Adult T cell leukemia with atypical surface phenotypes: clinical correlation.

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.

Exaggerated messenger RNA expression of inflammatory cytokines in human T-cell lymphotropic virus type I-associated myelopathy.

OBJECTIVE: To investigate the expression of inflammatory cytokine messenger RNA (mRNA) in peripheral blood mononuclear cells of patients with human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM). PATIENTS: Seventeen patients with HAM, 18 HTLV-I-seropositive carriers, and 10 seronegative individuals were studied. MAIN OUTCOME MEASURE: We compared the expression of tumor necrosis factor alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon alpha (IFN-alpha), IFN-beta, and IFN-gamma, and interleukin 1 alpha (IL-1 alpha) and IL-1 beta by reverse transcriptase-polymerase chain reaction. RESULTS: In patients with HAM, the reverse transcriptase-polymerase chain reaction products of TNF-alpha, GM-CSF, IFN-gamma, and IL-1 alpha were detected in significantly higher incidences than in HTLV-I-seropositive carriers and seronegative controls. Furthermore, simultaneous mRNA expression of three or more of these four cytokines was detected in all patients with HAM compared with only 21.4% of HTLV-I-seropositive carriers. By contrast, there was no significant difference in mRNA expression of IFN-alpha, IFN-beta, and IL-1 beta among patients with HAM, HTLV-I-seropositive carriers, and HTLV-I-seronegative controls. CONCLUSIONS: An exaggerated mRNA expression of several inflammatory cytokines, including TNF-alpha, GM-CSF, IFN-gamma, and IL-1 alpha, was demonstrated in peripheral blood mononuclear cells of patients with HAM. Moreover, transcripts of these cytokines were simultaneously up-regulated in patients with HAM, suggesting that an inflammatory state in the central nervous system may be related to the pathogenesis of HAM.

Monoclonal integration of HTLV-1 in pleural effusion cells in a seropositive patient with tuberculous pleuritis.

The pleural effusion of a 79-year-old man who was a carrier of human T-cell leukemia virus type 1 (HTLV-1) showed monoclonal growth of HTLV-1 infected T-cells. While the integration pattern of HTLV-1 was polyclonal in the peripheral blood mononuclear cells, it was monoclonal in the infiltrated cells of the pleural effusion. Morphologically atypical lymphoid cells were also found in the peripheral blood and in the pleural effusion. The pleural effusion disappeared after treatment with antituberculous drugs. The nature of the monoclonal proliferation of HTLV-1 infected T-lymphocytes is discussed.

Case report: intracranial extramedullary haematopoiesis in postpolycythemic myelofibrosis.

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.

Reinfusion of autogenous ascitic fluid concentrated by freezing in patients with intractable ascites.

Eleven patients with intractable ascites were treated by intravenous reinfusion of concentrated autogenous ascitic fluid. The ascitic fluid was drained and centrifuged for removal of cells by a cell separator. Cell-free ascitic fluid was frozen in a medical freezer at -15 degrees C and thawed at room temperature. The fraction at the initial stage of melting contains a high concentration of protein and was thus collected and reinfused to the patient. In this initial fraction, the recovery rate of albumin was 42.0 +/- 9.0% and the concentration of protein was 7.1 +/- 2.4 g/dl. This frozen method is inexpensive and time saving, because it does not use a filter. Ascites was ameliorated in all patients with 1 to 19 times of reinfusion. Therefore, when renal function is not disturbed, the frozen method may be indicated for management of intractable ascites.

Decline in the positive rate of human T-lymphotropic virus type-1 (HTLV-1) antibodies among blood donors in Nagasaki.

OBJECTIVE: The aim of this study was to clarify the trend of the HTLV-1 seroprevalence rate among blood donors. METHODS: Samples were screened by the particle agglutination test for HTLV-1 antibodies. MATERIALS: Serum from blood donors was screened. RESULTS: The positive rate of HTLV-1 antibodies among blood donors decreased from 13.14 to 0.81 % over the years from 1928 to 1983. CONCLUSION: A decline over the years in the positive rate of HTLV-1 antibodies among blood donors was revealed.

[Serum iron in blood donors].

