De novo acute myeloid leukemia in the elderly; a consistent fraction of long-term survivors by standard-dose chemotherapy.

To clarify the characteristics of de novo acute myeloid leukemia (AML) among the elderly, we reviewed 112 patients over 60 years old (median age 72 years) who were treated at hospitals in Nagasaki Prefecture with a population of 1.5 million between 1987 and 1994. Reclassification of morphological diagnosis revealed that the proportion of M3 was lower but that of M6 and the incidence of cases with trilineage dysplasia (TLD), known as poor prognostic features, were higher in the elderly than in patients less than 60 years old. Similarly, chromosomal data showed a lower frequency of favorable karyotypes such as t(8;21) and t(15;17) in the elderly. The overall survival of all 112 patients was 10.3% at 5 years. Multivariate analysis indicated that good performance status (PS), low WBC at diagnosis, standard dose multi-drug chemotherapy and all-trans retinoic acid (ATRA) treatment for M3 patients, and morphological findings without TLD were significantly correlated with longer survival. Most of the long-term survivors were found among those who received standard dose therapy in this series, although no consensus has been established how to treat elderly AML patients. We propose that a prospective controlled trial is necessary to confirm the role of standard dose chemotherapy for elderly patients with de novo AML.

Jejunal perforation in a patient with adult T-cell leukemia.

We present a case of adult T-cell leukemia (ATL) with jejunal perforation at the site of intestinal involvement by ATL. A 39-year-old woman presented with sudden-onset abdominal pain. Physical examination showed generalized severe abdominal tenderness and intraabdominal free air was seen on radiographic examination. Under a diagnosis of peritonitis due to intestinal perforation, an emergency operation was performed. A pinhole-like perforation was found in the jejunum 80 cm distal to Treitz's ligament, and the patient underwent partial resection of the affected jejunum. Microscopic examination revealed diffuse infiltration of abnormal lymphocytes into the entire wall of the jejunum and mesenteric lymph nodes. A diagnosis of ATL was confirmed by the presence of antibody to human T-lymphotropic virus type 1 (HTLV-1) in the serum, a positive result for T-cell markers and the HTLV-1 proviral genome in the mononuclear cells in the specimens. The final diagnosis was thus lymphoma subtype of ATL. Combination chemotherapy was repeated until the patient died 14 months postoperatively. Emergent surgery followed by intense chemotherapy might improve survival in patients with ATL and perforated intestine.

Circulating interleukin-6 levels are elevated in adult T-cell leukaemia/lymphoma patients and correlate with adverse clinical features and survival.

We measured the circulating levels of interleukin (IL)-6 in adult T-cell leukaemia/lymphoma (ATL) patients using an enzyme-linked immunosorbent assay. The IL-6 levels in 59 ATL patients (median 8.2 pg/ml; range < 1.0 to 185.7 pg/ml) were significantly higher than in 30 healthy controls (median < 1.0 pg/ml; range < 1.0 to 3.5 pg/ml) (P < 0.0001) or 32 human T-lymphotropic virus type-I (HTLV-I) carriers (median 4.2 pg/ml: range < 1.0 to 13.3 pg/ml) (P = 0.002). Among the ATL patients, the IL-6 levels in the acute- or lymphoma-type patients were significantly higher than those in the chronic-type patients (P < 0.0001). The IL-6 levels were also higher in the patients with B symptoms than in those without B symptoms (P = 0.039), and were significantly correlated with increased serum lactate dehydrogenase (LDH) (P = 0.0004) and C-reactive protein (CRP) (P < 0.0001) and decreased serum albumin (P = 0.0003) values. The patients with elevated IL-6 levels had inferior overall survival periods compared to those with normal IL-6 levels (P = 0.025). ATL is a single disease entity, although its clinical features are quite diverse; the increased production of cytokines may cause the diversity of clinical features. The results of our study indicate that IL-6 is one such cytokine.

Integration patterns of HTLV-I provirus in relation to the clinical course of ATL: frequent clonal change at crisis from indolent disease.

