This study suggests that maintenance of leukocyte count within normal range and suppression of granuloid hyperplasia in bone marrow with busulfan may prolong chronic phase of CML. Probability of clonal evolution may be decreased by reducing the total leukemic cell mass and suppressing cellular turnover of primitive CML stem cells. Another possibility is that prolongation of chronic phase might be dependent on the appearance of normal karyotype clone after long-term bone marrow suppression just like after intensive chemotherapy or alpha-interferon therapy.

Adolescent↗