We accept blood donations from many people daily. It is important to clarify levels of serum iron (SI) in blood donors. We measured SI in 62,054 blood donors (37,989 male and 24,065 female) between 16 and 64 years of age. SI was 108.2 +/- 39.5 micrograms/dl in males and 88.5 +/- 35.7 micrograms/dl in female. SI did not differ significantly with age in females, although it is slightly lower in women aged < or = 19 than in women aged < or = 20 years. In men, SI decreased with age from 20 to 64 years old, although the course of the decrease is not clear. These data should be of use to blood programme.

[Reinfusion of concentrated autogenous ascitic fluid in a patient with selective IgA deficiency].

A 47 year-old man with selective IgA deficiency (SIgAD) consulted us in November 1981, with complaints of leg edema and common cold-like symptoms and was diagnosed as SIgAD based on data of his serum protein (IgG 2,160 mg/dl, IgM 65 mg/dl, no detectable IgA). Later in July 1989, he was admitted with edema and ascites. Laboratory examinations showed; total protein 4.6 g/dl, albumin 1.26 g/dl, IgG 2,375 mg/dl, IgM 38 mg/dl, no detectable IgA. C3 22 mg/dl, C4 6 mg/dl, antinuclear antibody 80X, anti dsDNA antibody 4.5 U/ml, anti IgA antibody 258%, and lymphocytopenia. Co-culture of lymphocytes from the patient and normal subject revealed deficiency of IgA synthesis in his B cell populations. Systemic lupus erythematosus was suggested based on the findings of skin biopsy, renal damage, oral ulcer, decreased complements, autoantibody and lymphocytopenia. We could not give him conventional products of albumin and frozen plasma because he had anti IgA antibody. Instead, we administered concentrated autogenous ascitic fluid and prednisolone. His ascitic fluid disappeared and complements and albumin in his serum normalized. He has continued in good condition and is being treated as an outpatient.

[Adult T-cell leukemia (chronic type) with unusual surface phenotype CD 4+5+8-, Leu 7+ at acute crisis].

Chronic adult T-cell leukemia with surface phenotype CD 4+5+8-, Leu 7+ at acute crisis was presented. A 43-year-old female visited our hospital complaining of generalized lymphadenopathy and skin rash in December, 1973. Peripheral blood picture and histological findings of skin led to the diagnosis of malignant lymphoma (leukemic type). Intermittent chemotherapy kept white blood cell count less than 25,000/microliters for more than 9 years. In January, 1983, abnormal lymphocytes began to increase and reached 100,000/microliters or over in a few months. Surface marker study showed their phenotype as CD 4+5+8-, Leu 7+ and anti-ATLA antibody was positive in the patient, her son and her daughter. Intensive chemotherapy was ineffective and she died in August, 1983. Histological diagnosis of lymph-nodes on autopsy was malignant lymphoma (diffuse, small cell type). This case is considered unusual in both clinical course and surface phenotype of its leukemic cells.

[Temporary spontaneous remission in Ki-1 (CD30) lymphoma with gastric lesion].

A case of 56 year-old man with Ki-1 (CD30) lymphoma is reported. He noticed cervical lymph node swelling and was admitted with temporary diagnosis of gastric adenocarcinoma in February 1986. His physical examination showed several from 1 to 4 cm size enlarged cervical and axillary lymph nodes. His first lymph node biopsy demonstrated the histological picture of malignant lymphoma. After 20 days his second lymph node biopsy demonstrated the picture of necrosis. Second gastric biopsy showed the picture of neither gastric cancer nor malignant lymphoma, in spite of his first gastric biopsy finding with adenocarcinoma that turned out to be malignant lymphoma by later reinvestigation. After word those lymph nodes disappeared and have not been palpable for about ten months. In October 1987, elevated LDH value, lymph node swelling and gastric lesion were again observed and sixth gastric biopsy demonstrated the picture of malignant lymphoma. He was treated with anti-lymphoma drugs. After his partial remission, he died of gastrointestinal bleeding in April 1988. Specimens of both first lymph node biopsy and sixth gastric biopsy were examined with cell markers for infiltrated cells and were positive for Ki-1/Ber-2H. His final diagnosis was Ki-1 lymphoma.

[Atypical chronic myeloproliferative disorder with translocation (12;13) (p13;q12) and tumor formation].