We examined human T-lymphotropic virus type I (HTLV-I) DNA integration in 68 patients with adult T-cell leukemia/ lymphoma (ATL) by Southern blotting using EcoRI, which does not cut within the 9 kb of the genome and probes for pX and gag-pol region of HTLV-I. We detected defective proviral integration as a monoclonal band of various sizes with the pX but not with the gag-pol probe, or a monoclonal band of less than 9 kb with the pX probe, in 20 patients (29.4%). These were designated defective (D) type. With both probes, a single band greater than 9 kb was detected in 34 (50.0%), designated complete (C) type, and two or more bands greater than 9 kb, were designated multiple (M) type, in 14 (20.6%). Advanced age, a high LDH value, and hypercalcemia were more frequent in D type patients. The median survival time (MST) was 6.8, 24.4, and 33.3 months, for D, C, and M types, respectively (log rank P = .006). Among 52 sequentially examined patients, the HTLV-I integration patterns changed in 4 (7.5%). In three of these four, the rearrangements of the T-cell receptor (TCR)b gene concomitantly changed, suggesting the appearance of a new ATL clone. Another patient had the same rearrangement of the TCRb gene, indicating clonal evolution. The HTLV-I integration pattern changed at crisis from indolent to aggressive ATL in three patients. These findings suggested that the HTLV-I integration patterns have clinical implications in ATL pathophysiology. In contrast to the clonal evolution characteristic of the multistep carcinogenesis of most human malignancies, the frequent clonal change of ATL at crisis is a peculiar phenomenon, probably reflecting the emergence of multiple premalignant clones in viral leukemogenesis as suggested in Epstein-Barr virus associated lymphomagenesis in the immunocompromised host.

Increased levels of interleukin-6 (IL-6) in serum and spontaneous in vitro production of IL-6 by lymph node mononuclear cells of patients with angio-immunoblastic lymphadenopathy with dysproteinemia (AILD), and clinical effectiveness of cyclosporin A.

Serum levels of cytokines and in vitro cytokine production by lymph node mononuclear cells (LNMC) were studied in four patients with angio-immunoblastic lymphadenopathy with dysproteinemia (AILD) or AILD-type T cell lymphoma. An increased level of serum interleukin-6 (IL-6) was detected on initial diagnosis in both of two patients examined. Spontaneous production of IL-6 by LNMC was detected in all four patients studied. Immunosuppressive therapy with cyclosporin A (CsA) was attempted in a 68-year-old man, who was refractory to intensive combination chemotherapy. The increased level of IL-6 in this patient decreased to normal within 3 weeks of CsA administration and the patient became symptom-free. One and a half months later, the IL-6 level gradually increased along with clinical exacerbation. We also measured serum levels of IL-1 alpha, IL-2, IL-4, IFN-alpha, gamma and TNF-alpha in parallel with IL-6, but these factors were only sporadically detected. IL-6 production by LNMC was stimulated by IL-2 but inhibited by CsA. These observations suggest that IL-6 is one of the important cytokines to be involved in the pathophysiology of AILD and CsA is a useful reagent for relieving symptoms.

Plasma M-CSF as an indicator of response to chemotherapy in adult T cell leukemia patients.

The plasma concentration of macrophage colony-stimulating factor (M-CSF) was measured in 10 patients with acute type adult T cell leukemia (ATL) during the clinical course before and after chemotherapy. M-CSF concentration decreased significantly when the patients achieved complete remission (CR) or partial remission (PR) (t-test: p = 0.0001). Five of the patients showed disease progression after several months of PR, and plasma M-CSF increased at that time (t-test: p = 0.0456). Thus, plasma M-CSF concentration appeared to accurately reflect the disease activity in ATL. In support of these results, all three ATL cell lines established from these patients secreted M-CSF in vitro after stimulation with phorbol myristate acetate (PMA) or concanavalin A (Con A). Plasma M-CSF concentration, however, increased transiently when the patients were febrile (t-test: p = 0.0001), even though their ATL condition was unchanged. Taken together, these results indicate that there are two sources of increased plasma M-CSF concentration in ATL; ATL cells themselves and normal parenchymal cells that cause this increase as the result of elevated body temperature due to inflammation.

An intensive chemotherapy of adult T-cell leukemia/lymphoma: CHOP followed by etoposide, vindesine, ranimustine, and mitoxantrone with granulocyte colony-stimulating factor support.

SUMMARY: 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.

Molecular detection of pre-ATL state among healthy HTLV-1 carriers in an endemic area of Japan.

Adult T-cell leukemia/lymphoma (ATL) usually develops after age 40 in Japan, suggesting a long latency since HTLV-I is considered to be transmitted mainly from mothers to babies via breast milk. Our previous studies had suggested that HTLV-I carriers who have a monoclonal integration of HTLV-I proviral DNA in the peripheral blood cells, designated pre-ATL, account for about 2% of healthy carriers and are at high risk of developing ATL. Their ages ranged from 32 to 80 (median 57). Nevertheless, many cases of pre-ATL showed a long-lasting carrier state (10-year probability around 90%). In the present investigation we conducted a large-scale molecular detection of monoclonal integration in a population (481 cases) of healthy carriers with ages ranging from 16 to 82 (median 49) for the purpose of clarifying the earliest onset of this pre-ATL state. Southern-blot analysis of DNA extracted from peripheral blood mononuclear cells revealed 6 cases (1.2%) with a monoclonal band. All of these 6 were older than 40; no single positive case was found in 220 carriers under age 40. These results indicate that the molecularly detectable pre-ATL state also develops after a long latency. Thus the pre-ATL state seems to be a subtype of ATL showing an extremely indolent course of disease development, but not merely an early phase of all subtypes of ATL. We propose that, in order to reveal a promoter(s) responsible for the development of ATL from the pre-ATL state, intensive epidemiological investigation of life style, eating habits, occupation and exposure to carcinogens must be conducted on this unique group prone to ATL. It is also important to perform such an epidemiological study on the general population of carriers by paying special attention to the first 3-4 decades of each carrier's life in Japan and by comparing the data with those from carriers in different geographical areas of the world.

[Clinical characteristics and poor outcomes in patients with de novo AML with trilineage myelodysplasia].

De novo AML with trilineage myelodysplasia (AML/TMDS) is reported to account for 10-15% of de novo AML and respond poorly to conventional intensive chemotherapy, In our series, 12 (25%) of 48 patients with de novo AML were diagnosed as AML/TMDS. We found that the platelet count was significantly higher (p < 0.05), and the blast percentage of the bone marrow was significantly lower (p < 0.05) in the AML/TMDS group than in the AML/non-TMDS group. Sex ratio, age, WBC and RBC count did not significantly differ between the two groups. The immunological markers and the myeloperoxidase positivity of the blasts of AML/TMDS varied widely. The CR rate was 66.7% in the AML/TMDS group and 83.3% in the AML/non-TMDS group. Dysplastic changes were still detected in the bone marrow smears in 7 of 8 AML/TMDS cases who achieved complete remission. The AML/TMDS group showed significantly shorter CR duration (median; 169 days) and survival (median; 511 days, p < 0.05). However, in two cases which underwent allogeneic bone marrow transplantation (allo-BMT) during early relapse phase the disease-free survival has extended over 4 years and 2 years 8 months, respectively. Thus, we would like to propose that allo-BMT should be performed as early as possible to overcome poor outcome of AML/TMDS.

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.

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.

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.

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.

Clinical course of human T-lymphotropic virus type I carriers with molecularly detectable monoclonal proliferation of T lymphocytes: defining a low- and high-risk population.