A 49 year-old man was admitted to our hospital in May 1989, with a cervical tumor and leukocytosis. He had been pointed out leukocytosis for last two years. Peripheral blood examinations demonstrated an increase of leukocytes (39,500/microliters) with low neutrophil alkaline phosphatase, eosinophilia and immature cells. Examination of bone marrow revealed normoplasia with 5.6% eosinophils, 1.4% myeloblasts, 2.6% promyelocytes and 250/microliters megakaryocytes. Cytogenetic analysis disclosed 46, XY, t (12;13) (p13;q12). Southern blot analysis showed no BCR rearrangement. The tumor cells had infiltrated the lymph nodes. Pathological finding agreed with the specimen of the lymph node as in the clot section of bone marrow. He was diagnosed as having a chronic myeloproliferative disorder with tumor formation and was treated with anti-leukemia drugs, including BH-AC, THP, VDS, MTX, VP-16, BUS, 6MP and uvenimex. He showed hematological remission, temporary, but he did not reach cytogenetical remission and died in April 1990. Further study in a large series is necessary to define whether the abnormality of the chromosome with t(12;13) (p13;q12) is characteristic in cases with tumor formation.

[An autopsy case of IgE myeloma].

An autopsy case of IgE myeloma, 85-year-old male is reported. He was admitted to our hospital on November 17, 1987 due to pain of left humerus. Osteolytic and osteoporotic foci were found in left humerus, ribs, spinal column and femurs. Complete blood countings were as follows: RBC 3.23 x 10(12)/L, Hb 11.3 g/dl, WBC 6.3 x 10(9)/L, platelet 173 x 10(9)/L. Blood smear showed red cell rouleaux formation without myeloma cells. Examination of bone marrow revealed hypoplasia with 52% myeloma cells which were stained with anti-IgE and antilambda antisera by peroxidase anti-peroxidase method. Total serum protein level was 7.7 g/dl. Monoclonal protein was observed at fast gamma-region by cellulose-acetate electrophoresis. On immunoelectrophoresis, this monoclonal protein made specific M-bow against anti-IgE and anti-lambda antisera. The IgE level in serum and urine were 7.8 x 10(6) IU/ml and 2.4 x 10(3) IU/ml by radio-immunoassay respectively. He was died owing to renal failure on September 7, 1988. Postmortem examination showed infiltration of myeloma cells in bone marrow, spleen, kidneys, lungs and generalized lymph nodes.

Serial studies on in vitro colony formation in patients with acute leukemia in relation to the maintenance of remission.

For the purpose of preventing a relapse of acute leukemia which is currently the major problem in the successful treatment of the disease, repeated consolidation or intensification therapy during the first year following remission is important. To evaluate these therapies, we investigated the serial changes in CFU-C's of the marrow cells from 12 patients with acute nonlymphocytic leukemia in remission and tried to estimate the relationship between the intensity of consolidation or intensification therapy and the duration of remission, utilizing the degree of reduction in CFU-C's seven days after these treatments as an indicator. As a result, after 21 out of 22 courses of therapy where CFU-C's were reduced significantly after the therapy, the patients were still in remission at the time of the next intensificiation therapy (at most for about 100 days). On the other hand, after five out of ten courses where CFU-C's were not reduced significantly, the patients were in relapse at the time of the next intensification therapy. From these results, it may be inferred that cases whose CFU-C's are not reduced significantly should be treated intensively again within a short period.

Influence of leukaemic cells on the colony formation of human bone marrow cells in vitro II. Suppressive effects of leukaemic cell extracts.

The influence of leukaemic cells on the colony formation of human bone marrow cells was studied in vitro as an extension of our previous work (Chiyoda et al., 1975). An extract of leukaemic bone marrow cells significantly suppressed colony forming ability of the normal bone marrow cells, whereas an extract of normal bone marrow cells did not suppress it except in two cases. The suppressive effect of normal bone marrow cells, however, was obviously less intense than that of leukaemic cells. This suppressive effect was dose dependent and was fairly stable to heat treatment. These results suggest that leukaemic bone marrow cells contain factor(s) which suppress normal colony formation.

Colony-forming cells in culture and colony-stimulating activity of the urine and the serum in a case of cyclic neutropenia.

A 22-year-old female with cyclic neutropenia was studied. Her bone marrow cells showed high colony-forming activity in soft agar through the cycle, though there were slight fluctuations in the number and the shape of colonies. On the other hand, the peak of urinary colong-stimulating activity (CSA) occurred at the neutropenic stage. The dialyzed serum showed two peaks of CSA, i.e., at the peak and the valley of the neutrophil count, although the undialyzed serum showed only one peak at the neutroenic stage. It is suggested on the basis of these data that humoral factors may play a role in maintaining the neutrophil cycle.

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.