To characterize the prodromal phase of adult T-cell leukemia (ATL), a prospective follow-up study was conducted on 50 carriers in a putative pre-ATL state. This state was defined by the presence of molecularly-detectable monoclonal proliferation of human T-lymphotropic virus type I (HTLV-I)-infected T lymphocytes, and the absence of clinical symptoms of leukemia. The median observation time was 50 months. The pre-ATL subjects were divided into two groups according to initial white blood cell (WBC) counts: group A, those with a normal WBC count (9,000/microL) (n = 30), and group B, those with an increased WBC count (9,000 to 15,000) (n = 20). Comparisons were made between the two groups and with a group of 25 patients with chronic ATL (group C) who had WBC counts of more than 15,000. Significant differences in survival rate were found between groups A and B (10-year survival 65.7%) and group C (32.8%) (P < .01), and between group A (10-year survival 90.0%) and group B (52.1%) (P < .05). The incidence of transformation to overt ATL was 10% (3 of 30) in group A and 50% (10 of 20) in group B (P < .01). In six transformed cases (one in A and five in B) we found exactly the same integration sites in pre-ATL and overt ATL phases, confirming the multistep leukemogenesis hypothesized for this disease. However, the pre-ATL subjects could be divided into two distinct prognostic groups based on the initial WBC count; those with good and those with poor prognosis. Although the 10% transformation rate (2.5% annually) in group A seemed to be extremely high compared with that in the general population of HTLV-I carriers (around 0.06% to 0.4% annually), the majority of group A subjects and some in group B showed stable clinical courses without transformation. Further, development of ATL was not observed in four group A subjects with HTLV-I-associated myelopathy (HAM), which is rarely associated with ATL. We propose to call this group of rather benign HTLV-I carriers "HTLV-I carriers with monoclonal proliferation of T lymphocytes (HCMPT)." Thus far we have been unable to identify reliable parameters other than WBC counts that prospectively distinguish HCMPT from the true pre-ATL state, in which there is a high probability of developing ATL. Further clinical and biologic approaches should elucidate the natural history of the HTLV-I carrier state and early events in ATL leukemogenesis.

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.

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.

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.

Cohort study of hepatotropic virus and human T lymphotropic virus type-I infections in an area endemic for adult T cell leukemia.

We tested for antibodies to hepatitis B virus (HBV), hepatitis C virus (HCV), and human T lymphotropic virus type-I (HTLV-I) in 629 normal inhabitants of an adult T cell leukemia (ATL) endemic area and in patients with ATL, HTLV-I associated myelopathy (HAM), and hepatocellular carcinoma (HCC) from the same district. The prevalence of serological positivity for each virus was 28.0, 6.4, and 32.6%, respectively, among the 629 inhabitants. There was a positive association between the presence of anti-HCV and serological HTLV-I positive or negative status of these subjects (9.3% vs 5.0%). Conversely, there was no correlation between HBV and HTLV-I serologic prevalence. Only inhabitants positive for anti-HCV showed significantly high serum aminotransferase levels. The levels were not affected by superimposed HTLV-I infection among anti-HCV positives. Fifty three percent of HCC patients were positive for anti-HCV; 35% of whom were simultaneously positive for antibody to HTLV-I. On the other hand, only 2 ATL patients (4.2%) and 2 HAM patients (7.7%) had anti-HCV. These findings suggest that high serum aminotransferase levels are mainly caused by HCV infection and persons with HCV and HTLV-I double infections are at a high risk for the development of HCC but not ATL or HAM.

Semiquantitative analysis of integrated genomes of human T-lymphotropic virus type I in asymptomatic virus carriers.

A semiquantitative estimation of human T-lymphotropic virus type I (HTLV-I) integration by peripheral blood mononuclear cells (PBMC) was performed. Genomic DNA samples derived from 134 HTLV-I carriers were subjected to 40 or 60 cycles of the polymerase chain reaction to amplify the pol region of HTLV-I. The HTLV-I genome was detected by dot hybridization using a 32P-labeled oligonucleotide probe for the pol region. The radioactivity of hybridized dot membranes was then counted with an RI Imaging System (Ambis Inc, San Diego, CA) and the HTLV-I genome dose was determined by comparison with standard curve for serially diluted HTLV-I genome-positive DNA. A wide range of variation of HTLV-I genome integration was observed. When the integrated genome dose was calculated as the number of HTLV-I copies per 100 PBMC, 7 carriers (5%) had more than 10 copies, 56 (42%) had 1 to 10 copies, 46 (34%) had 0.1 to 1 copy, and 24 (18%) had less than 0.1 copy. In one sample, the HTLV-I genome was undetectable, which may indicate that the integrated genome was present at less than 0.01 copies per 100 PBMC. Age- or sex-related variations in the distribution of individuals with different HTLV-I genome were rather limited. However, carriers with a high level of the HTLV-I genome were always more than 30 years old and were predominantly male (six of seven).